A Mediterranean-style diet is a healthy eating pattern that may benefit cancer risk, but evidence among Americans is scarce. We examined the prospective association between adherence to such a diet pattern and total cancer risk. A Mediterranean-style dietary pattern (MSDP) score was derived from a semi-quantitative food frequency questionnaire at exam 5 (1991–1995). Subjects included 2966 participants of the Framingham Offspring Study who were free of prevalent cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle, and anthropometric measures. Cox-models were also used to examine effect modification by lifestyle and anthropometric measures. During 18 years of median follow-up, 259 women and 352 men were diagnosed with cancer. Women with moderate or higher adherence to the MSDP had ≥25% lower risks of cancer than women with the lowest MSDP (HR (moderate vs. lowest): 0.71, 95% CI: 0.52–0.97 and HR (highest vs. lowest): 0.74; 95% CI: 0.55–0.99). The association between MSDP score and cancer risk in men was weaker except in non-smokers. Beneficial effects of the MSDP in women were stronger among those who were not overweight. In this study, higher adherence to MSDP was associated with lower cancer risk, especially among women. The American Institute for Cancer Research 2018) report 8 report ,4,5. TheFor nearly three decades, epidemiologic evidence has supported the health benefits of adherence to a Mediterranean diet in the primary and secondary prevention of non–communicable chronic diseases ,7,8. AltMediterranean diet studies sometimes differ in the means by which the diet pattern is scored. Many studies, including EPIC, have used a Mediterranean diet score based on whether the participant had higher or lower intakes of the relevant foods and nutrients, defined as being above or below the sex-median intakes in that population . BecauseThe primary aim of this prospective study was to examine the longitudinal association between adherence to the MSDP and total cancer risk in the Framingham Offspring Study (FOS) cohort. We examined whether this association was modified by anthropometric measures of body fat or lifestyle factors. In secondary analyses, we assessed the association between each food group considered in the MSDP and total cancer risk. n = 362); (b) history of cancer or prevalent cancer except non-melanoma skin cancer (n = 147); (c) aged less than 30 years at baseline (n = 4); and (d) missing covariates (n = 233). The Framingham Offspring Study data collection and these analyses were approved by the Institutional Review Board of Boston University School of Medicine (Protocols H-32086 and H-32132).In 1971, 5124 individuals were enrolled in the prospective FOS. The participants were the children of those who were part of the original Framingham Heart Study. The examination visits, starting with exam 2, were carried out at approximately 4-year intervals . Food frDiet data was assessed by self-report using a semi–quantitative food frequency questionnaire (FFQ) . The FFQThe scoring methods for the MSDP score were based on adherence to a traditional Mediterranean diet  and haveThe primary occurrence of cancer was adjudicated using a standardized Framingham Study protocol as previously described . Briefly2).Height and weight were measured with a standard beam balance scale with the subject wearing a hospital gown and no shoes . To reduPhysical activity was assessed at exams 4 (1987–1991) and 7 (1998–2001) using self-report questionnaires that included recreational activities and household work. The intensity levels for light, moderate, and vigorous activities were derived from previous studies of oxygen utilization for a given level of activity. A weighted moderate and vigorous activity score was calculated by summing total hours of moderate activity  and total hours of vigorous activity (multiplied by its intensity score) . The number of years of education was self-reported at exam two and was used to classify baseline education level into three categories: high school or less, some college, and college or graduate degree. Missing education data at exam two were imputed hierarchically as follows: education level at exam 8 (2005–2008), median years of education level for the subjects with the same occupation at exam 7 (1998–2001), and sex-specific median years of education at exam 2 (1979–1983). Missing data for self-reported pack-years of cigarette smoking at exam 5 (1991–1995) were substituted with the mean of pack-years from exams 4 (1987–1991) and 6 (1995–1998) when available. Other self-reported covariates at exam 5 (1991–1995) included: multivitamin use, other supplement use, cigarette smoking status , energy intake, and alcohol intake (g/day). Measures of abdominal adiposity, including waist circumference (cm) and waist–to–height ratio , were also collected at baseline. Further, we created a time-dependent variable to reflect self-reported estrogen use (including estrogen use only). We classified women as never or ever users of estrogen based on self-report across multiple exam visits. Type 2 diabetes was defined at baseline when the participant met one of the following criteria: (a) 10-hour-fasting glucose of ≥126 mg/dL; (b) non-fasting glucose of ≥200 mg/dL; (c) confirmed treatment of diabetes, or (d) self-reported diagnosis of possible diabetes at one visit with a subsequent diagnosis of definite diabetes at the next exam (in the absence of an excessive weight gain of 7% or more of body weight).Sensitivity analyses were based on the exposure distribution and power considerations and used to explore different cut-off values for categorizing the MSDP score. The optimal classification was selected as follows: low: 4.0–19.0 (reference group), moderate: 19.1–25.0, and high: 25.1–50.9. Incidence rates for total cancer were computed by dividing the number of cancer cases by total person-years (py) of follow-up calculated from baseline  to the first of the following events: primary occurrence of cancer, loss to follow-up, date of last exam or death. Age and multivariable-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer. A test for linear trend across MSDP score categories was performed. 2 for women and <30 vs. ≥30 kg/m2 for men [Because the effects of adherence to the MSDP may depend on the level of other lifestyle and anthropometric measures, we chose to assess interaction between MSDP adherence and each of the following risk factors: BMI, WHtR, alcohol intake, and cigarette smoking status. To better assess public health importance, interaction was assessed on an additive rather than a multiplicative scale ,27. Cox- for men ,23. The  for men . Three c2), cigarette pack-years, physical activity , prevalent diabetes, and supplement use (never vs. ever). Factors not included in the final models were educational level, alcohol intake, and estrogen use because they were not found confounding the association between MSDP adherence and total cancer risk. The final multivariable models adjusted for confounders that were found to alter the age-adjusted hazard ratios by approximately 10% or more in men and women separately. Those factors retained in the final models included BMI , moderate, or high for each food group. The multivariable Cox models included the same factors listed above plus total energy intake; these models also mutually adjusted for the intakes of all other MSDP score components. A test for linear trend across each food group was performed based on the category-specific medians of food intake. No violations of the proportional hazard assumptions were found in any of the models. The statistical analyses in this study were conducted using SAS statistical software, version 9.4 .The MSDP score at baseline was normally distributed, with a mean of 22.4 (± 7.3) (range 4.0–51.0). moderate: 0.85, 95% CI: 0.70–1.04; HRhigh: 0.84, 95% CI: 0.68–1.03). In sex-stratified analyses, greater adherence to a Mediterranean diet had a much stronger beneficial effect on total cancer risk in women than in men. For women, those in the moderate and higher MSDP score categories had 29% (95% CI: 0.52–0.97) and 26% (95% CI: 0.55–0.99) lower cancer risks than those in the lowest MSDP score category. Of the 2966 men and women at baseline, 611 subsequently developed cancer . OverallWe also explored possible effect modification on an additive scale of the MSDP scores by cigarette smoking and alcohol consumption. Non-smoking and former-smoking women generally had lower cancer risks, and these associations were slightly stronger among those with higher MSDP scores. In men, we found that those with higher MSDP scores who were non-smokers had the lowest risk of cancer . Once again, while these effects were more than additive, the estimated interaction did not reach statistical significance (p-interaction > 0.05). Finally, there was no consistent evidence of effect modification by alcohol intake in either men or women. This is the first long-term population-based study using the MSDP score developed by Rumawas et al.  to assesOnly two previous studies have reported beneficial effects of the Mediterranean diet on total cancer incidence ,15. The Our results suggested a stronger risk reduction in Framingham women than was observed in the larger EPIC study . It is pA separate analysis of data from the Greek cohort in the EPIC study found that adherence to a Mediterranean diet was associated with a statistically significant 22% lower risk of cancer overall, with stronger effects found among women  than among men, who had a non-statistically significant 17% lower risk . It is pExcess body fat, including overweight, obesity, and weight gain (during middle adult years), are strong modifiable risk factors for certain cancers such as breast , colorectal, and reproductive cancers ,29. The In this study, the beneficial effect of a higher MSDP score in men was strongest among never-smokers, while in an earlier EPIC study, the beneficial effects of a Mediterranean-style diet were slightly stronger among current smokers than past or never smokers . It is pAn analysis of each food group considered in a Mediterranean diet score in association with total cancer risk has only been done once before. Our results showed that there was some tendency for certain food groups to be associated with lower cancer risks, especially in women, but none had statistically significant linear trends. In the earlier EPIC study, there was no evidence of an association between any individual component of the Mediterranean diet score with risk of total cancer . The canIn addition, the beneficial effects of the Mediterranean diet could be explained by intermediate effects on body fat or body composition resulting from the obesity-protective effect of the Mediterranean diet ,10,39. DThe strengths of this study include its prospective design with carefully adjudicated cancer outcomes using standardized procedures . In addiThis is the first prospective cohort study to show that consumption of a Mediterranean-style diet may be one effective strategy for reducing total cancer risk in the US. In this study, the cancer-protective effects of higher Mediterranean diet adherence were strongest in women with less adiposity and among men who did not smoke. Given the high rates of cancer in the US ,45, thes


We recently developed an oncogenetic model to overcome the unprecedented demand for genetic counseling and testing for hereditary breast and ovarian cancer. Quality and performance indicators showed that the implementation of this model improved access to genetic counseling and minimized delays for genetic tests for patients, who reported to be overwhelmingly satisfied with the process. However, it remains unknown whether this model is robust and sustainable or requires adjustments. In addition, whether the model could be deployed elsewhere remains also to be elucidated. The C-MOnGene study was therefore designed to gain an in-depth understanding of the context in which the model was developed and implemented, and document the lessons that can be learned to optimize oncogenetic services delivery in other settings.Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics. BRCA1 or BRCA2 genes are the most common cause of HBOC, and variant carriers have a 5- to 20-fold increased risk of developing breast or ovarian cancer [BRCA1 and 69% for BRCA2 pathogenic variant carriers [It has been estimated that highly penetrant hereditary cancer syndromes account for up to 10% of all cancer incidence worldwide , they ten cancer ,8. The pBRCA pathogenic variant status can inform surgical management for breast cancer patients, with more radical surgery considered to be an effective treatment in variant carriers, who are at increased risk of subsequent cancer [BRCA pathogenic variant carriers. Indeed, although platinum-based therapies are not the standard of care for breast cancer, they can have utility in carriers of pathogenic mutations in BRCA1 and BRCA2 genes, who are particularly sensitive to platinum-based drugs [BRCA1 or BRCA2 pathogenic mutations directly or via their pathways are increasingly available for ovarian and breast cancer patients who are carriers of such variants [Knowledge of t cancer . This ined drugs . Newer evariants .BRCA1 and BRCA2 testing for cancer risk reduction in breast and ovarian cancer is well-established [BRCA1 or BRCA2 pathogenic variants. Bilateral mastectomy has been shown to decrease the risk of breast cancer by approximately 90% [BRCA1 pathogenic variant carriers [The value of ablished ,13,14. Ctely 90% ,16. For tely 90% ,18,19. Ctely 90% ,21. Addicarriers .BRCA1 or BRCA2 pathogenic variant allows for targeted screening, prevention, and treatment, and can be lifesaving, several international guidelines recommend genetic testing for these genes within the set of possible genetic variants for individuals or patients suspected of being at risk of breast and ovarian cancer [BRCA1 and BRCA2 pathogenic variants for breast and ovarian cancer in the medical biology procedures directory [Recognizing that the identification of individuals at risk of carrying a n cancer ,13,23. Iirectory . In theoMedical genetic services in the province of Quebec, as in many other Canadian jurisdictions and countries, are facing an unprecedented demand for genetic counseling (GC) and genetic testing (GT) for HBOC, a demand that exceeds the systems’ current capacity ,26. Of sOne could say that an easy solution might be to recruit more staff, particularly genetic counselors. However, in Canada, there are five graduate programs for genetic counselors, which cumulatively generate approximately 20–25 new genetic counselors per year. Among these students, 4–6 are from the province of Quebec , and 50%In light of increasing imbalance between the supply and demand for genetic counseling and testing for HBOC, alternative models of genetic service delivery have been called for ,35,36,37After a preparatory phase between 2015 and 2016, the COM was implemented in 2017, and has been continuously updated, when needed, to preserve its flexibility. Globally, the model has improved the delivery of oncogenetic services to breast and ovarian cancer patients and high-risk healthy women through a reorganization of existing resources and expertise. As shown in In addition, as shown in p values of all paired t-tests < 0.001), which is consistent with patients’ satisfaction with the process.Finally, these data also showed that group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics. As shown in The COM has been developed and implemented through a natural emergent mechanism  stemmingThe overarching aim of C-MOnGene study is to gain an in-depth understanding of the context in which the COM was developed and implemented, and document the lessons that can be learned from it to optimize local and regional oncogenetic services delivery in Quebec and elsewhere. Our hypothesis is that a dynamic and complex interplay of contextual factors , actors  and culture  influenced the development and implementation of the COM. We also hypothesize that each site involved in delivering oncogenetic services will experiment its unique interplay of factors. Our research will be guided by the following specific questions (RQ):RQ1: What general and specific factors influenced the development and implementation phases of the COM, and what adjustments are still required to further enhance its performance?RQ2: Which components of the COM could be adopted, in what types of settings, and what are the critical barriers and facilitators?RQ3: What are the social (acceptability), economic, legal, and regulatory implications of implementing the COM?RQ4: What can be derived for future planning and implementation of new (or adapted) genetic health services in oncology settings?Our hypothesis is that a dynamic and complex interplay of contextual factors , actors  and culture  influenced the development and implementation of the COM. We also hypothesize that each site involved in delivering oncogenetic services will experiment its unique interplay of factors.Our research will use a multiple case study design  with mixTo guide our methodological choices, including data collection and analytical approaches, we will rely on two complementary conceptual frameworks to answer our research questions. The first is the diffusion of innovations theory developed by Rogers ,42. This2. The three other settings  are health and social services integrated centers called CISSS and CIUSSS (depending on university affiliations) which include hospitals, primary care and community services. These three settings deserve populations varying between 197,000 people and 428,000 people for land areas varying between 15,000 and 95,700 km2.In agreement with the research questions and the objective of examining the potential adoption of the COM components in a variety of settings with distinct clinical missions, population structures and needs, medical facilities and healthcare human resources, our research activities will be conducted in four settings. Setting 1 is where the COM was initially developed and has run successfully since 2017. This setting is part of a network of five University-affiliated hospitals, which constitutes one of the three largest university hospital centers in Canada deserving nearly two million people for a land area of 18,600 kmRQ1: What general and specific factors influenced the development and implementation phases of the COM, and what adjustments are still required to further enhance its performance?To identify the events and processes that led to the development and implementation of the COM at Setting 1, we will start by reviewing pertinent documents, including meeting minutes, action plans, internal notes, and annual reports. A series of one-to-one semi-structured interviews will be conducted with key informants, including members of the interdisciplinary team who initiated the model, medical directors of the breast cancer clinic and gynecologic oncologic division, and front-line managers of the oncology and genetics clinical divisions. Purposive sampling will be used to identify these informants, with snowball sampling used to further include individuals involved in the COM. The interviews will explore external and internal factors underlying the development of this model. We will also explore experiences, barriers and challenges related to its development and the conditions in which the activities have been delivered . Discussions will also concern the sustainability of these activities, potential areas of concern, and the need (or not) for adjustments. We will also seek patients’ perspectives regarding the model. Patients who consented to group counseling and those who accepted the genetic test since the model’s inception will be asked to fill the validated French version of the decision regret scale (5 items) . They wiRQ2: Which components of the COM could be adopted, in what types of settings, and what are the critical barriers and facilitators?To address this question, we will first undertake an environmental scan of all four sites to assess the current state of their clinical cancer genetic services. Thus, demographics, number of patient referrals to general and more specific cancer genetic resources, number of patients seen over the last 12 months, dedicated genetics resources, referrals and scheduling processes, resources and funding, and documented policy for identifying and managing urgent cases will be extracted through medical charts (databases and/or spreadsheets). Responses to a dedicated questionnaire addressed to genetics departments or health professionals dealing and/or overseeing genetics services delivery will also serve to that purpose. Second, an open-ended questionnaire accompanied by a summary of key elements of the COM  will be addressed to medical oncologists, geneticists and genetic counselors, nurse navigator and clinical nurses, and front-line managers of Settings 2, 3, and 4 to gather their opinions, beliefs, and feelings about the COM. They will also be questioned on whether the model or some of its components could be implemented in (or adapted to) their setting in addition to related challenges, opportunities, threats, and mitigation strategies. Specific important issues that will need to be addressed concern the involvement of non-genetic health professionals in the provision of genetic services, the collaboration with geneticists and genetic counselors, and training issues. A gap analysis between the model requirements and the current situation at each site will be conducted. Using a gap analysis template, the analysis will focus on identifying the difference between current state  and the future state . Focused discussions will be organized at each site to present the results for validation and consolidation and to collaboratively define next steps and proposals.RQ3: What are the social, economic, legal, and regulatory implications of implementing the COM?Acceptability (concerns and barriers) from the professionals’ perspective about an extension of the role of non-genetic health professionals will be examined through focused discussions with genetics and associated health care providers from all of the four settings. Our discussion grid will be developed based on responses obtained from the open-ended questionnaire (RQ2). Acceptability (concerns and barriers) from the patients’ perspective collected at Setting 1 will be assessed by comparing the number of those who, for example, attended group counseling to those who attended individual counseling and comparing their level of satisfaction, decision regret and, when available, their usage of screening and risk-reduction strategies. A scoping review  will be RQ4: What can be derived for future planning and implementation of new (or adapted) genetic health services?Lessons learned from this research, particularly in terms of recommendations to improve genetic and oncogenetic service delivery, will be operationalized through an invitational stakeholders’ workshop and the instigation of a clinical advisory committee (CAC) who will lead the validation of recommendations. Members of our research team organize a biannual symposium on hereditary cancer risk titled “Symposium Risque Héréditaire de Cancer,” and it is attended by more than 200 researchers, health professionals, decision makers, and patients. The workshop will be held a day before the next symposium planned in October 2021 or later depending of the situation related to the COVID-19 pandemic. The workshop participants will be determined by the research team and will include a diverse group of researchers, healthcare providers, managers, decision-makers, patient partners, and trainees with various profiles. Before the workshop, syntheses of relevant literature on the integration of innovation and collaborative models for service delivery, drawing on the methodological approach by McMaster Health Forum , will beAll qualitative data will be retained as written or electronic files, including document summaries, open-ended questionnaire responses, and interviews and group discussion transcripts. Interviews and group discussions will be recorded and transcribed verbatim. Thematic analysis will be used to systematically analyze all qualitative data  using NVWe sought here to present the protocol of the C-MOnGene study, designed to improve our understanding on how a novel collaborative oncogenetic model for genetic counseling and testing for HBOC was developed, performs, and could be integrated in different settings. We also presented quality and performance indicators that prompted us to develop this protocol. Indeed, these data suggest that implementing the model enabled clinical teams to provide more consultations and decrease the average number of days between counseling and disclosure. However, more in-depth analyses of these findings are required since historical changes have occurred and are occurring at a fast pace in the field of genetics in areas such as recommendations, access and turnaround time get results ,54,55.The demand for oncogenetic services has increased in recent years in the context of limited resources, resulting in dramatic increases in delays for genetic counseling and testing for high-risk healthy women and breast and ovarian cancer patients. It is recognized that failure to identify individuals with a higher risk of carrying pathogenic variants for HBOC represents missed preventive and therapeutic opportunities. Like many other jurisdictions around the world, precision medicine has been identified as one of two cross-cutting niches leading the province of Quebec’s life sciences strategy 2017–2027 . PrecisiThis study protocol has been examined by the Research Ethics Board of the CHU de Québec-Université Laval. The Board waived the ethics approval requirement since the study’s purpose is to evaluate the quality of services already in place at the institution.In order to maximize the quality and impact of deliverables, our project includes an integrated knowledge translation strategy . A widel


Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case–control study (1992–2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high  versus medium–low adherence to the DRRD was 0.73 . Similar results were observed after the exclusion of diabetic women  and allowance for total vegetable consumption . Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 . Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention. Endometrial cancer arises predominantly in post-menopausal women . Risk faSeveral studies found an increased risk of endometrial cancer in women with diabetes ,15,16,17Diet may impact endometrial cancer independently from obesity, but the exact underlying mechanisms remain poorly understood . Coffee Diet is known to influence insulin resistance and hyperinsulinemia. Along this line, a dietary pattern for diabetes mellitus prevention (the diabetes risk reduction diet (DRRD)) was recently proposed . The oriIn the present investigation, we assessed the association between adherence to the DRRD and the risk of endometrial cancer using data derived from a multicentric Italian study.We retrieved data from a multicentric case–control study on endometrial cancer carried out between 1992 and 2006 in three Italian areas, i.e., the metropolitan area of Milan, the provinces of Udine and Pordenone in northern Italy, and the urban Naples area in southern Italy ,42. The Cases were women with a diagnosis of endometrial cancer, histologically confirmed, according to the International Classification of Diseases , hospitalized in the major university and general hospitals of the study areas. Women diagnosed with an endometrial cancer up to a year earlier and with no previous cancer at any site were eligible. Controls, enrolled in the same network of hospitals as cases, were women admitted for a wide spectrum of acute and non-neoplastic illnesses: traumas (36%); other orthopedic disorders (32%); acute surgical conditions (9%); and miscellaneous illnesses including eye, nose, ear, or skin disorders (23%). Among controls, we excluded women with a previous history of hysterectomy or those hospitalized for hormone-related or gynecological conditions, or any clinical condition leading to long-term dietary changes. Over 95% of women approached agreed to take part in the study.Centrally trained personnel interviewed cases and controls during their hospital stay using a standard structured questionnaire, including sociodemographic and anthropometric characteristics, selected lifestyle behaviors , personal clinical information, family (first-degree relatives) history of cancer, menstrual and reproductive factors, and use of OC and HRT.In order to assess the usual diet during the 2 years preceding cancer diagnosis (for cases) or hospitalization (for controls), a valid and reproducible food frequency questionnaire (FFQ) ,44,45 wa2), occupational physical activity , smoking status , alcohol intake , history of diabetes , total energy intake (quintiles derived from controls), age at menarche , parity ), menopausal status , use of OC , and use of HRT . A few missing data on adjustment factors were replaced by the median value (continuous variables) or mode category  according to case/control status.Data analysis. We used logistic regression models to calculate the odds ratios (OR) of endometrial cancer and the corresponding 95% confidence intervals (CI) for high  versus medium–low adherence to the DRRD, as well as for one SD increment in the score. Models were conditioned on center and quinquennia of age and adjusted for years of education , year of interview , BMI  was used as the reference category.All the analyses were performed with SAS software version 9.4 .The characteristics of endometrial cancer cases and matched controls are shown in Inverse associations were observed in most of the subgroups analyzed , with thSingle components of the DRRD score were not significantly associated with endometrial cancer risk, with the exception of a direct association with cereal fiber intake .The OR oIn the current study, a score measuring adherence to a diet developed for diabetes risk reduction was inversely associated with endometrial cancer risk. After adjusting for several possible confounders, including factors related to endogenous estrogen exposure, BMI, and total energy intake, women with a high DRRD adherence score had a 27% reduced risk of endometrial cancer, in comparison to those with a medium–low adherence. The association was attenuated after allowance for vegetable intake (non-significant 20% reduced risk) and was not detected among pre-menopausal women and women who smoked. The null results in those subgroups have to be interpreted with caution given the limited number of pre-menopausal women and current smokers in our study, and may be, in any case, chance findings. Combining high adherence to the DRRD and high vegetable intake was associated with a greater decrease in the risk of endometrial cancer.This is the first study in which the DRRD was examined in association with endometrial cancer. An inverse association of the DRRD with breast cancer ,40, pancEpidemiological evidence on the impact of dietary factors on endometrial cancer risk is largely inconclusive . With reHigh vegetable consumption was consistently reported as protective against endometrial cancer risk in case–control studies ,36,53. TIn the assessment of the association between diet and chronic diseases, the investigation of dietary patterns represents a complementary approach to the analysis of the role of distinct foods or nutrients. The dietary pattern approach allows to take into account the biologic interactions among nutrients. Dietary patterns are particularly useful when the standard method of focusing on individual foods or nutrients does not reveal significant associations . Along tThe relationship between diabetes and endometrial cancer risk has been modulated by insulin and insulin growth factor (IGF) levels, which are likely affected by the DRRD. However, insulin and other anti-diabetic drugs have not been consistently associated with the risk of endometrial cancer .trans fats in Italian foods is not available from food composition tables, therefore we could not include it in the DRRD score [There are strengths and weaknesses of our study. Generally, case–control studies are more prone to selection and information bias when compared to cohort studies. However, the almost complete participation of elected women and the exclusion from the control group of women admitted for hormone-related or gynecological conditions, or any medical condition leading to long-term dietary changes weigh against a major role of selection bias in the present study. Moreover, the recruitment areas were similar for cases and controls. Further, in the carcinogenesis of endometrial cancer, estrogens, obesity, and the metabolic syndrome seem to act on the later stages of the carcinogenic process. Along this line, a reduction in the risk of endometrial cancer was observed shortly after bariatric-surgery-induced weight loss . Case–coRD score . The majRD score ,44,45, aIn conclusion, this study suggests that high adherence to a diabetes prevention diet is inversely related to endometrial cancer risk. Combining such a diet with high vegetable intake may provide additional benefit in endometrial cancer prevention.


Background: DNA methylation is influenced by environmental factors and contributes to adverse modification of cancer risk and clinicopathological features.Methods: A case-control study  was conducted to evaluate the effect of environmental factors and OPRM1 methylation in peripheral blood leukocyte (PBL) DNA on the risk of breast cancer. A case-only study (373 cases) was designed to evaluate the effects of environmental factors on OPRM1 methylation in tumor tissue and the relationship of methylation with clinicopathological features.Results: We found a significant association between hypermethylation of OPRM1 and the risk of breast cancer . OPRM1 hypermethylation in PBL DNA combined with low intake of vegetable, garlic, soybean, poultry, and milk; high pork intake; less regular sports and a high psychological stress index significantly increased the risk of breast cancer. Soybean intake  and regular sports  were associated with OPRM1 hypermethylation in tumor DNA. OPRM1 hypermethylation in tumor tissue was correlated with estrogen receptor (ER)  and progesterone receptor (PR)  negative status; in addition, OPRM1 hypermethylation in PBL DNA was associated with human epidermal growth factor receptor 2 (HER-2) negative status .Conclusion: A healthy diet, psychosocial adaptability, and regular sports are very beneficial for breast cancer prevention and progress, especially for OPRM1 hypermethylation carriers. Personalized treatment considering the correlation between OPRM1 hypermethylation and ER and PR status may provide a novel benefit for breast cancer patients. Breast cancer is one of the most common public health issues among women . AccordiBreast cancer is a heterogeneous disease with distinct genetic, epigenetic and histopathological characteristics . DNA metDNA methylation can be altered by environmental factors, which in turn affect breast cancer risk . TobaccoOPRM1) gene encodes the mu opioid receptor (MOR), one of three opioid receptors in humans , behavior , menstrual and reproductive history, etc. The clinical and pathological information of cancer patients was extracted from medical records, including the TNM stage, histological records, and other pathological results. We did our best to obtain a complete questionnaire from each participant, but there were still some subjects who did not answer individual questions. Therefore, the DNA was extracted from blood samples and <25 mg of minced tumor tissues using the QIAamp DNA Blood Mini kit  and PureLinkTM Genomic DNA Kit , respectively. All steps were performed in accordance with the manufacturer's protocol, and purified DNA was stored at −80°C as soon as possible. Bisulfite conversion was performed according to the manufacturer's guidelines using 2 μg of DNA and the EpiTect Bisulfite Kit . Before and after the transformation process, the amount of DNA was determined using a Nanodrop 2000 spectrophotometer . The transformed DNA was also immediately stored at −80°C.7 copies of plasmid DNA were used to construct a standard curve for quantification.According to the manufacturer's instructions, the TOPO TA Cloning for Sequencing kit  was used to transfer freshly purified, target-region-specific PCR products to TOP10 competent cells for cloning . The extDNA methylation was measured by quantitative methylation-specific PCR technology (qMSP). Bisulfite-treated DNA from each specimen served as the template, and qMSP was performed with iTaq Universal SYBR Green Supermix  and ABI 7500 real-time PCR amplifier  while strictly following the operating protocols.OPRM1: forward primer, 5′-CGGTTATTTATCGTTTGTAGGAGGAAACG-3′ reverse primer; 5′-ATCCAACAACGCTTCTATTCGAATCCG-3′. The internal reference was designed as follows: housekeeping gene (MyOD), forward primer, 5′-CCAACTCCAAATCCCCTCTCTAT-3′; reverse primer, 5′-TGATTAATTTAGATTGGGTTTAGAGAAGGA-3′.Primers were designed for qMSP analysis using Primer Premier 5.0 software as follows: OPRM1, 6 min at 95°C, followed by 42 cycles of 95°C for 30 s, 58°C for 30 s, and 72°C for 30 s and (2) MyOD, 6 min at 95°C, followed by 42 cycles of 95°C for 30 s, 56°C for 30 s, and 72°C for 30 s. All the procedures were performed in duplicate, and 10–20% of the samples were redetected in our study.For the amplification, 1 μl bisulfite converted DNA (5 ng) was added to 19 μl amplification Master Mix containing 10 μl SYBR Green Supermix, 0.6 μl of forward and reverse primer, and 7.8 μl RNAse-free water. The reaction protocol was as follows: (1) The specific of amplification products were determined with melting curve analysis according to fluorescence data acquired during dissociation steps. Each sample's methylation level was calculated by the following formula: Methylation level = (quantity of target gene/quantity of housekeeping gene) × 100%.t-test, respectively. Univariate and multivariate logistic regression analysis were used to calculate the crude and adjusted odds ratio (ORs) and 95% confidence interval (95%CIs). Combined and interaction effects were performed by crossover analysis  was 53.218%. The signals of samples were compared to the standard curve. We constructed a standard curve using a 10–10P = 0.040), educational level (P = 0.001), occupation (P = 0.000), and family history of cancer (P = 0.000). Therefore, these characteristics were adjusted as confounding factors in the following analyses. As shown in OPRM1 in PBL DNA and the risk of breast cancer .A total of 402 PBL DNA samples from breast cancer patients and 470 control samples were analyzed. The distribution of basic demographic characteristics is shown in P < 0.05). Intake of vegetable, garlic, poultry, milk, and soybean and regular sports are protective factors against breast cancer (P < 0.05). Subsequently, those environmental factors identified as significant were examined in the multivariate analyses. The results showed that vegetable intake , garlic intake , poultry intake , milk intake , regular sports , and soybean intake  were significantly associated with a decreased risk of breast cancer. A high intake of pork  and a high psychological stress index  were significantly associated with an increased risk of breast cancer.Univariate and multivariate logistic regression were used to analyze the relationship between environmental factors and breast cancer risk. As shown in OPRM1 hypermethylation and low vegetable intake , garlic intake , soybean intake , poultry intake , milk intake , and less sports  were observed to be significantly related to increased breast cancer risk. In addition, we also found a significant combination of OPRM1 hypermethylation and a high pork intake  and high psychological stress index  for increased breast cancer risk. There was no significant interaction between OPRM1 hypermethylation and any environmental factor in breast cancer.As shown in P > 0.05) between the OPRM1 hypermethylated group and the hypomethylated group was observed.A total of 373 patients with breast cancer were included in this analysis. The basic demographic characteristics for the hypermethylated and hypomethylated groups are shown in OPRM1 hypermethylation in tumor tissue DNA. After introducing these variables into a multivariate model, the soybean intake  and regular sports  were still significantly associated with OPRM1 hypermethylation , soybean intake , and regular sports  are significantly related with hylation .OPRM1 methylation in breast tumor tissue DNA and PBL DNA is shown in OPRM1 hypermethylation in tumor tissue DNA was significantly correlated with ER status  and PR status . In addition, OPRM1 hypermethylation in PBL DNA was significantly associated with HER-2 negative status . No significant relation between OPRM1 hypermethylation in either tumor tissue DNA or PBL DNA with the TNM stage, pathological type, tumor invasion status, lymphnode involved, metastasis status, histological type or P53 expression was found.The relationship between clinicopathological characteristics and OPRM1 methylation and breast cancer. First, we found that OPRM1 hypermethylation in PBL DNA increased the breast cancer risk. Furthermore, OPRM1 hypermethylation combined with low intake of vegetable, garlic, soybean, poultry, and milk; less regular sports; and a high pork intake and high psychological stress index significantly increased the risk of breast cancer. We also found that soybean intake and regular sports reduced OPRM1 methylation in tumor tissue. Additionally, OPRM1 hypermethylation in tumor tissue DNA was significantly correlated with ER and PR negative status, and hypermethylation in PBL DNA was significantly associated with HER-2 negative status.Accumulating research has shown the importance of DNA methylation in the impact of environmental factors on breast cancer risk, and this epigenetic mechanism is also associated with specific clinicopathological features . In thisOPRM1 hypermethylation in PBL DNA increased the breast cancer risk with a strong correlation . Guerrero-Alba et al.  combined with OPRM1 hypermethylation in PBL DNA increased breast cancer risk with a strong association . Arida et al. . All of these results suggest that regular sports can not only reduce the risk of breast cancer directly but also indirectly change the individual's susceptibility to breast cancer through modification of DNA methylation.Steensberg et al.  reporteda et al.  randomlyP < 0.05). Vegetables are rich in dietary fiber, which may decrease reabsorption in the gut of estrogen excreted in the biliary system (OPRM1 hypermethylation in PBL DNA was observed in our study to be significantly associated with an increased risk of breast cancer (P < 0.05). Therefore, we also encourage that women with OPRM1 hypermethylation should increase their intake of vegetable, garlic, milk and poultry and reduce their intake of pork to prevent breast cancer.In addition, many dietary factors are also related to breast cancer risk . We founy system . Garlic y system . Milk isy system  found thy system . Howevery system . A combiOPRM1 hypermethylation increased the risk of breast cancer . Moreover, soybean intake reduced OPRM1 methylation in tumor tissue . However, Katrin Sak reviewed the existing literature and reported that intake of isoflavones can be associated with a decrease in breast tumorigenesis only in Asian countries where the consumption of soy foods is high but not among Western women with significantly lower ingestion amounts . As Dunnwald et al.  should be encouraged with the consideration of the correlation between OPRM1 hypermethylation and ER/PR, HER-2 negative status in breast cancer.This study identified that The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Human Research and Ethics Committee of Harbin Medical University. The patients/participants provided their written informed consent to participate in this study.FW contributed to the study design. LL and SL contributed to methylation detection, data analysis, and drafting the manuscript. NZ contributed to data analysis. SQ, JD, YC, and CW contributed to data collection. YG, ZH, and YY contributed to data interpretation. YZ contributed to manuscript revision. All authors contributed to the article and approved the submitted version.This work was supported by grants from National Nature Science Foundation of China (Nos. 81202262 and 81773503), Postdoctoral Science Special Foundation of China (2013T60390), and Dr. Wu Lien-teh Science Foundation of Harbin Medical University (WLD-QN1106).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Evidences which prove relation between breastfeeding women and risk of breast cancer have been limited.  A meta-analysis was carried out on the basis of published literature from clinical trials and studies among different parts of the world.  Studies were analyzed and extracted using PRISMA flowchart. RevMan 5.4.1 was used for analyzing the extracted data. Included studies were fully cited texts with complete information about studies, trails conducted for risk of breast cancer, and breastfeeding correlations.  Menarche age, family history, lactation duration, and menopausal status have a strong effect on the risks of breast cancer. Family history studies concluded that for 95% CI, the risk ratio was 2.66 .  Findings have suggested that family history and lactation duration affect the risks of breast cancer. According to the World Cancer Research Fund and American Institute for Cancer Research report from 2007, women's health is benefited from breastfeeding (BF). The reduced number of breast cancer (BC) cases (most common type of cancer found in women) is observed because of BF . Breast These studies suggest a strong link between breastfeeding and breast cancer. The initial frail confirmation of breast cancer incidence is observed by the ecological relationship between the observed trends and the depreciation of breastfeeding among women in different parts of the world. Another indirect trail of science is taken from the early observation of the association between breastfeeding and the delayed return of the period of ovulation throughout the postpartum. This has been reported in the clinical observation and the physiological studies , 5.The risk of breast cancer in women is hypothesized to be reduced by breastfeeding which involves two primary mechanisms: (1) differentiation of breast cells where they are modified to generate milk postpregnancy, thus diminishing the vulnerability of the breast tissues towards carcinogenic effects (estrogens), and (2) breastfeeding causes reduction in the lifetime exposure towards the mitogenic effect of estrogens, thus obstructing the process of ovulation . The secFurthermore, serum concentrations of insulin are also minimized by expressing human milk and breastfeeding. Studies have confirmed that proliferation and antiapoptosis effects in breast tissue are correlated with persistent high serum concentrations of insulin, which can raise serum concentrations of IGF-1 (insulin-like growth factor) . DiffereOur literature search strategy is presented in This investigation was performed using the following MeSH keywords: “breastfeeding”, “breast cancer”, “epidemiological diseases”, “pregnancy”, “breastfeeding duration”, “dose-response”, “exclusive breastfeeding”, and “breast tissues”. The additional records from the relevant researches were subsequently hand-searched for further studies. As we had to limit the analysis to the published data, thus, no further attempts were made to recognize any unpublished works.The irregularity associated with the inclusion elements of the published researches was shortlisted via discussion. The attempts were made to institute communication with the authors of the respective papers. The full set of published works which were identified to be relevant was finalized according to the following inclusion parameters : (i) the study under either case-control or prospective cohort study, (ii) data related to the breastfeeding exposure was used in the analysis, (iii) outcomes mentioned as invasive breast cancer with/without carcinoma in situ (CIS) in comparison to the nonbreast cancer, and (iv) distinct odd ratios (OR) calculating the link between breastfeeding and breast cancer.According to the objective of the given study, the focus of data was to be made towards the woman who had breastfed versus the women who had not. Multiple studies with the following category of data were discarded: (i) duplicate data, (ii) reviews or letters or abstracts or case studies or any published data with missing crucial information, (iii) reports that could not assess breastfeeding and breast cancer, (iv) any editorials or letters or commentary with repeated analysis, (v) studies with improper data of duration of breastfeeding, and (vi) studies consisting unilateral vs. bilateral breast cancer risk.The data for the studies was selected by the help of a standardized method of data extraction by the first author whereas the last author was randomly checked. Basic characteristics of the study like age group, study design, duration of study, and menopausal status were extracted for the outcome studies and meta-analysis. The frequencies of outcomes and exposures were collected from all individual studies. The studies included for the analysis are listed in Using the fixed and random effect model, a combined OR (odds ratio) and RR (risk ratio) was obtained , 15. RevA significant number for risk difference was reported in the case of the control group in comparison to the control group for which the forest plot is shown in Menarche age was also a parameter which was studied for its impact on the cases of breast cancer; thus, the studies with menarche age are listed in The forest plot was drawn for menarche age in the case of both case and control groups where risk ratio was found to be 0.94  .I2) was found to be 51%.The funnel plot is shown in Menarche age with 14-15 yr was also studied where the forest plot is shown in Heterogeneity was found to be 85% thereby showing a significant role of menarche age in cases of breast cancer.Girls with menarche age of 16 years were also studied for both case and control groups. Here, a significant risk ratio of 0.57 was noted with 95% C.I of 0.25 and 1.31. Heterogeneity was found to be 97% as found in the forest plot , and theFamily history of breast cancer was studied as a parameter for finding correlation with the breast cancer cases against the control group. The cases are listed in The risk ratio was found to be 2.66  where the forest plot is shown in Duration of lactation was also studied for studies with ≥24-month duration in both control and case groups as listed in The forest plot for the same is shown in Six studies were considered for the study which were analyzed on the basis of menarche, menopause, age of patient, age of control, total participants in study, lactation durations, family history of cancer, incidences of breast cancer in breastfeeding and nonbreastfeeding women, and duration of lactation. Other factors like hormones, number of pregnancies, still births, and complications in pregnancies were also responsible for inducing effect of health. Risk ratios and odds ratios were analyzed by the help of forest and funnel plots. Family history studies concluded that for 95% CI, the risk ratio was 2.66 . A relation was strongly established between the lactation, duration of lactation, menarche age, and family history and risk of breast cancer.The duration of breastfeeding reduces the risk of breast cancer when compared via meta-analysis to the case that did not breastfeed. Thus, it was recommended that researchers must collect information on duration of breastfeeding to potentially reduce breast cancer cases.


This study aimed to estimate the burden of cancer in Koreans attributable to smoking and alcohol consumption using disability-adjusted life years and population attributable fractions. We estimated the burden of 12 cancers due to simultaneous and independent smoking and alcohol exposure in Koreans aged ≥40 years. In men, the cancer burden attributable to the combined risk factors, smoking alone, and alcohol consumption alone were 9.5, 14.8, and 6.1%, respectively; the corresponding values for women were 1.1, 2.5, and 2.7%, respectively. In men, tracheal, bronchial, and lung cancers were the most common cancer types. The disease burden may have been reduced by 16.8, 32.3, and 4.1% in the absence of the combined risk factors, smoking alone, and alcohol consumption alone, respectively. Our findings suggest that risk factor-based intervention may have the greatest preventative effect for lung cancer among all cancers in men. Our real-world data methodology could provide further evidence-based methods to explore and facilitate effective health promotion interventions for specific target groups and may lay the foundation for the establishment of healthcare services according to population subgroups or regional characteristics. Some diseases are associated with past or present exposure to certain health risk factors; thus, prevention and management of known risk factors are important from a public health perspective. Preventing disease and injury through policies and primary care interventions aiming to improve the control of modifiable risk factors, such as smoking, is a key challenge in public health. Therefore, quantifying the exposure levels of leading risk factors and determining their effects on human health are important research areas to identify the sectors of public health where current efforts are inadequate ,2. To thIn everyday life, it is more common for people to engage in a combination of two or more existing risk factors, rather than only one health risk behavior, for example, active cigarette smoking and high-risk alcohol consumption or a combination of active smoking and obesity. In Korea, 66.0% of men and 43.9% of women aged ≥30 years have at least two combined health risk factors . MoreoveDrinking is a social behavior influenced by various environmental factors such as availability, public policies, and acceptance of alcohol use. In Korea, drinking is characterized by a pattern of going back and forth between social drinking and problem drinking . Owing tSeveral national and international studies have demonstrated that smoking and alcohol consumption are major risk factors for cancer development ,19,20,21The Global Burden of Disease (GBD) study used a standardized and comprehensive methodology to estimate country-specific burden of disease, including mortality rates, attributable to a single health risk factor and a combination of risk factors . SeveralQuantifying the burden of disease attributable to specific risk factors in a comprehensive and comparable way may provide a foundation for public health policy design. To this end, the contribution of risk factors to disease burden can be measured by population attributable fractions (PAFs), which integrate information of “dangerousness” and “prevalence” of risk factors, supporting decision-making on population health protection and disease prevention.Therefore, this study aimed to quantitatively measure the cancer burden attributable to smoking and alcohol consumption in Koreans by analyzing domestic data sources. In addition, to provide further information for formulating broader and more meaningful prevention strategies, the combined effect of the two health risk behaviors was evaluated.Smoking and alcohol consumption were analyzed separately and as combined risk factors. In addition, based on previous meta-analyses ,13,14,15To investigate cancer burden in Korea, the number of DALYs for cancers in Koreans aged ≥40 years as of 2018 was calculated. This included calculating the following components using the most recent KNBD measurement methodology: years of life lost (YLLs) and years lived with disability (YLDs) . For YLLTo estimate the DALYs of cancers attributable to the two selected risk factors, PAFs were estimated by combining the relative risk (RR) and rate of exposure to risk factors (Pe) using Levin’s formula for PAF .(1)PAF=RR indicated the relationship between each risk factor and health outcomes, cancer incidence, or mortality rates. PAFs represented the fraction of disease and injury in a population due to exposure to a risk factor  ,34. The To accurately estimate the incidence of cancer using the cohort data, a washout period of 2 years (2002–2003) was used to exclude all cancer patients diagnosed with the cancers of interest within this period. Subsequently, the enrollment date was set as an individual’s 2004 or 2005 health check-up date. Since the entire population of Korean adults aged ≥40 years can apply for the general health screening program at least once every 2 years for the entire population of Korean adults aged ≥40 years , the ranTo calculate the exposure rates for smoking, alcohol consumption, and combined smoking and alcohol consumption in men and women aged ≥40 years, frequency analyses were performed using the 2004 and 2005 NHIS-NSC databases. Individuals who responded, “I currently smoke” were categorized into the smoking exposure group, and individuals who indicated an alcohol consumption frequency of “>3–4 times a week” and alcohol volume consumption per event of more than “a bottle of soju” were categorized into the alcohol exposure group. Soju is the most popular Korean liquor drink that generally contains 17.5% alcohol per bottle (360 mL). The study aimed to match the operational definition of high-risk alcohol consumption used by Korea Health Statistics as closely as possible. In addition, individuals who met both the smoking and alcohol exposure definitions were categorized into a smoking and alcohol consumption (SA) group, indicating exposure to both risk factors. Finally, individuals who did not actively smoke cigarettes and did not consume alcohol were categorized into a nonsmoking and non-alcohol consumption (NSNA) group.To determine the relationship between exposure to risk factors and cancer incidence or death, RRs were calculated. Individuals who participated in the national health screening program in 2004 or 2005 and whose data were used for RR calculation were divided into risk factors-exposed and non-exposed groups. Individuals with a medical record of target cancer prior to their 2004 or 2005 medical examination were excluded from the analysis.To calculate the RR between risk factors and the incidence or mortality related to each cancer, the Cox proportional hazards model was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. The operational definition of smoking in the calculation of the HRs was applied differently from that used in estimating the exposure rate of smoking, as there is a lag-time of ≥20 years between exposure to smoking and disease incidence . CurrentThe start date of the follow-up period was based on each individual’s medical examination date in 2004 or 2005. Survival time for each participant in our study was defined as the length of time from the date of the medical examination to the date of the earliest occurrence of one the following: cancer diagnosis, cancer death, loss to follow-up, death, or 31 December 2015, which was the maximum traceable time in the NHIS-NSC database. If HR calculations were not possible owing to an insufficient number of individuals in one sex group, sex-adjusted values for the same disease were substituted.p-value of <0.05.When the estimated HR value was <1 for risk factors, an HR of 1 was used instead for PAF calculation. Previous studies ,19,20,21Factors confirmed to be associated with the incidence or mortality of each cancer type were considered as covariates in the analysis model, which included age, residential area, income level, frequency of physical activity, total cholesterol level, fasting blood sugar level, body mass index, blood pressure, family history of cancer, personal history of hypertension, and personal history of diabetes mellitus. In the calculation of HRs, the fit of the Cox proportional hazard model was determined by analyzing Schoenfeld residuals. Meanwhile, covariates that did not satisfy the proportional hazards assumption were excluded from the model. Final adjusted HRs are reported. All analyses were performed using SAS 9.4 , and statistical significance was set at 5%.xADALY was the DALYs attributable to risk factor x, dYLL was YLLs of cancer d, xddPAF was the fraction of YLL for cancer d due to risk factor x, dYLD was YLDs of cancer d, and xdiPAF was the fraction of YLD for cancer d due to risk factor x. The burden of cancer attributable to each risk factor was equal to the sum of the attributable burdens for each cancer type related to that risk factor.To estimate the DALYs for a specific cancer type attributable to exposure to each risk factor, we multiplied PAFs for incidence or mortality by YLLs or YLDs and summed attributable YLLs and YLDs according to sex, cause (specific cancer), and risk factor. The equation used to calculate the DALYs for cancers in Koreans attributable to smoking and alcohol consumption was as follows:Compared with the NSNA group, the SA group had an increased risk of mortality due to esophageal cancer ; liver cancer ; laryngeal cancer ; tracheal, bronchial, and lung cancers ; colon and rectal cancers ; and pancreatic cancer . Of these, the risk of mortality from esophageal cancer and liver cancer due to exposure to combined smoking and alcohol consumption was higher than that due to smoking and alcohol consumption when considered independently . DetaileOverall, the PAFs associated with risk factors were higher for cancer mortality than for cancer incidence. Among Korean men aged ≥40 years, combined smoking and alcohol consumption contributed most to cancer mortality for laryngeal cancer (69.2%), followed by esophageal cancer (34.0%) and cancer of other parts of the pharynx and oropharynx (27.7%). In women, combined smoking and alcohol consumption-attributed mortality rate was the highest for laryngeal cancer (4.6%), followed by for tracheal, bronchial, and lung cancers (4.4%) and esophageal cancer 1.9%; .In contrast, the burden of cancers attributable to smoking and alcohol consumption was relatively smaller in women than in men. In Korean women aged ≥40 years, the total DALYs for cancers related to combined smoking and alcohol consumption and those related to smoking and alcohol consumption considered separately were 2666 (1.1%), 6080 (2.5%), and 6599 (2.7%), respectively. Among the 12 evaluated cancer types, even those with the highest contribution to the burden of cancer did not reach 10.0%.To our knowledge, this is the first study to quantitatively estimate the burden of cancer attributable to smoking and alcohol consumption in Korean adults aged ≥40 years using DALYs, a summary measure of population health. This study considered the combination of smoking and alcohol consumption to estimate the combined effects of multiple risk factors. Combined smoking and alcohol were found to account for 9.5%  of cancer burden in men and 1.1% (2666 person-years) in women. In men, the burden of cancer attributable to smoking alone was 14.8%  and that due to alcohol consumption alone was 6.1% ; corresponding values in women were 2.5% (6080 person-years) and 2.7% (6599 person-years), respectively.We found that the burden of cancer attributable to combined smoking and alcohol consumption from the highest to the lowest number of DALYs for men was tracheal, bronchial, and lung cancers; liver cancer; stomach cancer; colorectal cancers; and pancreatic cancer. In women, the ranking differed slightly as follows: colorectal cancer; tracheal, bronchial, and lung cancers; stomach cancer; liver cancer; and pancreatic cancer. We compared these findings with the most recently published GBD results for 2019 [The risks of cancer incidence and death in individuals who were both active smokers and consumers of alcohol were investigated and compared separately with those of active smokers or alcohol consumers according to sex and specific cancer site. In men who both actively smoked and consumed alcohol, the risks of esophageal cancer; liver cancer; and tracheal, bronchial, and lung cancers were 4.4-, 1.6-, and 2.3-times higher, respectively, than those in non-smokers and non-consumers of alcohol. Furthermore, in men, the HRs of the combined risk factors for death from esophageal cancer and liver cancer were 6.1 and 2.2, respectively. These comparisons were not possible in women because no cancer with significant HR was identified in those who both smoked and consumed alcohol or in those who either smoked or consumed alcohol.Several studies have compared independent and combined effects of risk factors, focusing on modifiable lifestyle factors. In particular, several studies have estimated the effects of combined smoking and alcohol consumption, focusing on pharyngeal and esophageal cancers. Castellsagué et al.  comparedSeveral international studies have investigated health effects associated with combinations of various risk factors; however, such studies have not yet been undertaken in Korea, making comparisons with present findings challenging. In Korea, only the association between individual health risk factors and cancer risk has been investigated, wherein studies have evaluated specific age groups, diseases, and regions ,47,48. IHowever, unlike that in men, the impact of risk factors on cancer incidence or mortality rates in women could not be estimated using the research model in our study. Therefore, the PAFs were calculated by substituting the estimated HRs by adjusting for sex. Sex differences in the effects of risk factors on disease onset have been reported ,50,51. BIn this study, the burden of lung cancer in men was the highest among the cancers studied, and the proportion of diagnoses due to combined smoking and alcohol consumption was also high (16.8%). These findings indicate that 16.8% of the burden of lung cancer, a major disease that afflicts Korean men, could have been prevented if men aged ≥40 years had refrained from smoking cigarettes and consuming alcohol.PAFs indicate the proportion of disease risk that could have been prevented if exposure to a risk factor had been eliminated. PAFs are influenced by the prevalence and contribution of certain risk factors to disease development. Therefore, the use of PAFs in this study supports the translation of the present findings to policy decisions. This study examined cancer burden by sex. However, within the entire population, there are also differences in lifestyle in terms of age group, occupation, and residential area. In addition to the level of exposure to risk factors, the health effects of risk factors are likely to differ for each subgroup. In Korea, through the Integrated Health Promotion Program, local governments run projects that help promote healthy living and prevent chronic diseases; these programs are tailored to local resident characteristics and needs. Since 2013, this program has supported local government autonomy, reducing the impact of the state-led top-down approach. Accordingly, it is necessary to proactively develop and promote various projects to improve the health of residents according to local needs. Ultimately, an effective process for targeting population subgroups and health risk factors is needed to maximize the effectiveness of health care services and reduce health inequality. However, studies evaluating interventions in each target group, considering regional characteristics, have yet to be conducted. Although this study focused only on smoking and alcohol consumption and related cancers, the methodology applied in this study may be expanded upon and utilized further in other contexts. Further studies are required to estimate disease burden attributable to regional risk factor distributions, disease risks, and population structures. In addition, efforts to improve the limitations of previous health policies, which focused only on the intervention of a single risk factor, need to be further supported by empirical evidence. This study suggests that the combination of various health risk factors need to be accounted for in any policy development. In-depth studies should be conducted on more diverse diseases to develop specific and diverse intervention strategies for complex health risk factors. Consequently, more effective health care services should be established according to population characteristics.This study had some limitations. First, owing to limitations in the data sources, the operational definition of high-risk alcohol consumption suggested by Korea Health Statistics could not be accurately matched. Second, the NHIS-NSC data source for PAF estimation designates some categories, including breast cancer, as sensitive diseases that are subject to data masking. Future research may obtain higher quality evidence by calculating the HRs for all diseases related to the risk factors of interest using national health screening raw cohort data. Despite these limitations, our findings provide an empirical basis for measuring disease burden due to risk factors using PAFs and DALYs by analyzing data representative of an entire population. Comparing the magnitude of disease burden according to cancer type may provide meaningful data for health policy development and estimations of disease burden that can be reduced by alterations in health behaviors.Our results suggest that in Koreans aged ≥40 years, simultaneous exposure to smoking and alcohol consumption is associated with higher cancer incidence and death rates than those associated with either of these factors; these associations are further mediated by sex and specific cancer site. The attributable disease burden may be further associated with age and occupation; this evidence may help develop interventions applicable to each sub-group. The presented methodology may be used in future studies examining the disease burden and effectiveness of interventions in various groups and disease types.


To examine the relationship between dietary fat intake and breast cancer (BC) development.P values below 0.05 were regarded as statistically significant.This case-control study included 473 women with breast cancer  and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. 2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat , saturated fatty acid (SFA) , monounsaturated fatty acid (MUFA)  and PUFA intake  with BC risk in postmenopausal women. However, there was no association in premenopausal women.Participants’ age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/mTotal dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.The online version contains supplementary material available at 10.1186/s12944-021-01557-y. Breast cancer (BC) is the most prevalent cancer in women and the second foremost reason for cancer-related deaths in developed countries after lung cancer . It is pIn addition to age, genetic and reproductive factors, other determinants like overweight or obesity, lack of physical activity, using alcohol and smoking as modifiable risk factors have been linked to BC , 5. The Overall, a few studies have assessed the association between various types of fat intake and BC risk in the Middle-Eastern countries, as dietary intake and environmental issues are considerably different in this region  . TherefoThis was a case-control study performed from May 2014 to April 2016. Women aged 19–80 years (n = 486) with BC verified by pathological study entered the trial. All cases were recruited from patients referred to the Cancer Institute, situated at Imam Khomeini Complex in Tehran. Participants did not have any long-term dietary restrictions and history of any other cancers whom was new breast cancer cases. Controls (n = 516) were selected from healthy women who were relatives and friends of patients without cancer who were referred to Imam Khomeini Hospital Complex, Tehran, Iran. Controls were matched regarding the place of residence  and age (5-year groups). Cases and controls were selected based on convenience sampling. According to the study design, participants who had either no response to more than 70 items of the food frequency questionnaire (FFQ) or a reported total energy intake of more than 5500 or less than 800 kcal/d (n = 116) were excluded. Ultimately, 473 cases and 501 controls entered the final analysis. Written informed consent was obtained from all participants. The study protocol was approved by the Bioethics Committee of Tehran University of Medical Sciences, Tehran, Iran (Ethics code: 93-03-51-27113).Dietary intake assessment. The usual intake of 168 food items in the last year was assessed using a semi-quantitative FFQ by interviewing trained investigators. The reliability and validity of this FFQ were investigated by comparing data from two similar FFQ completed one year apart according to previous investigations [igations , 28. Theigations  to calcuigations . The daiAssessment of other variables. BMI was calculated as weight in kilograms divided by height in meters squared. Physical activity assessment was done through the Global Physical Activity Questionnaire (GPAQ) validated for adults [r adults . This qur adults . The dur2 test was used where appropriate. Also, multivariable logistic regression was performed to evaluate any correlation between dietary fat and fatty acid with the development of BC. In the first model, adjustments were made for energy intake and age. In the multivariable model, further adjustments were considered for cigarette smoking, physical activity, alcohol consumption, BC family history, marital status, educational level, parity, and BMI. The first quartile of fat intake was considered as the reference group. All the analyses were performed using STATA version 14 (State Corp.). P values < 0.05 were considered as statistically significant.Data were analyzed according to menopausal status or in all participants as a whole. Total energy intake was adjusted as a confounding factor using the residual method . ThereafThe study included 473 cases  and 501 controls . Participants’ characteristics are depicted in Table νs. 43.9 years), had a family history of BC more frequently (46 νs. 7 %), and had lower BMI (28.1 νs. 28.8 kg/m2) compared with the control subjects. Also, they had lower physical activity (22.7 νs. 29.4 MET h/wk). Besides, they were less likely to use oral contraceptives (53 vs. 61.2 %) postmenopausal hormones (0.42 vs. 2 %) or drink alcohol (2.5 vs. 5.9 %) than controls.Patients with BC were older (45.8 P = 0.02), SFA , and PUFAs , and a lower intake of oleic acid  compared with the controls . The stratification by menopausal status showed that premenopausal women with cancer had a significantly higher intake of energy  and SFA  than controls. Also, SFA  intake was higher in postmenopausal women with cancer compared to controls.As shown in Table The estimated OR and 95 % CIs for BC according to quartiles of fat intake are shown in Table In a subgroup analysis based on menopausal status, a positive association was found between animal fat , SFA , MUFA  and PUFA intake , with the risk of BC in postmenopausal women. Nonetheless, no association was found in premenopausal women.The dietary total fat intake was positively associated with BC risk in all participants who entered the current investigation. Also, higher PUFA intake was related to an increased possibility of BC. However, the associations were significant only among postmenopausal women after the stratification of analyses based on menopausal status. These results indicate that a higher intake of animal fat, SFA, MUFA, and PUFA was associated with a higher risk of BC in postmenopausal women. Moreover, a direct association was observed between total fat and PUFA intake and BC risk in all participants as a whole. On the contrary, the Nurses’ Health Study found no association between any fat subtypes and BC . Also, aA significant positive association was also reported between dietary fat subtypes and the risk of BC in postmenopausal women, but there was no association in premenopausal women. In contrast to the current findings, two studies , 36 repoIn the present study, SFA and MUFA intake also increased BC risk in postmenopausal women. These findings regarding SFA were similar to some investigations that showed an increase in BC risk in postmenopausal women , 40. HowMoreover, in this study, there was a positive association between a higher intake of MUFA and the risk of BC in postmenopausal women. In line with the present study, in two observational studies, BC risk was directly correlated with MUFA intake , 47. On Stearoyl-CoA desaturase-1 (SCD1) enzyme is an important controller of fatty acid configuration in mammalian cells and plays a role in stearic acid to oleic acid conversion. In tumoral cells, SCD1 plays as a key regulator for lipogenesis able to enhance the activity of several oncogenic signaling pathways like Akt and PKC, which are activated by oleate . TherefoIn the present investigation, higher PUFA intake was related to BC risk in women with menopause. Limited studies have examined the link between PUFA intake and BC risk stratified by menopausal status. However, in the Malmo Diet and Cancer study, Wirfalt. et al. reported a positive association between PUFA intake and BC development in postmenopausal women . Also, oDifferent associations found in pre- and post-menopausal women might be explained by differences in body fat percentage. As in this study, the hypothesis of associations between body fat and BC could not be approved in premenopausal women. Likewise, Zhao et al. in a study in premenopausal women reported that reduced expression of RPS6KB1, ESR1, and GATA3 in breast adipose tissue plays a role to decrease the risk of breast cancer . Other rThis investigation had some strengths. A quite big sample size, using standard questionnaires, performing a categorized analysis by menopausal status, and considering several confounding factors were some strengths. Prior studies found animal fat adversely affects BC risk in only premenopausal women; however, the current study found this association in postmenopausal women.This study had some limitations. First, this was a case-control study, and the selection or recall bias could have affected the results. Second, the possibility of under- and over-reporting of either energy intake or special food groups and recall bias exists when using the semi-quantitative FFQ. Third, although FFQs are often used to categorize participants’ intakes rather than meticulous measurement of nutrient intake, a degree of gross misclassification is inevitable. Fourth, BC was not ruled out in controls. Fifth, the current study could not assess the hormonal receptors status and no information was available regarding breast cancer stage or grade.There was a direct association between total dietary fat and subtypes of fat intake with the risk of BC development particularly in women with menopause. This observational study provides support for the importance of dietary fat intake in increasing the risk of breast cancer. Therefore, the amount of dietary total fat as well as fatty acids should be recommended with caution to reduce the risk of BC. More intervention studies considering the effect of dietary fats on cell growth considering different subgroups of estrogen receptors are required.Additional file 1


Breast cancer became the most common cancer globally in 2021, according to the World Health Organization. The aim of the study was to evaluate risk factors for breast cancer, such as early alcohol use initiation, obesity, breastfeeding, and place of residence. The effect of alcohol consumption by girls has been assessed in only a few studies and is not fully understood. In this study, it has been found to be associated with a higher risk of breast cancer. Our study also shed light on the incidence disparity—women were more at risk in the countryside than in the city. The results of this study should be included in the preparation of breast cancer prevention programs and also aimed at women in adolescence and early adulthood because exposures during childhood and adolescence can affect a woman’s long-term risk of breast cancer. Every effort should also be made to ensure that access to knowledge is open to all, regardless of where they live, giving all women equal opportunities.The aim of this study was to determine the risk factors for breast cancer in the Polish population. In total, 201 Polish women newly diagnosed with breast cancer and 201 one-to-one age-matched healthy controls participated in this case-control study. Data on sociodemographic characteristics, reproductive and menstrual history, medical history, lifestyle factors, and anthropometric measurements were collected by the interviewers. Odds ratios and 95% confidence intervals were obtained using multivariate unconditional logistic regression models controlling for potential confounders. Significant relationships were observed between BMI, alcohol use initiation, breastfeeding, education, and place of residence. Obese women had a higher risk of breast cancer than women with a BMI < 30 . Early alcohol use initiation (≤15 years) was associated with an almost two-fold higher risk of breast cancer . Breastfeeding for less than 3 months , receiving a basic and vocational education , and living in a rural area  increased the risk of breast cancer. Prevention activities for breast cancer are already needed in adolescents and young women. A much greater emphasis should also be placed on breast cancer prevention campaigns in rural areas in Poland. With more than 1.5 million new cases diagnosed each year, breast cancer is the most common cancer in the world and the leading cause of cancer-related deaths among women. This number continues to grow, especially in highly developed countries ,3,4. TheBecause most of the risk factors for breast cancer are unmodifiable, the emphasis should be placed on those that can be modified, such as early alcohol consumption. Although it may seem that this factor has been studied extensively, its impact on women’s health requires more detailed analyses. While alcohol consumption among adult women has been consistently associated with an increased risk of breast cancer ,8, littlAnother risk factor discussed in the current literature is breastfeeding, which has a protective effect on the mother later in life ; nonetheThis study also discussed other important factors that increase the risk of breast cancer, especially obesity in the post-menopausal period ,18,19,20It is estimated that more than one-fourth of breast cancer cases could be prevented by maintaining a healthy body weight, abstaining from alcohol, engaging in physical activity, and breastfeeding, thereby reducing the exposure of women to exogenous oestrogens .Examining the risk factors for breast cancer in Polish women may expand the current knowledge on this important topic and act as one of the building blocks of prevention. To our knowledge, alcohol use initiation in the context of breast cancer has not been analysed in the Polish population thus far. Therefore, the aim of our study was to assess the relationship between breast cancer risk and early alcohol consumption, place of residence (city/village), breastfeeding, and obesity in a sample of Polish women.n = 201) who were admitted to the Oncological Surgery Clinic of the Medical University of Gdansk between January 2015 and June 2017, with diagnoses of breast cancer made no more than three months prior to the study. Patients diagnosed more than three months in advance of the study were not included, with the aim of controlling for changes in dietary habits or other behaviours. Additional inclusion criteria for cases were as follows: age between 50 and 69 years, provided consent to participate, and the ability to understand and answer the questionnaire. Women previously diagnosed with breast cancer and women who were unable to answer the questionnaire due to health, language, or educational barriers were excluded. During the same period, breast cancer (BCA) patients received an additional questionnaire to give to healthy women of the same age in the same place of residence who were of a similar economic status. A total of 201 female controls without any clinical symptoms or other signs or suspicion of any type of cancer in their medical history were selected. The questionnaire included a question about the date and result of the last mammogram; only women with normal mammography outcomes were eligible to be enrolled as controls. The participants in the control group were matched in terms of age (≥50) with the cancer patients and selected among residents of the same areas as the cases. Interviewers visited the participants who were selected as controls or asked the participants to complete the questionnaire and return it by mail. If a suitable control could not be selected among women in the BCA community, the researchers attempted to find an appropriate control using their own social network (20% of cases).This study was designed as a case-control study with face-to-face interviews. The participants were selected from among Polish women diagnosed with incident, primary, and histologically-confirmed breast cancer (A sample size of 402 women (201 cases and 201 controls) was estimated to be necessary to observe a significant association between early alcohol use initiation and the risk of breast cancer. The sample size calculation was performed using the standard formula , taking The self-created questionnaire consisted of questions regarding age, education level, and place of residence (city or village). The period of alcohol use initiation was divided into three groups: under 15 years of age, 16–18 years of age, and over 18 years of age. The participants were also asked about alcohol consumption in the year prior to the interview. The type of alcohol was converted into amounts: consuming more than 12 g/day was considered risky. Data on height and body weight were used to calculate current BMI according to the following formula: body mass (kg) divided by height (m) squared. Participants in the study were asked about their physical activity: daily physical activity  was classified as high, physical activity 2–3 times per week was classified as moderate, and physical activity once a month or less frequently was classified as lack of physical activity. Smoking habits  were also recorded. Family history of breast cancer, gynaecological history ), age at first pregnancy, miscarriage/abortion, number of children, and length of breastfeeding were recorded during the interview. Questions regarding mononucleosis history and exposure to ionising radiation during early childhood were also included in the questionnaire.Data from the questionnaire were input into Statistica 13. The Student’s t-test was used for independent samples to evaluate the mean differences of normally distributed variables  between cases and controls; in the case of skewed variables, the tested hypothesis was evaluated using the non-parametric Mann–Whitney U test. The univariate analysis was used to evaluate the OR and 95% CI and to estimate the relationship between individual risk factors and breast cancer. Multivariate logistic regression was applied to evaluate the association between breast cancer and education, alcohol initiation, breastfeeding, place of residence, and BMI. The analysis was adjusted for potential confounding factors, such as age, smoking (ever), physical activity , family history of breast cancer, age at menarche, age at first pregnancy, radiation in childhood, childhood illnesses, inter alia mononucleosis, and use of HRT. The variables were selected using a backward stepwise regression. Based on the ultimate model, the significance level was set at 0.05. The results of the logistic regression analysis were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).The basic characteristics of women who participated in the study are presented in p = 0.05), less frequently reported breastfeeding , and were more often obese as compared to healthy women . Moreover, cases frequently only had primary education  and lived in rural areas . There were no statistically significant differences regarding smoking, drinking over 12 g alcohol per day (in the 1 year preceding the interview), physical activity, and menopausal status between the groups. Women in both groups were also characterised by similar family histories . The higher use of HRT among cases as compared to controls  is also worth noting because it could turn out to be significant in a larger population. The univariate analysis (Cases and controls were of similar age (mean age: 58 ± 6 years old). Cases started consuming alcohol earlier in life as compared to controls  and an increased risk of breast cancer. These findings are noteworthy because the most well-known risk factors for breast cancer seem to play a role in early life during breast development and puberty . Ying LiThe influence of alcohol on the risk of breast cancer is most often explained by the fact that alcohol affects the levels of circulating sex hormones, where high levels of oestrogen in the blood are associated with an elevated risk of breast cancer. Alcohol increases the concentration of oestrogen in the blood, rendering the oestrogen concentration particularly high in the middle of the menstrual cycle (27–38% higher than in abstainers) when the oestrogen levels are already high by nature; hence the conclusion that alcohol can contribute to the processes of neoplasia more strongly in adolescence than in adulthood . UnfortuIn congruence with previous epidemiological studies, our study showed that the lack of or only a short period of breastfeeding, obesity, and residing in a rural area are associated with an increased risk of breast cancer. A meta-analysis of cohort and case-control studies has shown that breastfeeding women, regardless of ethnic and cultural conditions, have a lower risk of breast cancer compared to women who never breastfed . Other sOur study also confirms the importance of obesity as a risk factor for breast cancer. The WCRF recognised obesity in adulthood as a factor increasing the risk of post-menopausal breast cancer . MoreoveThe results of this study also indicate that residents of rural areas have a significantly higher risk of breast cancer than residents of urban areas. A similar trend has been observed in England . In PolaAs in all case-control studies, the major limitation of this study was recall bias. However, an effort was made to minimise this limitation by choosing newly diagnosed consecutive patients and recruiting the necessary participants in a short period of time. Another limitation is that the study was performed only among Caucasian women who have a high rate of breast cancer. Therefore, the results of the study cannot be generalised to the entire population. Furthermore, the study did not include a question about the use of hormonal contraception, which may be an additional limitation. Furthermore, bodyweight was not queried prior to diagnosis, which may be an additional limitation of the study. However, it was assumed that the study would include patients with a diagnosis not older than 3 months, which should minimise such error.In conclusion, we found that early alcohol use initiation, breastfeeding for less than 3 months, obesity, living in a rural area, and a lower education level were associated with an increased risk of breast cancer in our study sample. Furthermore, the results of our study indicate the need to create breast cancer prevention programs aimed at girls and young women to ensure awareness regarding alcohol consumption at an early age, before the first pregnancy, as a risk factor for breast cancer.