Results did not vary by chronotype (Pintx=0.74). Co-twin analyses, though with limited power, suggested that night work may be associated with breast cancer risk independent of early environmental and genetic factors. These results confirm a previously described association between night shift work and breast cancer risk. Genetic influences only partially explain these associations.Breast cancer is highly prevalent yet a more complete understanding of the interplay between genes and probable environmental risk factors, such as night work, remains lagging. Using a discordant twin pair design, we examined the association between night shift work and breast cancer risk, controlling for familial confounding. Shift work pattern was prospectively assessed by mailed questionnaires among 5,781 female twins from the Older Finnish Twin Cohort. Over the study period (1990–2018), 407 incident breast cancer cases were recorded using the Finnish Cancer Registry. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential confounders. Within-pair co-twin analyses were employed in 57 pairs to account for potential familial confounding. Compared to women who worked days only, women with shift work that included night shifts had a 1.58-fold higher risk of breast cancer , whereas 2-shift workers not including night shifts, did not . Women with longer sleep (average sleep duration > 8 h/night) appeared at greatest risk of breast cancer if they worked night shifts (HR = 2.91; 95%CI, 1.55–5.46; P BRCA1 and BRCA2, with a 70% lifetime risk of breast cancer for the women who carry mutations in these genes [Breast cancer remains the number one cancer among women worldwide, affecting one out of 8 women over her lifetime . Genes hse genes –5. Howevse genes , 7. Givese genes , studyinNight shift work constitutes one of the most prevalent forms of circadian rhythm and sleep disruption , 9, withPrior evidence suggests that common variations in circadian genes may increase the susceptibility to breast cancer among night shift workers –19. ThusThe exclusively female base population for the current analyses was nested within the Older Finnish Twin Cohort, – a long-running prospective cohort study, which started in 1975 by mailing a baseline questionnaire to all Finnish same-sex twin pairs that were born before 1958 and where both co-twins were alive in 1975 (89% response rate) . BrieflyOur primary exposure of interest was a woman’s self-reported (1990) shift work pattern based on current or latest work type. Rotating-shift work referred to work that rotated through morning, evening, or night shifts in either a two-shift or three-shift pattern. Shift work information was queried by assessing the respondent’s current or latest work type. The question “The present work or the work you last did (mainly) is regular day work, regular night work, two-shift work without a night shift, two-shift work with a night shift, three-shift work, or never worked”. We classified these data into 3 categories . Further, night work history was also assessed in 1975 and 1981 but did not distinguish between 2-shift work with versus without night work; as well as in 2011, using the same question as posed in 1990 but only among the subset of women born in 1945–1957 who were presumably still in the workforce in 2011. We used these additional night work assessments for sensitivity analyses (1) creating a stricter definition of the reference group “never night work” ; and (2) using the 2011 night work assessment as baseline.In addition to night/shift work exposure, information on sleep duration and quality was queried in 1990, while chronotype was assessed in 1981. Specifically, usual sleep duration over a 24-hour period, and hours of sleep needed during the night to be alert the next day  was asseData on breast cancer incidence (ICD-10 code 174) were obtained through record linkage  to the Finnish Cancer Registry, where 100% of registered cases are histologically verified. The Finnish Cancer Registry is a nationwide database with information on all cancers diagnosed in Finland since 1953 . Cancer 2) and BMI at age 20 (queried on the 1990 questionnaire), physical activity , use of oral contraceptives , alcohol consumption , educational status , socioeconomic status i.e. social class , and zygosity . Information on age at first child-birth and number of biological children was available for women born between 1950 and 1957 ; in sensitivity analyses restricting to these women and excluding childless women, we explored confounding by parity. Log–log plots of survival curves of the shift work exposure categories were used to verify that the proportional hazards assumption was not violated. We created indicators for missing values of categorical variables.After all exclusions, 5,781 female twin individuals who had replied to the 1990 survey that included questions on night shift work and were free of breast cancer at that time formed the base population for these analyses. Women contributed person-time from the return of the 1990 questionnaire and were censored at first report of any cancer, the date of diagnosis of breast cancer, date of death, or the end of follow-up , whichever came first. During this follow-up period (1990–2018), 5,781 women contributed 149,756 person-years at risk for breast cancer. Cox proportional hazard models (with age (in years) as the underlying time metameter) were used to calculate age-adjusted hazard ratios and 95% confidence intervals in each night work exposure category compared with the reference category. Due to the dependent nature of this sample of twin pairs, standard errors and CIs were adjusted for possible within-pair correlations using robust variance estimators. In multivariable analyses, we further adjusted for risk factors for breast cancer, including smoking status , current (1990) body mass index .In analyses stratified by chronotype, we found that the positive association between 3-shift night work and breast cancer risk was similar, regardless of chronotype or sleep duration  of all breast cancers were ductal carcinomas, with 71 lobular and the remaining tumors of varying histology. Due to small case numbers, we were not able to explore differences in risks by histology. However, restricting to the ductal breast cancer cases only did not alter our estimates substantially (data not shown).Coincidentally i.e., without prior hypothesis but as part of our verification of the proportionality assumption , we observed considerable differences in the risk of breast cancer among night workers depending on the women’s birth decade Fig. . SpecifiIn a co-twin analysis to assess the association between night shift work exposures and breast cancer risk within twin pairs discordant for breast cancer, we observed 25 pairs where the breast cancer case worked night shift (n = 25) and co-twin sister did not ; and 17 pairs where the healthy sister worked night shifts and the breast cancer case did not (14 day workers and three 2-shift workers). For all pairs where the numbers were large enough to allow analysis, the conditional logistic regression for matched pair data (which ignores time to event and censoring) estimated a 41% increased but statistically non-significant risk . The stratified Cox HR was slightly smaller . After adjustment for all covariates, the estimates did not change .The pairwise estimates in these analyses were very similar to those from the analyses on individuals, suggesting a higher risk of breast cancer among night workers even after accounting for potential familial confounding (genetics and shared family environment). There were also three twin pairs concordant for night work despite discordance for breast cancer .To our knowledge, no prior study on the impact of night work on breast cancer risk among twins exists. Consistent with previous reports among singletons, we found an elevated risk of breast cancer among women working night shifts in a large, prospective, population-based cohort study of Finnish female twins. Specifically, women who worked two or three shifts involving night work, or night shifts only, had a significantly higher risk of breast cancer than women working days only, either as day work or two-shift work. While there was no interaction between night work and sleep or chronotype, compared to day workers, we observed a significantly increased risk of breast cancer among women with longer sleep duration, i.e., more than 8 h of sleep on average, but not among the women with 8 or fewer hours of average sleep. Neither sleep duration, nor sleep quality or chronotype were individually associated with breast cancer risk in this cohort. Taken together, our data are confirmatory of earlier reports of an increased breast cancer risk among night workers, and they provide unique suggestive evidence for additional effects of night work beyond an individual’s genetic risks.Night work and its association with cancer risk has been extensively studied in prior analyses and was evaluated by large consortia in conjunction with the existing evidence from animal studies and mechanistic studies , 29, 30.Mechanistically, multiple pathways have now been demonstrated in support of a night work – cancer association , most ofA second finding of interest in our analyses pertains to the results on discordant twin pairs. Though underpowered, these suggest an effect of night work above and beyond familial and genetic risks. That the association between night work and breast cancer risk was slightly attenuated in the co-twin analyses discordant on night work and breast cancer outcome, compared to the main effects  may suggest that the main effects could at least partially have been explained by an unaccounted for shared genetic or environmental factor, and that the possibility of a factor influencing both night work and breast cancer should be further explored. While no evidence exists to support the heritability of the propensity to work night shifts, an earlier report from the powerful Nordic Twin Study of Cancer (NorTwinCan) estimated the heritability of liability to breast cancer to be about 20 to 28% . AlternaInterestingly, in our study, the night workers with longer sleep duration appeared to be at highest risk of breast cancer though case numbers were small in this stratum. Examinations of the interaction between night shift work and sleep duration and their association with cancer risk have only recently been emerging. They highlight the phenomenon of shift work disorder, i.e. a night shift worker who develops a set of symptoms lasting for at least 3 months in response to their night schedules. Symptoms foremost include sleep problems in the form of insomnia; but also excessive sleepiness and to some extent sleep duration . SeveralContrary to a previous studies examining the association between chronotype, work type, and prostate (42) or breast cancer risk , we did Lastly, our observation of a birth cohort effect in our results deserves note. We are not aware of any earlier reports that have examined whether their results of an association between night work and cancer risk differed by birth cohort of the study participants. However, the inherently longer follow-up among the older birth cohorts will likely have increased the post-retirement time for these women; and we have previously described that night-work associated breast cancer risk may wane once a woman stops working night shifts i.e. in retirement . AnotherOur study has several limitations of note. We were not able to adjust for a few important breast cancer risk factors including menopausal status, postmenopausal hormone use, and age at first birth. However, information on these variables was available in a smaller subset of the women, which allowed us to conduct sensitivity analyses; reassuringly, results did not change by much in these analyses. Nonetheless, as in any observational study, the potential for residual and uncontrolled confounding by e.g., other occupational factors, remains. Further, important differences in the associations by ethnicity/culture have previously been noted ; given tSome strengths of our study also deserve mention. First, the follow-up time of up to 28 years, from 1990 to 2018, is long enough for a chronic disease like breast cancer to occur. Second, as twins do not differ from singletons in e.g., cancer incidence  and sleeIn conclusion, in this prospective, population-based cohort study of Finnish female twins, we found a significant association between night work and breast cancer risk, with some suggestively stronger effects in the subgroup of women with longer sleep duration requiring confirmation. Results from discordant twin pair analyses addressing the shared genetic and environmental risk factors for breast cancer suggest that night work may have carcinogenic effects above and beyond familial risks.


Background: Breast cancer is a leading cause of morbidity and mortality among women worldwide and in Thailand. Objective: To explore perceptions of breast cancer and screening prevention programmes among a group of at-risk women in a multicultural setting in southern Thailand. Methods: Semi-structured in-depth interviews were used for data collection with 30 at-risk group women. Women from Muslim and Buddhist backgrounds were purposively included in this study. The thematic analysis method was used to analyse the data. Results: Four themes were identified from our data: perceptions of breast cancer, being diagnosed with breast cancer and anxiety, stigma: effects of breast cancer, and breast self-screening and prevention of breast cancer. The participants had some knowledge about the risk factors for breast cancer. However, participants perceived that breast cancer could occur to individual women at any time and that it was not possible to entirely prevent the disease, even when following a breast self-examination programme. However, most participants perceived that whether one would be afflicted by breast cancer depended also on Allah and their own karma. All participants were encouraged to attend breast self-screening training by healthcare providers of local health centres, but they had no confidence to perform self-screening soon after finishing the training programme. This became the reason for a lack of regular self-screening with responsibility left to health practitioners. Although participants were aware that breast self-screening should be their routine practice, there were multiple barriers to this, including accurate knowledge about breast cancer, belief, self-awareness, screening skills and healthcare facilities. Breast self-screening was recognised as an important means of early detection. However, most women did not perform this regularly, which could increase their risk of developing breast cancer. Conclusions: Public health providers need to be more concerned about the perceptions, beliefs and practices regarding breast cancer and develop prevention practices that work better for women living in more diverse cultural locations so that they may be able to follow preventive practices and reduce their vulnerability to breast cancer. Cancer today causes higher morbidity and mortality rates worldwide compared with previous decades and this is likely to continue in the future ,2,3. CanIn Thailand, according to the National Cancer Institute, breast cancer incidence was reported to be about 40 per cent, and was the top disease diagnosed among Thai women. Although the rate of breast cancer was relatively high among 45–50-year-old women, there was also a high incidence of breast cancer among younger women. In southern Thailand (where our study was conducted), the Thai National Cancer Institute reported that these were about 26 per cent of the total breast cancer cases in 2019 .Breast cancer is caused by various factors, including postmenopausal age, late menopause, physical inactivity, undertaking hormone treatment, including estrogen and progestin, and even the use of alcohol ,5. FamilTo prevent the advance of illness and to reduce either morbidity or mortality rates, breast cancer screening plays a crucial role in ensuring early detection ,10,11. EMost women may have a good understanding that breast screening can prevent the severity of breast cancer. However, many still lack knowledge about correct screening skills and do not receive regular screening and care by healthcare providers, whilst some may not make it a priority in their daily lives. This is partly because of the influence of socio-cultural factors . In someIn Thailand, the Ministry of Public Health has promoted breast cancer screening vigorously since 2015 and continues to emphasise it as the main policy for reducing mortality rates. Comprehensive strategies have been combined in practice focusing on proactive breast cancer screening programmes by public health workers and educating at-risk groups to follow self-breast examination practices that will lead to early detection. However, the incidence rate of breast cancer in Thailand is still showing an increasing trend, as noted above .The study on which this paper is based examined the perception of breast cancer and prevention practices among women living in a multicultural community in southern Thailand. It was undertaken because little is known about this issue in this part of Thailand. This paper discusses perceptions of breast cancer and screening prevention experiences among a group of at-risk women in a particular setting. Thus, the findings from our study could be beneficial in terms of tailoring education in a culturally sensitive way to promote more practical interventions for at-risk groups of women living in rural environments, thereby promoting the uptake of breast cancer screening and helping women to avoid breast cancer.The health beliefs model was adopted for this study because the model can help to predict people’s behaviour based on whether they desire to pursue health promotion activities . This moOur paper uses these six dimensions to examine the perception of breast cancer and prevention practice on the part of a group of at-risk women in southern Thailand. It seeks to understand how these women perceived their susceptibility to breast cancer, the severity of the disease, the benefits they gained, the barriers they faced, and their self-efficacy beliefs regarding maintaining healthy breasts . An indiThis study adopted a descriptive qualitative design to gain a deep understanding of perceptions and screening prevention practices for breast cancer among risk group women in a multicultural community in southern Thailand. Semi-structured in-depth interviews were used to collect data . In-deptThis study obtained ethical approval from the Thaksin University Ethics Committee Thailand (COA No. TSU 2021-013 REC. No. 0252).Thirty women who met the criteria of the study were purposively invited to share their perceptions and beliefs about breast cancer and screening. Purposive sampling involves selecting potential participants who meet the criteria of the study . The incMore than one-third of the participants in this study were aged between 40 and 49 (40.00%) or had obtained a primary school degree (33.33%). More than two-thirds were Muslim (70.00%). The majority were married (83.33%). Agriculture was the main occupation among these women (66.67%). Two-thirds had no family history of any kind of cancer (60.00%). The majority had no history of breast problems (86.67%) The most usual method used for screening was breast self-examination. More than two-thirds of participants still experienced normal menstruation (73.33%). For those whose menstruation had stopped, the age when it stopped was most often over 50 (61.54%). The characteristics of the study participants are shown in We started carrying out data collection after obtaining ethics clearance from the university ethics committee. Before the interview, we made an appointment via village health volunteers who were responsible for participants’ healthcare in the study areas a day before confirming the appointed time and place for conversation. Most participants preferred to have the face-to-face conversation at the community centres located in the central part of the village where they felt more relaxed. Written informed consent was obtained before the interview started. The first author, who is a native speaker living in the southern region, asked several open-ended questions to each participant. These included: (1) how do you perceive breast cancer? (2) what would be the chance for women to develop breast cancer in a lifetime? (3) what would you do if you were diagnosed with breast cancer? and (4) can breast cancer be prevented? How? Notes were taken during the conversation to remind the interviewer to probe further.All interviews were conducted by the first author. She used the local language  for conversation to allow women to be more comfortable and able to articulate their perceptions and experiences related to the study objectives with more ease. Each interview lasted between one and one and a half hours and was recorded using a digital voice recorder. Interviews were continued until little new data emerged, indicating that saturation had occurred . A smallAll interviews were transcribed in the Thai language to maintain the original meaning. A thematic analysis method was used for data analysis . Open coIn addition, the rigor of the study was ensured by using the member checking method. As soon as each interview was transcribed, the first author checked the transcripts with study participants for accuracy prior to analysis of the data. After the coding and themes were completed, these were used as a basis for discussion with co-researchers. All translated verbatim quotes used in the paper were cross-checked with the second author who is a bi-cultural researcher and proficient in both Thai and English. These strategies helped to ensure the credibility of the data.Four themes were constructed from our data: perceptions of breast cancer, being diagnosed with breast cancer and anxiety, stigma: effects of breast cancer, and breast self-screening and prevention of breast cancer.pai heab or pai ngeab (a silent killer) as it did not show any obvious sign in advance, unlike other diseases. However, most would know when it had destroyed cells and mammary glands, which would be too late for them to prevent breast cancer. Kan, a Buddhist woman, mentioned:All participants in this study perceived breast cancer as a very serious illness. If a person got the disease, she would never be cured. She would live with many sufferings in life and die soon after being diagnosed, although there was advanced medical technology and the availability of modern medicine for treatment. Most women stated that cancer intruded on a patients’ organs and lymph nodes, leading to abscesses and infection of affected organs. They remarked that the lymph node was a susceptible part for the development of breast cancer and the lymph node was the food supply of cancer. It also quickly expanded to other organs to increase the severity of the disease. Breast cancer was perceived by participants as It is a very scary disease for all women who have this disease. It does not have any warning signs. We know when it comes to the third or fourth stage. There are no warning signs like coughing, so we ignore any abnormal signs. It means we just have to have our breasts cut out. Even though the breast was removed, it cannot be healed. We will die only.Both Buddhist and Muslim women stated that breast cancer was caused by various factors: genetics, environment, food consumption and individual behaviour. Many Buddhist participants stated that genetics was the main cause of breast cancer. If women had a breast cancer history in the family, they would have a higher chance of developing this disease compared to others who had no family history. The environmental conditions where they lived were recognised as contributing factors to breast cancer. From the perspective of many Muslim participants, nowadays people faced many kinds of pollution and chemical substances around them because they were living in the modern world. For example, there were many cars on the road, factory industry, chemicals used in agricultural areas, and in construction sites, which increased the risk of vulnerability to disease and illness. The food consumption behaviour of the individuals was the main contributing factor recognised by these participants. They pointed out that modern society encouraged people and young generations to consume grilled food, processed food, oily meal, and inorganic vegetables and meat. People no longer followed traditional ways of living, which relied very much on natural resources for living to promote good health. Kanee, a Muslim woman, said:If having genetic breast cancer, our generation and the next would have a high chance of getting this disease. The environment around us affects our lives. We get pollution from cars on the road. There are lots of fast food and chemical ingredients, you see. In the past, we didn’t have things like this. There were not many cars and we didn’t inhale pollution and gas like today.Some Muslim women articulated that breast cancer would occur among women who breastfeed. They explained that the breast had very soft tissue consisting of blood and lymph, so it was very susceptible to bruises, abscesses and infections. During breastfeeding, the breast would be bumped, and it would get bruised easily from touching and sucking. Later the tissue and cell around the breast could become decomposed and turn into cancer. They suggested that having discharge and purulence coming out from the nipple was an obvious symptom of breast cancer and these signs signified the development of breast cancer in the long run. More than one-third of Buddhist women participants reported that women who breastfed could get pain around the breast. The feeling of pain meant that the pathogen was intruding into blood and lymph systems. It would damage cells and tissue and could lead to breast cancer one day. Kanya, a Buddhist woman said:We have never known until we see blood and purulence come out from the nipples…then we can realise that we are the victim of breast cancer It is a very scary and serious condition for women, you see. No one wants this.tuk (difficulty) and suk (happiness) in life. Life was unpredictable. Individuals might not be affected by cancer, but they might have an accident or chronic illness. So, it was important for them to have awareness of their own breast health. Both Buddhist and Muslim women believed that disease, illness, or unhealthy conditions could occur to anyone at any time. It was difficult to know what disease would come to one and when it would disrupt the body. A Buddhist woman, Kayanee, said: “Life is uncertain, we never know and we have to tum jai (accept it). We could die by an ageing process, not because of any diseases. It is much better like this and it is okay to think like this”.All women hoped that they would not experience breast cancer, although they understood that, by the nature of living, that one would have a mix of Allah has given us life and he would control our health, life, and future…if he gave you breast cancer, you will get it one day. Believe me, we cannot avoid it”. Kama remarked:Many Muslim women believed that whether one would have breast cancer or not depended on Allah or Muhammad. They believed that illness was one of the means that Allah used to test human patience for his people. However, if one always acted with good deeds, and even if a woman was diagnosed with breast cancer, she would get a less serious condition and have a better chance of recovery. This is the nature of the human life cycle. Ka pee pointed out: “…Sometimes Allah just wants to test us to whether we have tolerance or are strong enough to live. Getting disease is somewhat the way to encourage people to develop the skill of dealing with suffering when facing life-threatening things. If some persons can accept [breast cancer diagnosis], if one can live with it, she is seen as strong woman or a patient who can lead a daily life. We have to accept what happened to our lives.kam in Thai. Due to her bad actions in the past, and if she had this disease in her previous life, a woman would not be able to avoid getting this disease again in this life and even the next life. Aree expressed her belief:For Thai Buddhist women, breast cancer was caused by one’s karma, referred to as …as a Buddhist person, I believed that if we have to face breast cancer in life, it is because I was afflicted by this disease in the past life…it might follow me to the next life thought because of good deeds (kam dee) and bad deeds (kam choa).…if one is diagnosed with breast cancer, her life becomes miserable. But we have to live with hope -try to live like others…”.Women perceived that breast cancer created suffering and uncertainty in life. Their lifestyles, in particular, would completely change. Many agreed that, if they were afflicted by breast cancer, their lives would be controlled by medicine and healthcare providers until the last minute of life. However, some stated that they had to continue their lives without being worried too much because the illness was a part of being a human being. They should understand and lead a normal life like others who did not have breast cancer. Mama expressed: “If being diagnosed with breast cancer, it is difficult to dress beautifully like others. The breasts will not be in a balanced shape. We have to think about how to fix the problem and it is a stressful thing. There are more burdens in life and we would have worries later on”.Stigma was an important effect of breast cancer raised by most women in the study. As the breast is perceived to be a symbolic part of being a woman, if one was diagnosed with breast cancer, it might be necessary that their breasts be removed, and this would affect their femininity. Many women imagined their future appearance and beauty as a result of a mastectomy operation. They pointed out that a person with breast cancer would undergo treatment and mastectomy and it was a common treatment they had seen. One would need to seek ways to restore breast shape and keep a good appearance as a woman which could create stress among them. Samami, a Buddhist participant, shared her thoughts: “Losing breast, even one side, how can we breastfeed children? It will be a shame if cannot give him breastmilk. ” A Buddhist participant also added: “Our breast is the best source of breastmilk and baby needs breastmilk. It is the nature of women to give breastmilk and we cannot do this if we have no breasts…it causes us not to be able to do a good mothering role”.Losing breasts was a great concern, especially among those who had babies, as they would be unable to breastfeed their babies. They would feel guilty about this since they could not perform a good mothering role like others. Kaja, a Muslim woman stated: “It is not stigmatised at all…just our health is not the same. But one can live a normal life, although living with just one breast”.However, many pointed out that having breast cancer nowadays was not a stigmatised condition as women would receive empathy and support from others. The nature of being a woman would not have disappeared although they had one or no breasts. So, they could continue their normal life as it was. Sane, a Muslim woman, said: “Our community forms good culture. We help each other and care for each other. We give mental support and wish them for recovery when [one] faces a hard time in life.” Rana, a Buddhist woman, added: “We will visit if one gets illness for sure. We don’t leave them behind. Even during the COVID-19 outbreak, we would visit and at least give some support in different forms  and this helps”.All participants pointed out that the nature of living in a rural setting where people had close relationships with others, including their relatives and neighbors, allowed them to visit and support each other as part of their daily lives. When community members faced difficulties, they received support to enable easier living and encouragement to continue their lives. The participants shared that this unique character of mutual support would develop more during difficult times for community members. Kaja remarked: “Yes, if detecting quickly, it can be treated quickly. Some persons may not check their breasts regularly, they might get disease easily”. However, a few women felt anxious if they had to perform self-breast screening as they might detect some abnormal signs, and this would lead to fears. Thus, they avoided touching their breasts. Samami said: “I am afraid of breast cancer and try not to think about it including worry if [I] have to do breast self-examination. If I did it, [I] fear of feeling the lump”.Breast screening was seen by most women who participated in our study as an important means to detect breast cancer and reduce the severity and complications of the disease. They understood that screening could detect abnormal signs earlier which would allow them to seek proper treatment and have a higher chance of recovery compared to those who had never followed screening practices. Samon, a Buddhist, pointed out: “All women prevented ill health by engaging in low-risk behaviours for developing breast cancer, such as consuming organic products and growing their own vegetables. They tried to adopt positive behaviors, such as avoiding crowded communities as it created stress and pollution, keeping away from smoking, and taking raw food. They believed that following such positive practices could reduce the possibility of breast cancer development.like a bottle, I can use a lid to cover and it can prevent bugs or ants from getting into the bottle, but breast cancer is not like that. We don’t know when germs will intrude into our cells or which route, so how we can prevent it? Thus, although we knew that breast screening is important, it does not always help”. She also elaborated:However, individuals’ beliefs and perceptions could be barriers to regular screening. Several participants thought that breast cancer could not be prevented. They believed that life was unpredictable, and people would never know what would happen to them in their everyday lives. Ka Sha, a Muslim participant, said: “How can we prevent it because it tends to show signs when it has seriously infected and no way to cure it, just has to do mastectomy only … If part of our body is damaged or infected, it has to follow proper treatment.I have never done self-breast screening properly. The disease has not happened yet and it is very rare to occur in younger women like us.” Apinya, a Buddhist woman, stated:Many younger women did not believe that they would have breast cancer in life. They perceived that breast cancer was found only in older women. From their experience, this disease tended to occur among women aged between 50 and above. Thus, they assumed that they would have a low risk of getting breast cancer and did not pay much attention to the prevention of breast cancer. They did not search for any information about breast cancer screening programmes and practices. Yanee, a Muslim woman, stated: “[I] am just 33 years old now and have not thought about it. Most [breast cancer] is found in older women, so I never search for information about breast cancer and have never been interested to look for such information. [I] don’t know how to do breast screening. [I] have never thought I will get this disease as I am still young.[I] am not confident at all. I just touch slightly like this while showering and cannot feel anything I am a bit worried though.” Nee further stated:All participants understood that screening was a basic technique for the early detection of breast cancer. Training sessions and follow-up activities were provided by healthcare professionals once a year. Many women pointed out that they could follow screening procedures during the training activity, but they did not feel confident when they had to do it on their own at home. They wanted healthcare providers to check their breasts more than once a year because this was the best means to determine whether they had the risk of developing breast cancer or not. They remarked that, if they were left to do it on their own, it might be too late to detect the disease at an early stage because they were not confident if they performed the right detection technique or not. Kaja said: “Healthcare providers in the local area teach us how to do self-screening. They said we can do it while showering, but [I] don’t know how deep or hard we have to press on the breast. Sometimes, we did not press hard enough and stop when feeling pain. so, I am not sure if I perform it correctly or not.Some participants paid little attention to breast health promotion and prevention. This is because they did not believe that they would get breast cancer. They then overlooked information and knowledge about breast health screening, campaigns, and prevention activities. As they had to attend to their everyday life activities and responsibilities, they saw disease prevention and self-care promotion as a future priority.I feel embarrassed. I have to open my breast naked. I am terrified of showing my private organ. It is bud see (embarrassment or sham)”. But Siri, a Buddhist woman, pointed out: “I am not so shy. I am not a young woman and have three children. It also has a curtain while screening. Then it’s okay.”Importantly, many women, particularly Muslim women, felt shame to be screened by healthcare staff because they had to unclothe while screening. They considered the breast as a private part of individuals. Rana, a Muslim woman, stated: “At the beginning, I have not thought about breast detecting. I do concern more when my father was diagnosed with cancer. I check it more often and touch if any lymph around breast”.Many participants informed us that they had no concerns about breast screening because no family members had been diagnosed with any kind of cancer before. However, for those who had family members with cancer, this led them to have more concern about screening for early detection. They spent time checking their health and performed breast cancer screening more often. Wanna who just recently had a father diagnosed with cancer pointed out: “The majority of women who participated in this study perceived that there were many risk factors causing breast cancer: genetics, individual health behaviour, family member history, age of menopause, history of abnormal breasts and environment, for example. Individuals could experience breast cancer at any time during their lifetime as a result of these factors. This is in accordance with Morman et al.  who suggBreast screening is well-accepted worldwide as a widely adopted means of early breast cancer detection ,25. EarlIt was revealed in our study that most participants did not feel confident that breast screening was the best means for early detection or prevention of advanced breast cancer prognosis. They believed that they could not control or avoid diseases and illnesses because it depended also on the visions of Allah and the rule of karma as a result of actions they had performed. Their life was dictated by Allah and karma. This is in line with Liamputtong and Suwankhong’s study . Due to Many participants in this study paid little attention to seeking information and gaining knowledge about breast cancer. In addition, they showed less awareness about the risk of breast cancer. This may be because of a low perception of susceptibility to disease. According to the HBM, Rosenstock et al. and Skinner et al. articulated that perceived susceptibility is related to how individuals perceive a threat, and this predicts how individuals behave for their health ,21. It iTraining for self-screening from health care providers is required regularly to ensure individuals’ skills and practice. We found that many women in our study had no confidence in self-examination. Skill training opportunities were organized by healthcare providers only occasionally. Receiving irregular training and follow-up reduces women’s awareness of breast cancer and likelihood of performing screening as part of their daily lives. This finding is in contrast to the findings of a study conducted by Haghbeen et al., who argued that individuals believed in the benefit of breast self-examination, they would have high level of awareness of prevention practice procedures and have fewer barriers to doing so. They would have increased self-efficacy for breast self-screening .Beliefs and perceptions influence how individuals make decisions about health practices and behaviour . Many paInterestingly, we found a marked difference regarding religious beliefs between Muslim and Buddhist groups when the participants were asked about the likelihood of developing breast cancer in their life. Islam and Buddhism have influenced how people lead their lives and behave regarding their health. Muslim women in our study had a strong belief in the influence of God (Allah), whereas Buddhist women tended to refer to their own karma. Yew et al. described the important aspect of Islam as the belief in a God or Allah . The deeTo our knowledge, this study is the first research project carried out in a rural community which considered a multicultural site in southern Thailand. The findings add to the literature in the area of health promotion and prevention, particularly with regard to women’s health. In rural communities in developing countries, there are insufficient healthcare facilities to support optimal health. The findings of our study could enable health professionals in the locality to be more aware that there are many at-risk groups of women in the rural community who do not pay sufficient attention to promoting breast health and preventing risk factors. Many barriers exist. This can increase the risk of developing advanced breast cancer among women in the nation. Thus, it is essential to pursue proactive actions to boost individual’s awareness of breast self-examination. The collaboration of all sectors in the community can strengthen breast health prevention and promote it as a key activity of the community. This could increase women’s awareness, leading to sustainable practice among at-risk groups of women.The implications for future healthcare and research of the study include that healthcare settings in multicultural communities should pursue activities to enable at-risk women to have a platform to share their perceptions, beliefs and practices about breast cancer. These activities should be run either through health leaders in the community or village health volunteers (VHVs) to provide support, as well as to remind women about breast self-examination. These activities should be organised twice a year and become routine practice in healthcare settings. Moreover, it is important that means are provided for women to access health information using user-friendly technology and media as this can increase ease of access to necessary health information. Online applications, for example, are recognised as appropriate options in the 21st century as they involve use of real-time media, which can encourage people to take part in interactive communication for health consultation if needed. Such activities can be established based on individual health record data for disease prevention. Further research that uses quasi-experimental designs to develop health technology and media for women in multiethnic communities to increase their literacy and accessibility to breast health promotion and prevention is recommended.However, the study has limitations. As a qualitative study, it provides insights and understanding about perceptions of breast cancer and screening prevention programmes amongst women, but the results of this study might not be applicable to women living in other social contexts in Thailand.Breast cancer remains a public health problem in Thailand as it is the leading cause of death among Thai women today. Women in this study perceived that there were various factors causing breast cancer: genetics, individual behaviour, environment and religious beliefs. They perceived that a woman had a chance of developing breast cancer during their lifetime. Although they understood that early detection through breast self-examination was a basic technique to help check abnormal signs, most women were not confident that this could indicate breast cancer at an earlier stage. They had no confidence in performing breast self-examination. They trusted public healthcare workers at local health centres to perform this for them more often because of their professional skills. To prevent the risk of developing breast cancer among at-risk groups in the local community, regular breast self-examination to increase individual skills needed to be managed properly. This could be undertaken in parallel with regularly organised community activities in local areas. Public health providers need to be more concerned about perceptions, beliefs and practices regarding breast cancer and develop prevention practices that work better for women living in more diverse cultural locations so that they may be able to follow preventive practices and reduce their vulnerability to breast cancer.


Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown.Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants.Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes.Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical implications for women who undergo genetic testing and be pivotal for a substantial proportion of breast cancer patients in Cyprus. Germline pathogenic variants (PVs) in cancer susceptibility genes have been associated with a significant risk of breast cancer . FollowiATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, TP53), of which the most prevalent occur in BRCA2, CHEK2 and BRCA1  BRIDGES project , to inven = 158/973) and 8.0%  for cases and controls, respectively. The majority of tumors were invasive carcinomas , estrogen receptor (ER)-positive , progesterone receptor (PR)-positive  and human epidermal growth factor receptor 2 (HER2)-negative . Out of the 990 tumors, 576 (58.2%) had available data for all ER, PR and HER2, of which 11.5% (n = 66/576) had a triple-negative phenotype, 76.6% (n = 441/576) had an ER + phenotype, 62.8% (n = 362/576) had a PR + phenotype and 16.1% (n = 93/576) had a HER2+ phenotype. All study sample characteristics are summarized in This study included case-control samples from the MASTOS study, a population-based case-control study of breast cancer in Cyprus . The stuPPM1D was shown to be associated with breast or ovarian cancer risk, but in low allelic fractions (“somatic mosaicism”)  . These aaicism”) . In-framATM, BARD1, BRCA1, RAD51C, RAD51C and PALB2 for which the truncated protein might still be pathogenic, irrespective of exon skipping; evidence previously documented  were excluded, since they are of uncertain clinical significance according to ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) classification schemes (Protein-truncating variants (PTVs) were defined as frameshift insertions/deletions, splicing variants (±2 positions) and nonsense variants as annotated by ANNOVAR . Splice cumented ), as welcumented . In addi schemes .https://www.ncbi.nlm.nih.gov/clinvar/, last accessed 11/12/2022), or the ENIGMA BRCA1 and BRCA2 expert panel (https://enigmaconsortium.org/) . Rare missense variants classified as (likely) benign were not considered in the analysis.Classifications for rare missense variants  were retrieved from ClinVar (um.org/) , along widelines , augmentidelines . Rare mip values were estimated using Wald’s test. p values smaller than 0.05 were considered to be statistically significant. Association analysis was performed separately for PTVs and rare missense variants. Associations for rare missense variants were also evaluated according to gene and gene domain for the established breast cancer susceptibility genes  with 95% CIs were estimated using Firth’s bias-reduced penalized-likelihood logistic regression for overall, ER-positive and ER-negative breast cancer. For ER-negative cases, we also evaluated the associations for triple-negative breast cancer. Associations were adjusted for age at diagnosis or interview and first-degree family history of breast cancer. Logistic regression ty genes . HeterozCumulative risks of breast cancer in the absence of other events were calculated by combining age-specific odds ratios with population incidence rates for Cyprus (2020) as a baseline, as previously described .All the protein-truncating and rare missense variants are provided in n = 16/1,094) of controls (n = 35/990) and 0.37% of controls , harbored PTVs in the established breast cancer susceptibility genes ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D and TP53  of cases and 1.46% , ATM , PALB2 , RAD50 , BRCA1  and FANCC . We also identified one PTV in each of RECQL, ABRAXAS1 and MUTYH. Among controls, the highest prevalence was observed for RECQL  and FANCC . We also detected one PTV in each of ATM, BRCA1, BRCA2, CDH1, CHEK2, FANCM, GEN1, MRE11, MUTYH, RAD50 and RINT1 (BRCA2 c.8756delG PTV was detected in 1.01% of breast cancer cases (n = 10/990) and 0.09% of controls  which corresponds to more than half of the BRCA2 PTVs observed among cases  and the only BRCA2 PTV identified among controls.Among the case patients, the highest prevalence of PTVs was observed for nd RINT1 . The fouBRCA2 and ATM with adjusted ORs of 9.75  and 7.61  , although not statistically significant  . Associanificant . For othificance .BRCA1 and BRCA2 had a relatively younger age at diagnosis (46.7 ± 10.4 sd) compared to cases without PTVs in BRCA1 and BRCA2  or cases with PTVs in genes other than BRCA1 and BRCA2 . The associations with breast cancer overall for both participants diagnosed or recruited at an age earlier or later than 50 years did not reach statistical significance, except for BRCA2 PTV-carriers who were at an increased risk of the disease if diagnosed at an age later than 50 years (n = 13/158) was about two times the frequency reported among patients with no family history of breast cancer . To investigate the influence of a family history of breast cancer, analysis was conducted separately for cases with and without a first-degree relative with breast cancer. Among participants with family history of breast cancer, PTVs in ATM , BRCA2 , BRCA1 , PALB2  and RAD50  were significantly associated with increased risk of breast cancer. The exclusion of breast cancer patients with a family history of breast cancer had a minor impact on PTV association with overall breast cancer risk   .BRCA2 were strongly associated with an increased risk of ER-positive and triple-negative breast cancer with adjusted ORs of 10.18  and 10.14 , respectively. Protein-truncating variants in BRCA1 were strongly associated with an increased risk of ER-negative breast cancer with adjusted ORs of 20.73 . Protein-truncating variants in ATM were associated with an increased risk of both ER-negative and ER-positive disease with adjusted ORs of 12.55  and 7.47 , respectively. Finally, PTVs in the PALB2 gene were associated with an increased risk of ER-negative breast cancer with adjusted ORs of 44.23  (Protein-truncating variants in = 0.021) .BRCA2 with ORs of 0.94   surveillance screening guidelines (Odds ratios decreased significantly with increasing age for = 0.013) . Estimat= 0.013) . For caridelines .n = 499/990) and 41.77% of controls   . Of thesBRCA1 were associated with an increased risk of overall breast cancer with an adjusted OR of 2.4   and 2.77 , respectively  . In the ectively . IncreasBRCA1 Zinc-Finger, ATM FAT, PALB2 WD1 and CHEK2 FHA domains. In addition, rare missense variants within the ATM PI3L/PI4K catalytic domain demonstrated an association with an increased risk of ER-positive disease. Furthermore, rare missense variants within PALB2 domains WD1, domain for stimulation of POLH DNA synthesis and domain for interaction with RAD51, BRCA2 and POLH were significantly associated with increased risk of triple-negative breast cancer. Detailed results from the domain-specific analysis are shown in For missense variants in aggregate, the evidence for an association between overall breast cancer and any protein domain did not reach statistical significance. However, there was a significantly increased risk of ER-negative breast cancer associated with variants located within the This study evaluates the prevalence of protein-truncating and rare missense variants in putative breast cancer susceptibility genes and estimates population-specific risks of breast cancer in a large case-control dataset of breast cancer in Cyprus. We used panel sequencing data from 990 breast cancer cases unselected for family history of breast and/or ovarian cancer or age at disease diagnosis and 1,094 age-matched controls, generated as part of the Breast Cancer Association Consortium (BCAC) BRIDGES project .BRCA2, CHEK2, BRCA1 and ATM , with the founder BRCA2 c.8756delG PTV being detected in ten breast cancer cases (1.01%) which corresponds to more than half of the BRCA2 PTVs observed among cases. Furthermore, BRCA2 PTVs were associated with a high risk of breast cancer overall, ER-positive and triple-negative disease and exceeded the 80-year cumulative risk threshold for high risk (30%), as defined by the NICE surveillance screening guidelines ((NICE) 2019). The cumulative risk estimates for BRCA2 PTVs in Cyprus are higher compared to risks reported by population- . However, BRCA1 was associated with an increased risk of ER-negative disease and was identified as a high-risk gene among case patients who had a first-degree relative with breast cancer. Moreover, breast cancer patients with PTVs in BRCA1 and BRCA2 had a relatively younger age at diagnosis compared to cases without PTVs in BRCA1 and BRCA2 or cases with PTVs in genes other than BRCA1 and BRCA2. These findings are consistent with recent data suggesting that the prevalence of PVs in genes other than BRCA1 and BRCA2 does not depend on age at diagnosis  2019], compared to published moderate-risk estimates for ATM PTVs  and ER-negative disease (p < 0.05). However, among cases with a family history of breast cancer, PTVs in PALB2 were significantly associated with a high risk of disease (p < 0.05), a finding consistent with reported associations  account for around 30%–40% of the total number of variants identified in gene-panel sequencing studies . Among aBRCA2 and ATM PTVs with overall breast cancer risk, and ER-negative breast cancer for PALB2 PTVs. Among the established breast cancer susceptibility genes, the most prevalent PTVs occurred in the BRCA2 and ATM, followed by PALB2, and BRCA1. Finally, we confirm the effect of family history, age at diagnosis and tumor subtype as critical factors important for risk stratification of women with breast cancer in the general population of Cyprus. These results, in combination with other risk factors, may have important clinical implications for women who undergo genetic testing for breast cancer susceptibility and be beneficial for a substantial proportion of breast cancer patients in Cyprus.Overall, we report that 3.54% of breast cancer cases in Cyprus are positive for PTVs in the established breast cancer susceptibility genes. We further provide population-specific evidence for the association of


Healthy diet, based on “healthy diet score,” was determined according to fruit, vegetables, grains, fish, and meat consumption. We compared adherence to healthy diet and the risk of UGI cancer. We also constructed a UGI polygenic risk score (UGI-PRS) to assess the combined effect of genetic risk and healthy diet. For the results high adherence to healthy diet reduced 24% UGI cancer risk , p = 0.009). A combined effect of high genetic risk and unhealthy diet on UGI cancer risk was observed, with HR reaching 1.60 . Among participants with high genetic risk, the absolute five-year incidence risk of UGI cancer was significantly reduced, from 0.16% to 0.10%, by having a healthy diet. In summary, healthy diet decreased UGI cancer risk, and individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy diet.Dietary and genetic factors are considered to be associated with UGI cancer risk. However, examinations of the effect of healthy diet on UGI cancer risk and the extent to which healthy diet modifies the impact of genetic susceptibility on UGI cancer remains limited. Associations were analyzed through Cox regression of the UK Biobank data ( Upper gastrointestinal (UGI) cancer, including esophageal cancer (ESC) and gastric cancer (GC), account for 1.7 million new cancer cases and 1.3 million deaths each year worldwide  and alcoIt was estimated that 5.1–5.9% of cancer cases each year worldwide can be attributed directly to poor diet . Rather Accumulating evidence has shown that genetic factors have major roles in the development of UGI cancer ,20. ReceIn this study, we conducted dietary pattern analysis based on examining the adherence to healthy diet and investigated the association of adherence to healthy diet with UGI cancer risk using UK Biobank data. We also tested the hypothesis that dietary factors and genetic factors jointly contribute to incident UGI cancer and that adopting a healthy diet can attenuate UGI cancer risk for individuals at high genetic risk.n = 46,531), those who were missing any dietary information data , and individuals who had withdrawn consent for future linkage (n = 157), leaving 415,589 participants  included in the study. First, we examined the association between the degree of adherence to healthy diet defined by healthy diet score and UGI cancer risk. Then, we compared the combined effect and interactions of healthy diet and genetic risk categories on UGI cancer risk across genetic risk groups. Last, we compared the benefit of adherence to a healthy diet within genetic risk groups  Red meat intake, (2) Total fish intake, (3) Total vegetables intake, (4) Total fruit intake, (5) Whole grains intake, and (6) Refined grains intake. We summed beef, lamb and pork intake to create red meat intake. We also summed oily fish and non-oily fish intake to generate total fish intake. To calculate total vegetables and fruit consumption respectively, we aggregated cooked vegetables and salad/raw vegetable intake as total vegetables intake, and fresh fruit and dried fruit as total fruit intake. We divided grains into whole grains and refined grains according to the type of bread and cereal mainly consumed. We defined wholemeal or wholegrain bread, bran cereal, oat cereal, and muesli as whole grains; white bread, brown bread, other bread, biscuit cereal, and other cereals as refined grains. We categorized the 12 food items into 7 food groups, including red meat, processed meat, total fish, total fruit, total vegetables, whole grains and refined grains. We also defined serving size for each baseline food items. For bread and cereal, data were provided for weekly consumption, which were converted into daily consumption. Detailed serving size and coding for each food item/food group are shown in We adopted seven dietary factors and cut-offs according to recommendations for dietary priorities on cardiometabolic health , that isp < 5 × 10−8 and minor allele frequency (MAF) ≥0.01 from GWAS with the largest sample size in European ancestry [r2 > 0.8) were included in the present study. If more than one variant correlated in the same locus were reported, the SNPs with the smallest reported p-value were selected by using the linkage disequilibrium clumping procedure (at r2 < 0.2) in PLINK. We excluded SNPs with allele mismatches or MAF differences > 0.10, compared with those in the European population of 1000 Genomes, and palindromic SNPs  with an MAF ≥0.45. Finally, we estimated site-specific PRS based on 13 SNPs and 3 SNPs for ESC and GC, respectively (r2  >  0.6) with each other in more than one site-specific PRS. Firstly, site-specific PRS was created following an additive model [Genotyping process and single nucleotide polymorphisms (SNPs) used in the UKB research have been described elsewhere in detail ,32. We eancestry ,33. For ectively . No SNPsve model , generatve model . Cancer ve model ,37. The The outcomes in the study were first primary incident events due to UGI cancer (ESC and GC), which is identified through the national cancer registries of England, Wales, and Scotland, coded by the 10th revision of the International Classification of Diseases (ICD-10), as (C15) and (C16) for ESC and GC, respectively. After four years of baseline recruitment (2006–2010), UGI cancer risk in participants was assessed from baseline up to the UGI cancer diagnosis, death, completion of follow-up, or loss to follow-up, whichever occurred first. The time of risk was calculated according to date the participant attended the assessment center (Data Field: 53), date of cancer diagnosis (Data Field: 40005) and the end date of follow-up. The end date of follow-up was updated to September 2018 for Scotland and to June 2021 for England and Wales. For participants who developed a UGI cancer, time at risk was the interval between the date of cancer diagnosis and the date of attending assessment. For participants without UGI cancer, time at risk was calculated by the end date of follow-up minus date of attending assessment center.Cox proportional hazard models were used to investigate the associations between healthy diet and UGI cancer risk and to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) with the time of follow-up used as the timeline variable. The proportional hazard assumptions were checked using Schoenfeld residuals. We determined UGI cancer risk for participants among healthy diet score categories . We also compared the UGI cancer risk for per two-point increase in healthy diet score. Furthermore, we investigated the combined effect and interactions of dietary and genetic factors on UGI cancer risk according to healthy diet and genetic risk categories to explore the extent to which healthy diet modified the associations between genetic susceptibility and UGI cancer risk across genetic risk groups. We examined the results for potential additive and multiplicative interaction between healthy diet and genetic risk . The add2, <25, 25–29.9, ≥30), glycosylated hemoglobin , smoking status , alcohol intake frequency , education , multimorbidity , physical activity  [Two models were applied in our analyses: minimally adjusted model, adjusted for age at recruitment, sex, Townsend deprivation index, assessment center (10 regions) and ethnic background; fully adjusted model, additionally adjusted for BMI (kg/mes/week)  and famin = 41,292); (2) excluded participants followed up for less than two years (n = 1648); (3) excluded non-white participants .We performed the following sensitivity analysis to further investigate the robustness of our results: (1) excluded participants who reported that they had made a major change in their diet in the past 5 years due to illness in the past 5 years . All 2. Of all participants, the 16.99% with UGI cancer were current smokers, and 23.18% UGI cancer participants consumed alcohol at least three times per week. The 414,200 participants  had a mean (SD) BMI of 27.39 (4.75) kg/m2 without UGI cancer. A total of 10.25% participants with UGI cancer were current smokers, and 18.29% UGI cancer participants consumed alcohol at least three times per week.A total of 415,589 participants (53.54% women) had available dietary data of this study. The median follow-up period was 12.12 (interquartile range: 11.32–12.84) years for UGI cancer incidence. A total of 1389 UGI cancer developed during the period, including 564 GC and 831 ESC. The baseline characteristics of participants are shown in p = 0.009). Having a two-point increase in healthy diet score was associated with a higher UGI cancer risk, with HR of 0.90 . Similar results were noted in a series of sensitivity analyses , when compared with participants with a healthy diet and low genetic risk . The standard error shrinks as the sample size increases; in a very large sample, the standard error becomes very small, which leads to a statistically significant distance between the estimate and the null hypothesis that may be negligible. Therefore, to reduce type I errors, the null hypothesis cannot be rejected by the p-value alone in a large sample study. These problems can be solved by additionally reporting effect sizes and 95% confidence intervals (CI) [p values to more cautiously infer the association between healthy diet and UGI cancer.UK Biobank is a large, general population-based prospective cohort, which provides health outcomes and a wide range of potential confounders, including diet. One of the inevitable problems with large sample studies is that als (CI) . In our The present study has several limitations. First, participants in the UK Biobank are of European descent; therefore, the summary statistics should be generalized to the general population with caution. Secondly, the use of self-reported recall of FFQ could introduce some level of recall bias. Third, it is generally accepted that associations between nutrients and disease should only be considered primary if the effects are independent of energy intake . We wereOur findings confirm and broaden the results from previous studies. Healthy diet was associated with a lower risk of UGI cancer. Dietary factors and genetic risk had a combined effect on risk of UGI cancer. Individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy dietary pattern.