TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. In the present study, we sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population.Tumor necrosis factor-α (TNF-α) plays a crucial role in the development and progression of gastric cancer. A functional polymorphism, -308 G>A (rs1800629), which is located in the promoter of TNFA -308 G>A polymorphism using the TaqMan method in a two-stage case-control study comprising a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The logistic regression was used to assess the genetic associations with occurrence and progression of gastric cancer.We genotyped the P = 0.034, odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.01–1.67, GA/AA vs. GG]. Similar results were observed in the follow-up replication study. When combined the data from the two studies, we found a more significant association , especially for older subjects (>65 years). Furthermore, the patients carrying the variant genotypes had a significantly greater prevalence of T4 stage of disease  and distant metastasis .We found a significant association between the variant genotypes and increased risk of gastric cancer [TNFA influence the susceptibility and progression of gastric cancer in the Chinese population.Our results suggest that the functional promoter -308 G>A polymorphism in  Helicobacter pylori (H. pylori) infection, are well-known causes of gastric cancer Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide, and particularly prevalent in certain countries, including China H. pylori infection is a critical step in the development of gastric cancer H. pylori infection is the tumor necrosis factor (TNF) –α which is encoded by the TNFA gene It has been suggested that chronic inflammation in gastric mucosa induced by the TNFA gene is located within the human leukocyte antigen class III region on chromosome 6 (6p21) and is highly polymorphic. Polymorphisms in the TNFA gene have been shown to greatly influence its expression level TNFA could be used as putative determinant factor of susceptibility for various diseases, including gastric cancer. Among the many polymorphisms in TNFA promoter, the TNFA-308 G>A polymorphism were wildly studied and there is functional study suggesting that the -308A allele is associated with increased TNF-α production TNFA-308 G>A polymorphism and gastric cancer in various populations, however, the results form these studies remain inclusive TNFA -308 G>A polymorphism on gastric cancer risk and progression in a Chinese population.The The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. At recruitment, written informed consent was obtained from all participants involved in this study.This is an ongoing molecular epidemiologic study of gastric cancer conducted in the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. The design of the study and the inclusion criteria of the subjects were previously described elsewhere TNFA -308 G>A polymorphism was genotyped using the TaqMan-MGB method , which uses two allele-specific TaqMan MGB probes and a PCR primer pair to detect the specific SNP target. The sequence of the primers and probes are available on request. The reaction mixture of 10 µL contained 20 ng genomic DNA, 3.5 µL of 2× TaqMan Genotyping Master Mix, 0.25 µL of the primers and probes mix and 6.25 µL of double distilled water. The amplification was performed under the following conditions: 50°C for 2 min, 95°C for 10 min followed by 45 cycles of 95°C for 15 sec, and 60°C for 1 min. Following the manufacturer's instructions, amplifications were conducted in the 384-well ABI 7900HT Real Time PCR System  and the allelic discrimination were performed using the SDS 2.4 software . The genotyping rates of these SNPs were all above 98%. To ensure the accuracy of genotyping, two negative experimental control (water) and two positive experimental controls with known genotype were included in each reaction plate. In addition, about 5% of the samples were randomly selected for repeated genotyping for confirmation; and the results were 100% concordant.The whole genomic DNA was isolated and purified from leucocytes of peripheral blood by proteinase K digestion and phenol/chloroform extraction. The TNFA -308G>A polymorphism in the controls of test set, validation set and combined set were assessed against departure from Hardy-Weinberg equilibrium (HWE) using a goodness-of-fit χ2-test. Differences in the distributions of age, sex and frequencies of genotypes of the TNFA -308G>A polymorphism between the cases and controls were evaluated by Pearson's χ2 test. The associations between the -308G>A genotypes and risk of gastric cancer as well as the clinical characteristics of the patients were measured by computing odds ratios (ORs) and 95% confidence intervals (CIs) from unconditional logistic regression analysis with the adjustment for age and sex. All the statistical analyses were performed with the software SAS 9.1.3  and a two-side P value of less than 0.05 was considered as statistically significant.Before further analysis, the allele frequencies of P = 0.383 and 0.424 in the test set and P = 0.164 and 0.061 in the validation set, respectively). Although more older subjects (>65years) and female subjects were presented in the test set than in the validation set, no significant difference in age and sex between the cases and controls was observed when we combined the two populations . We then used Pearson's χ2 test and logistic regression analysis to assess the association between TNFA -308 G>A polymorphism and gastric cancer risk. In the test set, we found that there were more variant genotypes (GA/AA) in the case group than that in the control group (P = 0.034). Compared with the individuals with GG genotype, we found those subjects with GA/AA genotypes had an increased risk of gastric cancer . Similar associations were observed in the replication study . When we combined data from the two studies, a more significant association was observed .The genotyping results of the TNFA -308 G>A polymorphism plays different role in subgroups of age, sex, tumor site and histological types, we then performed stratified analysis based on these variables. As shown in TNFA -308GG/GA genotypes was more evident among older subjects (>65years) . Besides, no significant difference was observed in the stratification of sex, tumor site and histological types.To evaluate if the TNFA -308 G>A polymorphism has effects on the clinical characteristics of the patients, including TNM stage, distant metastasis, lymph node metastasis and depth of tumor infiltration. As shown in P = 0.001, OR = 2.19, 95%CI = 1.39–3.47) and distant metastasis , indicating the polymorphism might be associated with gastric cancer progression.Polymorphisms in candidate genes have been suggested to influence cancer progression. We then evaluated whether the TNFA -308 G>A polymorphism and gastric cancer risk and progression. TNF-α is an important immune mediator in inflammatory response and has been suggested to be an endogenous tumor promoter in human carcinogenesis et al. demonstrated that TNF-α mRNA and protein expressions were significantly increased in gastric adenocarcinoma patients, by using RT-PCR, western blotting and immunohistochemistry TNFA has been previously investigated. Karen et al. showed that the -308G>A polymorphism could affect the affinity of factor binding and result in a factor binding to the -308A allele but not the -308G allele, which then lead to an increased expression of TNFATNFA -308G>A confers individuals' susceptibility to gastric cancer.The main findings of our study are the significant associations between the TNFA -308G>A polymorphism and gastric cancer risk. However, the results from these studies remain inconclusive. There are two published meta-analyses on the associations between the TNFA -308G>A and gastric cancer risk that have identified this polymorphism as a risk factor for gastric cancer in Caucasian populations but not in Asian populations et al.et al.et al. found a significant association between TNFA -308GA genotype and increased risk of gastric cancer risk . Our study further identify the TNFA -308G>A polymorphism as a risk factor for gastric cancer in Chinese population, which may be of value in evaluating the role of TNF- α in gastric carcinogenesis. As indicated by Power and Sample Size Calculation software, our study had a 96% power to detect an OR of 1.50 or greater and a minimal OR of 0.62 with an exposure frequency of 9% at the current sample size (1686 cases and 1895 controls), which suggests that the sample size of our study is efficient.To date, several molecular epidemiological studies have been conducted to investigate the association between the TNFA -308G>A polymorphism was associated with increased risk of gastric cancer among subgroups of older subjects (age>65 years) rather than younger subjects. This observation is well supported by a large body of studies, which link weak immune system with ageing TNFA -308G>A polymorphism was associated with clinical aggressiveness such as advanced tumor stage and distant metastasis. Similar observation has also been reported in other study In addition, we found that the H. pylori infection status is a well-known cause of gastric cancer and has been suggested to influence the expression of TNF- α TNFA may interact with this factor to affect gastric caner risk. Unfortunately, lack of available information on H. pylori infection status in our study limited us to further explore these interactions. Thus, further studies with more detailed data on H. pylori infection are warranted.When interpreting our results, some other limitations should also be concerned. First, since our study was hospital-based design, the possibility of selection bias of subjects that were associated with a particular genotype might exist. However, the genotype distributions in our controls were similar to distributions reported in other Chinese studies and conformed to HWE. Therefore, the selection bias in terms of genotype distributions would not be substantial. Second, TNFA has a significant influence on the occurrence and progression of gastric in the Chinese population. Although the associations appeared to be statistically significant in our population, these findings should be independently verified by other prospective studies with larger sample size simultaneous of well-matched controls and unbiased-matched homogeneous participants.In conclusion, our results suggest the -308G>A polymorphism in the promoter of


Western breast cancer survivors have an increased risk of osteoporosis and bone fracture. Breast cancer occurs 10 to 20 years earlier in Asian women than in Western women. We investigated if younger Asian women with breast cancer also have increased risk of fracture.We used the universal insurance claims data from 2000 to 2003 to identify 22,076 patients with breast cancer and 88,304 women without cancer, frequency matched with age and index date . The incidence of fracture in both cohorts and the hazard ratios (HRs) of fracture in the cancer cohort were estimated by the end of 2009.The incidence of all types of fracture was higher in the breast cancer cohort than in the comparison cohort , with adjusted HRs (aHRs) of 1.18  for hip fractures, 1.12  for forearm fractures and 1.24  for vertebral fractures. The aHRs were significant in both non-traumatic fractures  and traumatic fractures . The age-specific aHR was higher for younger breast cancer patients, and was significant for <50 years old patients in both traumatic  and non-traumatic  fractures.This study suggests that Asian women with breast cancer might have an increased risk of fracture. Both breast cancer and osteoporosis are disorders primarily associated with aging in women, and have been a medical challenge worldwide. Osteoporosis and the associated fractures have become important global public health issues. Almost 56 million people were diagnosed with various types of fracture in 2000, with approximately 9 million new osteoporotic fractures occur annually http://www.nhi.gov.tw). This study used the inpatients dataset and catastrophic illness dataset established by the National Health Research Institutes (NHRI) of Taiwan for the period of 2000 to 2009 to investigate the fracture risk in breast cancer survivors in Taiwan. We used the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to identify physician-diagnosed diseases in the claims data. This study was approved by the Ethics Review Board of China Medical University (CMU-REC-101-012).TNHI is a universal health insurance system established in 1995 by the Department of Health of Taiwan. By the end of 2010, over 99.9% (23.07 out of 23.162 million) of the population had enrolled in this program , who are free from other cancers and are aged 20 years and above in 2000–2003. The diagnosis date of breast cancer was used as the index date. Women with history of hip, distal forearm, and vertebral fracture at the baseline or those who have these types of fracture within one month after the index date were excluded from the study. A total of 21,952 women were included in the breast cancer cohort. Among the women without any cancer, we randomly selected 87,808 women as non-cancer comparison cohort, and frequency matched with age and index date . Both cohorts were followed up until the end of 2009. The subsequent fractures including the hip (ICD-9-CM 820), vertebrae  and the other type of fractures  were investigated.Data analysis first measured the annual incidence of osteoporosis-related fracture by the type of fracture in women with breast cancer. We compared the distributions of age, location of subject’s residential area and the history of non-osteoporosis fracture, between the breast and comparison cohorts. Each study subject was followed up from the index date to the event when the fracture was diagnosed, or the date censored for loss to follow-up, death, termination of insurance, or the end of 2009. The person-years of follow-up were measured for all subjects and the incidence density was estimated by per 10,000 person-years during the follow-up period. We estimated the incidence rates of fractures for both cohorts. Hazard ratio (HR) and 95% confidence interval (CI) associated with fracture were estimated using Cox proportional hazards regression analysis. The multivariable analysis model estimated adjusted HR (aHR) controlling for age at the index date , the residential area, and non-osteoporosis fracture history, etc. We also assessed the HRs of fracture among age groups to evaluate if the fracture risk was higher for a specific age group. All analyses were performed used SAS statistical package , and the significance level was set at 0.05.The baseline mean age was slightly higher in the breast cancer cohort than in the comparison cohort (51.4 (SD 12.0) vs. 51.2 (SD 12.3) years) (p = 0.02) . Higher The incidence of subsequent fractures was 1.10-fold higher in the breast cancer cohort than in the comparison cohort , with an aHR of 1.16 (95% CI 1.07–1.27) . The sitThe age-specific incidence of fracture increased with age in both cohorts, with the peak appeared in the 60–69 ages group in both the breast cancer cohort and comparison cohort . The aveRelative to the comparison cohort, the risk of all fractures in the breast cancer cohort was significantly higher in those aged <50 years  . In the Our study on breast cancer in relation to fractures yielded an aHR of 1.16 for the cancer patients versus non-cancer comparison women after controlling for covariates. The incidence of traumatic fractures was greater than that of non-traumatic fractures. But, the breast cancer cohort to comparison cohort aHR estimate was significant for non-traumatic fractures not for traumatic fractures. In a case-control study, Newcomb et al. reported women with breast cancer are 20% less likely to have the history of fracture Postmenopausal women with high bone density have an elevated risk of breast cancer However, breast cancer accelerates bone loss in patients. During natural menopause, women may suffer from bone loss for 3% per year in the earlier two years, and slows down to approximately 1% annually thereafter Chen et al. Since the early premenopausal age, these women suffer not only losing trabecular connectivity in cancellous bone structural, and cortical thinning and porosity, but also experiencing reduced toughness of bone and the resistant to crack propagation. Pores coalesce and the low bone mass cannot absorb energy radiating from a fall. Hip and distal forearm fractures occurred more frequently in the present study, and hip fracture was the worst non-traumatic osteoporosis-related fractures. Therefore, the higher risk of hip fracture in women of younger age in our study groups may be related to breast cancer.This study has several limitations. First, a few minor subclinical vertebral or wrist fractures do not systematically lead to medical management or hospitalization. The claims data also included few self-reported fractures. The incidence of vertebral fracture is low in our study and the findings are likely underestimated because of subclinical status. This inference can be verified in further analysis that compared traumatic and non-traumatic events . Women wThe 10-year overall survival of patients with breast cancer is 75% in Taiwan To the best of our knowledge, this study is the first national population-based report on fracture risk among Asian breast cancer survivors. This study suggests that women with breast cancer, particularly those diagnosed at a relatively early age, below 50 years old, should undergo prophylactic treatment to counter the increased risk of fractures.


Clinical genomics is poised for a rapid expansion but more work must be done to build a supporting ethical infrastructure. New York Times that received enormous attention around the world. She revealed that, after receiving genetic testing and counseling, she had undergone a double mastectomy. She had the surgery even though she did not have breast cancer On May 14 of this year, the actress Angelina Jolie wrote an essay in the Ironically, shortly after her decision to go public about her prophylactic mastectomy, the United States Supreme Court issued an important ruling about the patentability of the genetic test Jolie had used If clinical genomics is about to move forward at a more rapid pace due to broader public awareness and a more favorable legal climate then there is still work to be done on the ethical, regulatory, and legal fronts Perhaps the most obvious question that now arises is when is clinical genetic testing appropriate for everyone? Consider testing for breast cancer. Breast cancer is the most common malignancy in women. Approximately 200,000 women receive a diagnosis of breast cancer each year in the United States. About 40,000 women die from the disease. The five-year survival rate for women with breast cancer has been improving and is currently estimated to be greater than 85% BRCA1 and BRCA2 genes. Hereditary breast cancer syndrome is inherited in an autosomal-dominant fashion. Mutations in either BRCA1 or BRCA2 have been identified as the cause of these syndromes. Women who inherit these mutations have a significantly increased risk of developing breast and/or ovarian cancer.Approximately 5% to 10% of breast cancer cases are associated with a hereditary predisposition. Most of these cases are related to mutations in the According to the National Cancer Institute, in the general population, the incidence of breast cancer is about 0.05% per annum at age 35 and 0.2% per annum at age 50, with a cumulative lifetime risk of breast cancer of approximately 13% BRCA1 and BRCA2 mutations BRCA mutation testing only for women who have a family history suggestive of increased risk Some, often those who sell testing, argue that every woman ought to be tested for Cost has sharply limited access to testing. Jolie said she had chosen to have her breasts removed because she knew her mother and other relatives had been ravaged by breast cancer at relatively young ages. Knowing this, she had sought out genetic testing that could reveal if she was at increased risk of a hereditary form of breast cancer. She had found out, through the use of Myriad Genetics' then patented genetic test for breast cancer, that she had inherited the mutated gene and thus was at high risk for both breast and ovarian cancer. The cost of testing, which is often not covered by insurance, is not insignificant—ranging from $3,000 to $4,000. The reason for the high cost is that Myriad, the Utah-based provider of the test, has long had a monopoly over its sale Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., against Myriad Genetics and the U.S. Patent and Trademark Office Almost four years to the day before Jolie's revelation, Myriad had been the target of a highly unusual lawsuit. A variety of clinics and organizations sued, challenging the validity of patents Myriad had received for identifying the gene mutations associated with a greater risk of breast cancer. On May 12, 2009, a group of plaintiffs led by the American Civil Liberties Union and the Public Patent Foundation filed a lawsuit, BRCA genetic loci and a higher risk of breast cancer On April 15, 2013, just a few weeks before the Jolie revelation, the Supreme Court heard oral arguments about the patent case. On June 13, the Court ruled that isolated genomic DNA is not patent-eligible under section 101 of the Patent Act From an ethical point of view, striking down the claims in Myriad's patents was the right thing to do. Aside from isolating and removing genetic material, the patent merely laid claim to natural genetic sequences. This did not constitute a useful invention in that nothing was constructed, invented, or manipulated The court rightly made way for patent claims that involve manipulating genes, altering them, synthesizing new ones, or simplifying existing genes into more useful constructs. In doing so, the court secured the future of the biotechnology industry that is rapidly expanding along all of these lines of genetic research in humans, animals, plants, and microbes.The link between Jolie's decision and the patent fight settled one pressing question—can you patent what exists in nature? The decision has been hailed as opening the door to cheaper genetic testing for breast cancer and for other genetic risk factors for disease The rapid expansion of genetic testing beyond breast cancer in high-risk adults to other women would potentially not be cost-efficient given the relative rarity of the gene mutations involved in the general population but would also strain the existing resources for genetic counseling. If testing expands to include testing for many more conditions, as well as testing fetuses by blood samples drawn from pregnant women, preimplantation genetic diagnosis of embryos, newborns More widespread testing also means the discovery of more incidental but important findings. There are no agreed-upon standards about how to handle incidental clinical discoveries, which can include questions about paternity and the suspicion of incest Will testing information be coded for anonymity but in a way that still permits linkage to the identity of those tested? No agreed-upon rules exist about the morality of recontacting those who have been tested as future discoveries reveal more accurate information or new information about mitigating risk through lifestyle changes, changes in reproductive plans, or new medical therapies.If clinical genomics can now be expected to move forward more rapidly with greater legal clarity, more affordability, and more public awareness then we need:More public discussion of what level of risk would justify public reimbursement of genetic tests for whom and with what assurance of coverage for follow-up care and lifestyle coaching.Agreement among providers to set a standard of care about the precision with which informed consent will be sought as part of clinical genomic testing that includes the reliability of anonymization protections, recontacting policy, handling incidental discoveries, contacting biological relatives with results and other third parties, and the use of information for research as well as diagnostic purposes.A policy that requires clinical testing to always be accompanied by an offer of competent counseling.A commitment to train health care providers to provide counseling for testing of embryos, fetuses, carriers, newborns, and adults.Discussion of what traits and behaviors will be tested for, including an attempt to create a guideline of appropriate indications or even a diagnostic manual of clinical genomics.An articulation of regulations governing liability for the use of testing that subsequently is shown to be limited or even erroneous by subsequent genetic research.Some agreement on when direct-to-consumer advertising and recruitment of clients for diagnosis is appropriate and when it is obligatory such as for cancer patients.An examination of the adequacy of existing laws such as the 2008 Genetic Information Non-Discrimination Act, which do not cover many emerging uses of clinical genomics including the acceptability of allowing information from clinical genetic testing to be used in life, health, and disability insurance as well as in employment decisions and in setting job eligibility requirements.Since both financial and medical resources for conducting genetic testing are limited, does it make sense to concentrate on populations believed to be at greater risk of genetic diseases or should testing move rapidly toward routine testing for all? If the latter, then much more research will be needed to both broaden existing databases to include more diversity than currently exists Celebrities are now drawing public attention to the utility of genetic testing. With the Supreme Court decision opening the door to more and perhaps cheaper entry into the testing market, the requisite infrastructure for managing risk and the rules for handling risk information must be strengthened. Making testing more widely available will only be morally acceptable if there are rules of the road in place.


Additionally, we found the same tendency for the triple-negative subtype, with the OR for a 1 kg/m2 increase in current BMI of 1.21 (1.05 - 1.39) and that for BMI change of 1.18 (1.02 - 1.36) . In premenopausal women, a suggestive inverse association was observed between BMI change and breast cancer risk for the luminal subtype only, with OR of BMI change of 0.93 . No association was seen between BMI at age 20 years and risk of any tumor subtype. In conclusion, BMI and its change are associated with the risk of both luminal and triple-negative breast cancer among postmenopausal Japanese women. These findings suggest the etiological heterogeneity of breast cancer among tumor subtypes.Body mass index (BMI) is an independent risk factor for luminal-type breast cancer in Western populations. However, it is unclear whether the impact of BMI differs according to breast cancer subtype in Japanese populations. We conducted a case–control study with 715 cases and 1430 age- and menopausal status-matched controls to evaluate the associations of BMI and its change (from age 20 years to the current age) with breast cancer risk. We applied conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tumor subtypes were divided into four subtypes, namely the luminal, luminal/HER2, HER2-rich, and triple-negative subtypes. Current BMI and BMI change were positively associated with postmenopausal breast cancer risk. On stratified analysis by tumor subtype, we observed associations between current BMI and BMI change and postmenopausal breast cancer risk for the luminal subtype, with OR for each 1 kg/mThe online version of this article (doi:10.1186/2193-1801-1-39) contains supplementary material, which is available to authorized users. The rapid increase in the incidence rate of breast cancer over the last quarter of a century in Japan  can be related to changes in the prevalence of established risk factors, such as reproductive and anthropometric factors . Among these, obesity is an important and potentially modifiable risk factor for breast cancer, the incidence of which is increasing in most countries . In Japan also, body mass index (BMI) has consistently increased in older women, albeit that the prevalence of obesity remains lower than in Western countries .The association between high BMI or adult weight gain and breast cancer risk for postmenopausal women has been established, and found to be partly attributable to an increase in circulating endogenous estrogen levels from adipose tissue, the primary source of estrogen in postmenopausal women . These findings are supported by the fact that the association between BMI and risk of postmenopausal breast cancer is stronger for estrogen receptor (ER)-positive than -negative tumors .The clinical relevance of molecular subtypes of breast cancer has been demonstrated. These appear to include at least four major tumor subtypes defined by ER, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status, . Although these distinct subtypes have been associated with different clinical outcomes , evidence on etiologic differences among them is limited. Some epidemiological studies have shown that reproductive factors and BMI are associated with an increased risk of only ER- and/or PR-positive tumors , but others have suggested that ER- and PR-negative tumors are also positively associated with BMI . These studies were conducted mainly in Western populations, however, and the findings have not been entirely consistent. Additionally, potential biological differences among cancers may be present, and the prevalence of obesity differs between Western and Asian countries. These issues thus highlight the importance of evaluating the impact of BMI and its change on breast cancer risk by tumor subtype in Asian populations.Here, we conducted a case–control study to evaluate associations between BMI and breast cancer risk by tumor subtype, defined by ER, PR, and HER2 status, in a Japanese population.Case subjects were 715 female cancer patients with no previous history of breast cancer who initially visited Aichi Cancer Center Hospital (ACCH) in Nagoya, Japan, between January 2001 and June 2005. Control subjects were 1430 age- and menopause-matched females without any history of cancer, giving a 1:2 case–control ratio. All subjects were selected from the database of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), the framework of which has been described elsewhere . In brief, 23408 HERPACC-enrolled first-visit outpatients were asked to provide information on lifestyle factors and blood samples for genetic studies. Approximately 95% of eligible subjects completed a self-administered questionnaire, responses to which were checked by a trained interviewer, and 55% provided blood samples. We selected women as cases whose histological diagnosis was available and whose ER, PR and HER2 status results were confirmed. We used cancer-free patients at our hospital as controls given the likelihood that our case subjects arose within this population base. We previously showed that the general lifestyle of cancer-free outpatients at our hospital was in accord with that of a general population randomly selected from the electoral roll of Nagoya City, Aichi Prefecture, confirming the feasibility of their use as controls in epidemiological studies . The present study was approved by the Institutional Ethics Review Board of ACC, and all participants gave written informed consent.The HERPACC questionnaire included items on height and weight, weight at age 20 years, menopausal status, parity and lactation, drinking and smoking habits, exercise, hormone use, individual medical history, family history of cancer, and referral pattern to our hospital. Patients were asked to provide information on their lifestyle at one year before the onset of symptoms for those who were symptomatic, or at the time of interview for those who were asymptomatic.2) and divided into four groups, < 18.5, ≥ 18.5 to < 22, ≥ 22 to < 25, and ≥ 25. BMI at current age was referred to BMI at cancer diagnosis. Although the cut-off points of BMI for underweight/normal/overweight/obese under the World Health Organization (WHO) definition are < 18.5, ≥ 18.5 to < 25, ≥ 25 to < 30, and ≥ 30, respectively , we combined the overweight and obese groups and divided the normal group into two subgroups in consideration of the low prevalence of obesity in Japan. BMI change from age 20 years to the current age was calculated as the difference between current BMI and BMI at age 20, and was also categorized into six groups, with a BMI loss of < −4, or ≥ −4 to < −2; stable BMI of ≥ −2 to < +2; and BMI gain of ≥ +2 to < +5, ≥ +5 to < +8, and ≥ +8. Alcohol consumption was divided into never, light, moderate, and heavy drinking, with light drinking defined as consumption of less than 5 g of ethanol per day; moderate drinking as between 5 and less than 23 g per day; and heavy drinking as 23 g or more per day. Smoking habit was divided into never, former or current smoking of < 20, and ≥ 20 pack-years. Regular exercise was classified into no exercise, less than half an hour of exercise per day, and half an hour or more of exercise per day. Hormone use included all use for contraception, infertility, treatment or hormone replacement therapy. Family history was considered positive when a mother or sister had breast cancer.BMI at current age and at age 20 years was calculated as the weight divided by the squared height  staining based on the Hercep test. Tumors that showed 2+ were definitively evaluated by fluorescence in situ hybridization (FISH). Tumors were considered HER2-positive if they were either scored 3+ by IHC staining, or 2+ by IHC and were also HER2 amplified on the basis of FISH. With regard to tumor subtypes, we adopted the IHC classification described by Carey et al. , which categorizes breast cancer according to the expression status of ER, PR and HER2 as follows: luminal (ER- and/or PR-positive and HER2-negative), luminal/HER2 (ER- and/or PR-positive and HER2-positive), HER2-rich (ER- and PR-negative and HER2-positive), and triple-negative .The significance of differences in categorized demographic variables between cases and controls was evaluated using the Chi-square test. Subjects with unknown data were excluded from the Chi-square test. Mean ages were compared using the Mann–Whitney test. The effect of each BMI indicator  was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic regression models adjusted for potential confounders, namely age, age at menarche , menopausal status , parity , age at first live birth , family history of breast cancer , hormone use for contraception, infertility treatment or hormone replacement therapy , total exercise , and referral pattern to our hospital . We excluded 6 subjects (2 cases and 4 controls) with missing information on menopausal status, leaving 2139 subjects for stratified analysis by menopausal status.P value for interaction was calculated by a likelihood ratio test which compared models with and without the interaction terms.Interactions between respective BMI and menopausal status were evaluated under the multiplicative model, and the cross-product terms of these factors were included in the multivariate conditional logistic regression models as interaction terms. The P values < 0.05 were considered statistically significant.All statistical analyses were carried out using STATA ver. 11 . All tests were two-sided and P = 0.040), later first live birth among parous women , and a higher BMI . With regard to referral pattern, cases were more likely to have a family recommendation or referral from other clinics and less likely to refer at patient discretion or as part of secondary screening after primary screening. Unexpectedly, case subjects were more likely to do exercise for more than half an hour per day than controls (P = 0.029). In contrast, the other factors did not statistically significantly differ between the two groups.Table Ptrend < 0.001). Similarly, OR for women with the highest BMI change (BMI gain ≥ 8) was 2.56 (1.49 - 4.38) compared to those of women with stable BMI change (BMI change from −2 to +1.9) (Ptrend < 0.001). In contrast, no significant association was seen between BMI at age 20 years and breast cancer risk. On stratified analysis by menopausal status, current BMI and BMI change were positively associated with breast cancer risk only among postmenopausal women (each Ptrend < 0.001). We also observed statistically significant interactions between current BMI, BMI change, and menopausal status .Table 2 increase in current BMI of 1.14 (1.07 - 1.20) for the luminal subtype (Ptrend < 0.001) and 1.21  for the triple-negative subtype. Similarly, the effect of BMI change was statistically significant for the luminal and triple-negative subtypes among postmenopausal women . Further, we also found the same tendency for increased risk with BMI change after adjustment for BMI at age 20 years (data was not shown). No significant associations between current BMI, BMI change and breast cancer risk were seen for the other subtypes.Furthermore, we also evaluated the association between BMI and breast cancer risk by tumor subtype Table . As the 2 increase in BMI change of 0.93 . We were unable to assess ORs adequately among premenopausal women, particularly for the triple-negative subtype, because of the paucity of subjects. To guess the associations among them, we also showed an overall impact of BMI on risk  but not all previous studies .The biological mechanisms underlying these associations are unclear, but it is assumed that obesity influences breast cancer risk through multiple mechanisms. One is a classic estrogen-dependent mechanism, in which obesity contributes to lower serum levels of sex hormone-binding globulin and higher circulating levels of endogenous estrogen . Almost all reproductive factors that influence estrogen levels are primarily associated with luminal-type tumors, but there is also some evidence related to risk for non-luminal-type tumors . For example, our recent study in Japanese suggested that age at menarche was inversely associated with the risk of both luminal and triple-negative breast cancer . Similarly, the Polish Breast Cancer Study showed an association of earlier age at menarche with basal-like tumors only . Other mechanisms might relate to non-hormonal factors, such as an insulin-related mechanism involving insulin, insulin resistance and insulin-like growth factors (IGFs), or an inflammation-related mechanism . IGFs, which stimulate mitogen-activated protein kinase (MAPK) or Akt and increase cell survival, proliferation, and migration through signaling cascades, are also considered to be risk factors for breast cancer . Davison et al.  reported that IGFs promote cell survival in triple-negative breast cancer cells. Further, Maiti et al.  suggested that metabolic syndrome, characterized by high BMI and insulin resistance, is significantly more prevalent in triple-negative than non-triple-negative patients. On the basis of these findings, we hypothesize that the combination of these complex mechanisms contributes to an increased risk of breast cancer, particularly of triple-negative subtypes. An understanding of the etiology of less common subtypes such as triple-negative tumors, which are the most clinically aggressive, may be useful in the development of prevention strategies.Our observation of an inverse association between BMI gain and the risk of premenopausal luminal breast cancer is to our knowledge the first description in an Asian population. A number of studies have evaluate the effect of weight change on the risk of premenopausal breast cancer, but most evidence to date is from studies of ER and PR rather than HER2 disease, and the results are inconsistent . In the Nurses’ Health Study, weight loss since age 18 years was inversely related to both ER+/PR+ and ER-/PR- tumors . In contrast, a case–control study in the San Francisco Bay Area reported that inverse associations between obesity and premenopausal breast cancer risk were limited to ER+/PR+ tumors , which is consistent with our present findings. The mechanisms underlying this inverse association remain to be elucidated. Several studies have suggested that women who are obese prior to menopause are likely to have ovulatory insufficiency or anovulatory cycles, resulting in decreased estrogen and progesterone levels , and we accept this theory in interpreting our present result. However, given our limited number of subgroup subjects and the inconsistent results across studies, additional studies with sufficient numbers of subjects of various ethnicities are needed.With regard to BMI at age 20 years, we found no statistically significant association, but rather a slightly inverse association when underweight women (BMI < 18.5) were excluded . Second, the potential confounding factors of age and menopausal status were adjusted for by matching. Finally, the single-institution design of the study obviated the possibility of hormonal receptor or HER2 status misclassification resulting from different assay methods.Since the present study was based on a hospital-based case–control study, several methodological limitations exist. First, the values for self-reported life-style factors considered as potential confounding factors might have been inaccurate. In particular, information about body weight at age 20 years was collected retrospectively. Second, the classification of tumor subtypes as defined in our study is not identical to other published data due to the lack of information on other tumor markers, such as cytokeratin (CK) 5/6 expression, epidermal growth factor receptor (EGFR), and Ki67. We were therefore unable to precisely distinguish between basal-like and triple-negative tumors, or between luminal A and luminal B tumors. Finally, subject numbers in our subgroup analyses were limited.In conclusion, we found that current BMI and adult weight gain are associated with the risk of luminal and triple-negative breast cancer among postmenopausal women only. Our results provide additional evidence for these associations and suggest further etiological heterogeneity among tumor subtypes.Table S1. Associations between BMI and breast cancer risk by tumor. (XLS 40 KB)Additional file 1:


Sleep disturbance, a correlate of which is daytime napping, has been hypothesised to be associated with risk of breast and other cancers.We estimated relative risks (RR) of breast and other invasive cancers by the reported frequency of daytime napping in a large prospective cohort of middle-aged women in the UK.vs rarely/never) was associated with slightly increased risks of breast cancer  and of other cancers , but the RRs decreased significantly with increasing follow-up time . Four or more years after baseline, there was no elevated risk of breast cancer , and only marginally greater risk of other cancers .During an average of 7.4 years of follow-up, 20 058 breast cancers and 31 856 other cancers were diagnosed. Over the first 4 years of follow-up, daytime napping (sometimes/usually The effect of pre-clinical disease is a likely explanation for the short-term increased risk of breast and other cancers associated with daytime napping. Concern about possible increased risks for cancer associated with night work, circadian rhythm disruption, and impaired nocturnal melatonin production . This isThe Million Women Study, a population-based prospective cohort study, has been described in detail elsewhere . Brieflyhttp://www.millionwomenstudy.org) with questions on a range of health and lifestyle factors, including: ‘Do you have a nap during the day?’, with possible responses ‘rarely/never’, ‘sometimes’, and ‘usually’. Data on incident cancers during the follow-up period, coded according to the International Classification of Diseases, 10th Revision , with possible responses ‘rarely/never’, ‘sometimes’, ‘usually’, and ‘most of the time’ the latter two responses were combined to assess agreement with baseline data. Baseline and repeat responses were compared using Cohen’s kappa statistic for agreement  and SpeaRelative risks (RR) were estimated by categories of daytime napping at baseline using Cox regression, with minimal adjustment by stratification for age at and region of recruitment, and further adjustment for health and lifestyle covariates, as described below. Analyses were conducted either over the full period of follow-up for incident cancer, or, to investigate napping as a possible marker of pre-clinical disease, after dividing follow-up time from baseline into approximately equal intervals . Tests for trends in RRs with increasing follow-up time were conducted by inverse-variance weighted least squares regression of the log RRs against the average time at risk in each 2-year follow-up period. All statistical tests were two-sided. All analyses were performed using the Stata version 12.0 .In total, 795 238 women aged 50–64 years at recruitment were included in these analyses, with 7.4 years of follow-up per women on average . During After exploring effects of potential confounders, we adopted a multivariable model for subsequent analyses of RRs in relation to daytime napping at baseline, adjusting for age at recruitment, region of residence, smoking status, body mass index, sleep duration, use of menopausal hormone therapy, socioeconomic status, strenuous physical activity, and alcohol consumption  for napping sometimes and 1.11 (1.07–1.15) for napping usually ly/never .vs those who reported napping rarely or never, in each 2-year period of follow-up after baseline (P=0.001 for trend) and for other cancers (P=0.01 for trend). The RR of breast cancer was highest in the first 4 years of follow-up , but after 4 or more years of follow-up (average 7.6 years), there was no significant excess risk associated with more frequent napping . A similar pattern was observed in the RRs for invasive cancers other than breast cancer . In detailed investigations by cancer site, associations during the first 4 years after baseline were attenuated 4 or more years after baseline, despite similar case numbers in each period, and became nonsignificant for all sites except the lung and endometrium (We also estimated RRs for the dichotomous comparison of women who reported napping either sometimes or usually baseline . Resultsometrium . Becauseometrium , we alsoPre-clinical disease is a likely explanation for the observed decline over time in the risk of cancer associated with daytime napping. Because good repeatability of self-reported napping behaviour was maintained over time, regression dilution due to reporting errors or changes in napping behaviours would not be expected to produce the observed attenuations of RRs during follow-up. It is unknown whether associations of cancer risk with other sleep or fatigue-related behaviours might also reflect pre-clinical disease.The main strengths of this study are its large size and prospective design, the virtually complete follow-up for incident cancers, and the ability to examine the repeatability of reported daytime napping several years later. For cancers other than breast cancer, however, follow-up may not be long enough to rule out a residual effect of pre-clinical disease, because some cancers present with specific symptoms later than others. It is also impossible to rule out residual confounding in reported RRs, and in particular we were unable to investigate potential confounding factors related to sleep or napping behaviours, such as chronotype and employment in shift work.In summary, there was an association between more frequent daytime napping and a slight increased risk of breast and some other cancers in the first 4 years of follow-up in this cohort. This is consistent with napping being a marker of pre-clinical disease in some women.


The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. The field of cancer prevention was formalized in the 1970s and coincided with the recognition that most cancers develop through a multi-step process with long latency . Breast Conceptually, there are multiple strategies for breast cancer prevention. Primary prevention is focused on blocking tumor cell initiation by minimizing carcinogen exposure or enhancing detoxification. Examples include avoiding the use of ionizing radiation on developing breast tissue, limiting exogenous estrogen exposure, and supplementation with dietary agents such as the cruciferous isothiocyanates, which activate the p450 carcinogen metabolism pathway . UnfortuBreast cancer was the first malignancy where targeted drug treatment trials in the adjuvant setting demonstrated a concomitant secondary prevention benefit for subsequent contralateral disease. An average 50% reduction in new primary breast cancers was identified among women treated for 5 years with the SERM, tamoxifen . More reGiven the clinical success of anti-hormone based chemoprevention, it is surprising that of the more than 2 million high-risk women in the US alone, the number of women using tamoxifen for prevention is declining, with reports of 120,000 in 2000 to 20,500 in 2010 . SimilarThe toxicity profile and therapeutic index of SERM therapy is a clearly identified detractor to the drug’s acceptance among women ,7. When An additional limitation to women embracing breast cancer chemoprevention strategies is that many women may not be informed of their increased risk and thus do not know they are candidates for preventive strategies. While several models are currently utilized to predict a woman’s breast cancer risk and guide indication for chemoprevention, a comprehensive model that incorporates all known risk factors does not exist. The Breast Cancer Risk Assessment Tool (BCRAT), also known as the GAIL model, is commonly used to define high-risk women by predicting 5-year and lifetime breast cancer risks. To predict breast cancer risk, the GAIL model uses current age, age at menarche, age at first birth, number of first degree relatives with breast cancer, number of previous breast biopsies, and any pre-malignant histology results, with age being the most heavily weighted factor . Anotherneu positive and triple negative breast cancer subtypes remains unmet.Finally, an additional limitation of endocrine based chemoprevention agents is their selection against only ER positive breast cancers. Thus, SERM therapy is predicted to prevent only 38% of breast cancers during the time of treatment and would, therefore, be ineffective for the majority of women . The neeThe ideal chemoprevention agent would be highly effective at eliminating breast cancer with few off-target effects, required for a limited duration of time, and inexpensive. The SERMs meet each of these ideals only partially, as discussed above. None-the-less, tamoxifen is a success story for chemoprevention when compared to other agents tested against lung and prostate cancer, and important lessons learned from these studies need to guide further prevention research. For example, data from epidemiological and preclinical animal-model studies suggest that there are key components of the diet that are cancer-protective. These data led to a number of vitamin-based intervention trials, where, unfortunately, the results were not as expected. For example, not only did vitamin E fail to decrease risk of prostate cancer in high-risk men , and vitObservational studies have addressed the potential for use of non-steroidal anti-inflammatory drugs (NSAIDs) as breast cancer preventive agents, with mixed results. In prospective outcome studies, use of the non-selective COX-2 inhibitors aspirin and ibuprofen was associated with decreased recurrence and breast cancer related death ,18. HoweIn addition to the NSAID observational studies, evidence is increasing that COX-2 is causally involved in early stage breast cancer and thus a viable target for prevention. Thea Tlsty and colleagues have studied COX-2 expression in early malignant human tissues and shown that ductal carcinoma in situ (DCIS) lesions, along with normal breast epithelium adjacent to DCIS, express high levels of COX-2. In their cohort, expression was highest in the normal tissue adjacent to DCIS, implicating the upregulation of COX-2 in the very earliest stages of transformation . FurtherBased on experience gained to date, it is clear that several barriers significantly reduce both the feasibility of breast cancer prevention and patient confidence in these strategies. As described above, barriers include the inability to accurately predict at the individual level an impending or future breast cancer, the need to understand when in a woman’s life to implement the intervention, uncertainties regarding optimal duration of treatment, and negative side effects associated with current drugs. None-the-less, the unique biology of the mammary gland will likely permit the resolution of many of these barriers, making breast cancer prevention a viable objective. Not only does the majority of mammary gland development occur postnatally, but terminal differentiation is conditional and developmentally plastic. While these features may contribute to the high susceptibility of the breast to transformation, these feature have also permitted the identification of lifecycle-specific windows of breast cancer risk that may be amenable to therapeutic interventions .The unique biology of the breast begins in utero with breast ductal anlagen development . After bPivotal epidemiologic studies established that lifecycle events predict breast cancer risk, including age at puberty, the number of menstrual cycles across a lifetime, age at first birth, multiparity, and age at menopause ,39. Impoincrease in risk for breast cancer that occurs after each childbirth, regardless of the woman’s age [Multiple, large population studies demonstrate a transient an’s age –45. Albran’s age . Data shan’s age ,45. Furtan’s age ,46–48.To prevent the incidence of postpartum breast cancer, we must first understand how this unique life window promotes breast cancer. While pregnancy hormones are obvious candidates, the postpartum window also includes the unique process of mammary gland involution, which contributes to breast cancer progression in rodent models . During The identification of the mechanisms by which the postpartum involuting breast may promote breast cancer has opened the potential for specific chemoprevention strategies that target this at-risk population. The increase in COX-2 expression during involution provides support for targeting the COX-2 pathway and proof of concept was shown using a preclinical model of postpartum breast cancer. In this model, inhibition of COX-2, via NSAID administration during the two week period of murine postpartum involution, reduced mammary gland collagen deposition, decreased tumor COX-2 expression, and blocked tumor cell growth and invasion . ImportaAge related involution that occurs with menopause has been identified as marker of breast cancer risk; however the mechanism remains unknown . MenopauMenopause is a difficult time period to study in women due to the inability to readily identify its onset combined with wide inter-individual variation in the length of time (2–5 years) in which this process occurs. The use of pre-clinical models, however, has allowed researchers to study the impact of loss of ovarian function on breast cancer. The most commonly used model of menopause is surgical ovariectomy (OVX). Similar to humans, obesity has little effect on mammary tumor incidence in rodents prior to OVX . In contGiven that an impaired metabolic response to OVX-induced weight gain appears critical to the emergence of obesity-associated tumor promotion, the window of menopausal weight gain may provide a narrowed window during which interventions that improve metabolic control could be used to target mammary tumor growth. Metformin, a commonly prescribed anti-diabetic drug, is known to improve metabolic control. When administered to obese tumor-bearing rats during the period of OVX-induced weight gain, metformin significantly decreased tumor burden after 4 weeks . ImportaDevelopment of the mammary gland occurs in discrete and identifiable lifecycle windows that coincide with ‘hot-spots’ for breast cancer risk. These developmental windows are characterized by stromal–epithelial interactions that likely drive cancer progression. Postpartum breast involution and peri-menopause represent two lifecycle windows that are highly amenable to intervention. While additional studies are certainly necessary to confirm these approaches, current data suggest that targeting these ‘tissue-remodeling’ windows could provide the opportunity to increase treatment efficacy while decreasing the negative side effects associated with long term treatments, thereby improving effectiveness and patient acceptance of breast cancer prevention strategies.


The high breast cancer mortality rate in Sub-Saharan Africa has been attributed to a lack of public awareness of the disease which often leads to late diagnosis of the disease. Little is known about the level of knowledge and awareness of breast cancer in Angola. Previous studies have shown that breast cancer awareness is higher among well-educated people. The goal of this study was to assess breast cancer knowledge and awareness among university students in Angola.We conducted a cross-sectional survey of university students using a self-administered questionnaire to investigate participants’ awareness and knowledge of breast cancer. A total of 595 university students in medical and non-medical programs successfully completed the survey.Our results showed insufficient knowledge of breast cancer among university students in Angola irrespective of whether they were in medical or non-medical programs. The majority of the participants were not aware of some of the early signs of breast cancer such as change in color or shape of the nipple, even though they appreciated the need for monthly breast self-examination. Overall most of the participants indicated the need for increased breast cancer awareness among university students.The study points to the insufficient knowledge of university students in Angola about breast cancer. We expect that our results may provide useful data that may be used by the department of health in Angola and other African countries to formulate health education programs aimed at increasing awareness and promote screening and early detection of breast cancer in the continent. Breast cancer is the most common type of cancer in women worldwide. There has been a significant increase in the incidence of breast carcinoma in sub-Saharan African countries and in other low-resource countries , 2. In cWhile in Western countries, breast cancer screening is usually done using mammograms, the use of mammograms is limited and inaccessible to most women in sub-Saharan Africa. This situation is unlikely to change in the foreseeable future . In the Awareness and understanding of breast cancer in Africa is generally low. In recent years, the World Health Organization and several international organizations such as The Breast Health Global Initiative (BHGI) have sought to increase breast cancer awareness among African women , 17. StuThis study was designed to evaluate the level of breast cancer awareness among university students in Angola. In particular, we focused on perceptions about the causes of breast cancer, risk factors associated with breast cancer and knowledge of breast self-examination. Participants were drawn from students enrolled in Medical and Health related programs and non-medical programs from six universities in the capital Luanda. Permission to conduct the study was sought and granted by the University of Metodista de Angola's Review Board. At participating institutions, the purpose of the study was explained to participants and those who freely agreed to participate were enrolled in this study. A total of 595 students  volunteered and successfully completed the survey. Participants in non-medical programs were drawn from a teacher-training, foreign language and biological science programs.We used a modified version of the Breast Cancer Perceptions and Knowledge Survey previously used by Powe et al . The queWe adapted items for use in this study by including the response, “I don't know” in addition to the yes (agree)-no (disagree) format used by Powe et al  on the sA demographic section of the questionnaire was used to acquire participants’ information such as gender, age, high school attended, marital status, current academic class, and knowledge of someone with breast cancer. Based on previous studies , we hypoData were analyzed using Statistical Package for the Social Sciences . Descriptive statistics with cross-tabulations were performed and frequencies were generated for correct and incorrect answers for all items. As previously stated, the knowledge indices were calculated for each student by summing the number of correct answers. Participants were grouped depending on whether they were in a medical program or non-medical program. Pearson Chi-Square test was used to examine the association between variables, with significance level set at pThis study assessed breast cancer knowledge and awareness among university students in Angola . We partOur results showed a widespread lack of knowledge on risk factors associated with breast cancer. Participants who reported knowledge of someone with breast cancer were slightly more knowledge than those who did not. All the other variables such as age, gender, academic level, high school attended and marital status did not have a significant influence on level of understanding of risk factors. Additionally, no differences (p<0.05) were observed between students in non-medical programs and those in medical programs. As shown in Our results showed that 69.4% and 72.4% of medical and non-medical students respectively reported having knowledge of BSE. However, it was interesting to note that only 40.2% of female medical students and 38.7% non-medical female students reported that they could confidently perform BSE. Given that a majority of the students (more than 60%) where not aware that a change in the color or shape of the nipple could be a sign of breast cancer and more than 50% did not know the best time to perform BSE , it remaOverall, our study is in agreement with previous studies done in other parts of the world and showed the general lack of adequate knowledge on breast cancer by university students in Angola. The overall mean score for Medical students was 9.9 ± 0.25 (mean ± SEM) and for non-medical students, 9.4 ± 0.21(mean ± SEM) out of a total possible score of 25. The only variable that had a significant effect on breast cancer awareness was knowledge of someone with breast cancer, with participants who knew someone with breast cancer being significantly more knowledgeable (p<0.05) than those who indicated that they did not know anyone with breast cancer. Other variables such as gender, age, marital status, and high school attended did not have a significant influence on level of knowledge. Interestingly, most of the participants  indicated the need for more information on breast cancer to be provided in high school and university, thus, suggesting a willingness to learn more about the disease.Breast cancer mortality rate is much higher among Sub-Saharan women as compared to women in Western countries, even though the incidence rate is much higher in Western women , 2. AparIn contrast to a study done by Mafuvadze et al  who repoA majority (80%) of participants in this study shared the view that lumps in the breast that are cancerous would be painful. This, as reported by Powe et al , is a wiThe majority of students in this study showed a general lack of understanding of some of the common risk factors associated with breast cancer. Although some of these risk factors are not easily modifiable, others, such as the use of oral contraceptives and hormone replacement therapy (HRT), alcohol consumption, and physical inactivity can be altered in order to reduce risk. In this study, more than 60% of students were not aware of the risk associated with use of oral contraceptive and hormone replacement therapy. University students are at a stage where they are making important reproductive decisions such as use of oral contraceptives. They should, therefore, be aware of the risk associated with long term use of oral contraceptives. Though use of hormone replacement therapy is not common in Africa at present, it is, however, likely that a significant number of women will have access to it as African economies develop. Though a significantly high number (60%) of students were aware of the fact that having children early might reduce the risk of breast cancer, less than 8% were aware of the benefit of long term breastfeeding in reducing breast cancer risk. Studies in other parts of the world reportedly showed that well-educated and higher socio-economic status level women were more likely to formula feed than breast-feed –33. In aThere is not much information on breast cancer awareness among men in Africa. Men tend to view breast cancer as a female only disease as revealed in a study by Thomas  where meIn Angola, like in many Sub-Saharan countries, there is a general unwillingness to openly discuss issue pertaining to reproductive health . Howeveret cetera may lead to increased awareness. For example, recently, in Zimbabwe programs were begun in which trained hairdressers distribute and disseminate information on reproductive health [While a lot of attention in Sub-Saharan Africa has been on HIV and AIDS in the last three decades, it is important to also focus on other important disease like breast and cervical cancers which continue to cause high mortality among women . Health e health . In addie health , breast Our results showed a general lack of knowledge of breast cancer among university students in Angola irrespective of whether they were in medical programs  or non-medical programs. We contend that these findings further highlight the need for developing and implementing effective breast cancer education and prevention programs among university and the general public in Angola. We expect that our results may provide useful data that may be used by health institutions in Angola and other African countries to formulate health education programs focusing on breast cancer that targets university students.We think that the apparent lack of breast cancer awareness and knowledge among university students in this study is further evidence for widespread ignorance among the general public. University students tend to be better informed on health issues than the average public person . It is, Facebook and Twitter in Africa. There is a lot of potential to exploit these online social media as a means of disseminating information on breast cancer.Establishment of trained breast cancer awareness peer groups at universities and other educational institutions in line with those currently promoting HIV awareness would likely increase breast cancer awareness. The last few years have seen widespread use of internet social media such as


Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 . Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012).Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the informed consent process. There is some evidence that antidepressant (AD) use is associated with increased cancer risk Experimental studies have demonstrated that some ADs promote tumor growth in animals The results of epidemiological studies examining an association between AD use and breast cancer A growing area of concern in the biomedical sciences, including oncology, is the potential for financial conflict of interest to influence the outcome of a study A list of FDA approved antidepressants was generated and a search was conducted for English language articles in MEDLINE (via ISI Web of Knowledge), PSYCINFO, Science Citations Index, and the Cochrane Database of Controlled Trials Register (no year limits through November 2010). Following Lawlor et al. The main criteria for study selection were 1) clinical studies  that assessed the relationship between AD use and breast and ovarian cancer and 2) preclinical studies that that assessed the carcinogenic properties of ADs on tumor lines or in animals. Carcinogenic was defined as “mutagenetic,” “clastogenetic,” “epigenetic,” “mitogenetic,” “cytogenetic,” “genotoxic,” “tumorigenic,” neoplastic, “anti-apoptotic,” “teratogenetic,” “associated with sister chromatid exchanges,” and “induction of genomic instability.” We excluded studies that examined medications other than ADs , and human studies that did not empirically assess the relationship between ADs and breast and ovarian cancer . We also excluded epidemiological studies that assessed the relationship between AD use and other cancer types (e.g. lung) as they were beyond the scope of this review.Electronic database searches, reference mining and consultation with an expert in the field yielded 4,343 citations. Although our search identified 2,106 clinical trials in the Cochrane Central Register of Controlled Trials, no randomized or quasi randomized controlled trials were found to have breast or ovarian cancer as any outcome measure. After removing duplicates, 4,120 were excluded based on the title or abstract review (using the study selection criteria described above), 184 records were requested and 183 (99.5%) were retrieved and reviewed. Of the retrieved records, 122 were rejected because they did not meet study inclusion criteria . Studies that assessed the inter-relationship among serotonin, SSRIs, certain TCAs, prolactin, and tamoxifen, and how these inter-relationships affect pharmacodynamics and cancer risk, were retrieved and underwent a preliminary review. The remaining articles (N = 61) underwent full review .Any concerns regarding eligibility were discussed and agreed upon by the investigators. For the 61 articles that met our study criteria, one investigator (LC) originally abstracted data about the relationship between ADs and cancer and another  independently reviewed the data. Abstraction of the data took place prior to screening for industry associations and reviewers were blinded with regard to knowledge about the researchers' industry associations. Because a main objective of the present study was to identify the original researchers' stated conclusions regarding breast and ovarian cancer risk and ADs,  there was little ambiguity in terms of how to abstract the data. There was one discrepancy which was resolved by consultation with an outside expert who was blinded to knowledge about industry associations.Twenty–six epidemiological studies were reviewed Thirty-five pre-clinical  studies were reviewed We were also interested in discerning whether there was a connection between industry ties and qualitative conclusions about cancer risk and AD use. Using multimodal screening techniques, we examined the relationship between principal investigators' conclusions and their financial ties to the pharmaceutical industry. The multi-modal screening methods applied included: MEDLINE, , and the following internet search engines: Lexis-Nexis, the U.S. Patent and Trademark Office internet site on patents awarded, and the internet site for SEC filings. The development of both criteria for “holding a financial interest” and for parameters regarding the timing of financial associations (5 years before and five years after a study was published) were based on standards set by government bodies, journals, and professional societies as well as based on prior publications Over one-third (38.4% or 10/26) of the epidemiological studies reported statistically significant findings, of which 8 were case-control studies and 2 cohort studies. Almost one-third (28.6% or 10/35) of the pre-clinical studies reported a positive finding with regard to the AD agent being carcinogenic, a tumor promoter, or genotoxic. Thus, 32.8% (20/61) of the epidemiological and pre-clinical studies reported an association between ADs and cancer . There wThe pooled odds ratio of 1.11 , suggests that ADs may be associated with a small increase in breast and ovarian cancer risk see . When weNone of the 4 epidemiological studies for which the principal investigator (PI) had industry ties reported a positive association between AD use and cancer risk. Of the 22 studies for which the PI had no industry ties, 45% (10/22) reported positive findings. Likewise, none of the 11 pre-clinical studies for which the PI had industry ties reported positive cancer findings. Of the 24 studies for which the PI had no industry ties, 42% (10/24) reported that ADs were carcinogenic, tumor promoters, genotoxic, or neoplastic. Thus, in total, none of the 15 researchers who had industry ties reported positive cancer findings, compared with 43% of the researchers without industry ties. There was a statistically significant relationship between researchers' industry ties and conclusions regarding ADs and cancer (2-sided Fisher's Exact test P = 0.0012).The meta-analysis of epidemiological studies suggests there may be a modest increase in the risk of breast/ovarian cancer with the use of ADs, especially SSRIs. Other potential explanatory factors for this finding include the role of depression itself rather than treatment with AD generic risk whether or not it has (emphasis added)” The fact that industry affiliations were significantly associated with negative findings regarding cancer risk raises public health and policy issues because there is increasing evidence that financial ties among industry, investigators, and academic institutions can affect the research process Moreover, there are many posited mechanisms for the link between conclusions and industry ties—mechanisms that can be subtle and unintentional. Our current regulatory system does not incentivize industry to develop maximally informative study designs Given the lack of epidemiological data on low-dose SSRI use, the issue of informed consent becomes a complex and critical one. It is likely that women, especially women being prescribed adjunctive AD therapy for depression secondary to a breast or ovarian cancer diagnosis or as adjunctive therapy for pain and hot flashes, would want to know about the positive cancer findings of animal and human studies, the genotoxic properties of some ADs, as well as the potential neoplastic/antiproliferative findings reported in some studies. Additionally, our findings have implications in light of the latest U.S. Preventive Services Task Force (USPSTF) guidelines recommending that women between the ages of 40–49 do not need routine screening for breast cancer de-minimis figures. Second, although we searched multiple databases, we did not search EMBASE. However, in light of the documented retrieval congruence between MEDLINE and EMBASE Our study has several limitations. First, some of the articles retrieved were published prior to the development of COI policies and standard disclosure practices. It is likely that our screening techniques missed some industry ties and disclosure depends upon honest reporting of those ties. Thus, our findings should be considered Text S1Search strategy.(DOC)Click here for additional data file.Table S1Summary of epidemiological studies on antidepressants and cancer risk.(DOC)Click here for additional data file.Table S2Results and study design of epidemiological studies.(DOC)Click here for additional data file.Table S3Summary of pre-clinical studies on antidepressants and cancer risk.(DOC)Click here for additional data file.Table S4Results regarding carcinogenicity from pre-clinical studies.(DOC)Click here for additional data file.


Vitamins are important in various biochemical and physiological processes and are essential for the normal functioning of our bodies. Several studies suggested the role of vitamins A, E and D in carcinogenesis.The aim of this study was to analyze an association between concentration of vitamins A, E and D in serum and cancer risk in BRCA1 mutation carriers.Study was conducted on 99 patients affected by breast cancer and 198 healthy women matched to the cases by year of birth, adnexectomy, smoking and cancer family history. All cases and controls were carriers of Polish BRCA1 founder mutation .The concentration of vitamins A, E and D was quantitatively measured by HPLC chromatography . The mean levels of analyzed vitamins were compared for cases and controls. For cancer risk assessment, individuals were divided into quartiles, based on the distribution of tested vitamin’s levels.Neither vitamin D, nor vitamin E were significantly associated with the disease risk. However, we found significant association of vitamin A concentration with cancer risk. Individuals in the quartile with the lowest concentration had the highest risk of breast or ovarian cancer.


An association of cigarette smoking with breast cancer risk has been hypothesized. However, results from previous studies have been inconsistent. This case-control study investigated the association of cigarette smoking with breast cancer risk in terms of estrogen-receptor/progesterone-receptor (ER/PgR) status. From among female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2011, 1,263 breast cancer cases  and 3,160 controls were selected. History of smoking , some smoking-related measures, and passive smoking from husbands  were assessed using a self-administered questionnaire. Polytomous logistic regression and tests for heterogeneity across ER+/PgR + and ER-/PgR- were conducted. For any hormone receptor subtype, no significant association was observed between history of smoking  and breast cancer risk. Analysis of smoking-related measures revealed that starting to smoke at an early age of ≤19 years was significantly associated with an increased risk of postmenopausal ER-/PgR- cancer . Other measures of smoking such as the number of cigarettes per day, the duration of smoking, and start of smoking before the first birth were not associated with breast cancer risk for any receptor subtype. There was no association between passive smoking  and breast cancer risk for any of the four subtypes. These results indicate that history of smoking and passive smoking from husbands may have no overall effect on breast cancer risk for any hormone receptor subtype. However, it is possible that women who start to smoke as teenagers may have a higher risk of developing postmenopausal ER-/PgR- cancer. Further studies are needed to clarify the association of smoking with breast cancer risk, especially the role of starting to smoke at an early age. Breast cancer is one of the most common cancers worldwide  status, i.e., ER+/PgR+, ER+/PgR-, ER-/PgR+, and ER-/PgR-.In January 1997, we began a questionnaire survey in connection with the present study. Information on lifestyle and personal history was collected from all patients at their first admission to the Miyagi Cancer Center Hospital (MCCH), using a self-administered questionnaire. The questionnaire was distributed to patients on the day of their reservation for initial admission, i.e., 10-15 days before admission, and collected by nurses on the day of actual admission. The purpose of the survey was stated on the cover page of the questionnaire. We considered the return of self-administered questionnaires signed by the patients to imply their consent to participate in the study.The MCCH is located in the southern part of Miyagi Prefecture, and functions as a hospital for both cancer and benign diseases. Details of the questionnaire survey have already been described elsewhere  use and exogenous female hormone use. Items related to the referral status and area of residence were also included. Between January 1997 and December 2011, the questionnaire was distributed to 26,984 first-admitted patients, of whom 24,062 responded.Cases and controls were selected from among 24,062 patients who responded to the questionnaire survey. To identify incident cases of female breast cancer, a list of the patients was linked with both the hospital-based cancer registry file and the disease registration database at MCCH. The cancer registry records all cancer cases confirmed by clinical, cytological and/or histopathological examination at the MCCH. Through the linkage, 24,062 patients were classified into 2,219 with a past history of cancer, 7,707 males with cancer, 1,309 females with breast cancer, 4,779 females with other cancers, and 8,048 non-cancer patients . Among the 1,309 females with breast cancer, 1,302 aged 30 years and over were included as the study cases.Controls were selected from among female non-cancer patients without history of cancer . Patients with benign tumors have been classified as non-cancer patients for the present study. After excluding patients under 30 years, 3,587 female non-cancer patients aged 30 years and over were selected as possible controls, from whom 295 subjects with smoking-related disease were excluded. Finally, a total of 3,292 female non-cancer patients were included as controls. Smoking-related diseases were defined based on the procedure used in our previous studies , age at the start of smoking , whether smoking had started before the first birth , duration of smoking , the mean number of cigarettes smoked per day during the smoking period , and the number of pack-years of smoking . Subjects who quit smoking within one year before the present admission were regarded as current smokers. Pack-years of smoking were calculated by multiplying the duration of smoking by the mean number of cigarettes smoked per day divided by 20. Whether smoking had started before the first birth was defined by comparing the age at the start of smoking and the age at first birth. When age at the start of smoking was equal to the age at first birth, the case was assigned to the “uncertain” category. Cut-off points for age at the start of smoking were determined arbitrarily, considering the importance of the category for subjects who started smoking as teenagers. For the other three exposure variables, the mid-point among the controls was used as a cut-off point. Subjects for whom data on smoking history were missing [n = 39 (3.0%) for cases and n = 132 (4.0%) for controls] were excluded from the subsequent analysis, leaving 1,263 cases and 3,160 controls.The only exposure variable related to passive smoking was the husband’s smoking status . This information was obtained from married subjects. The risk for passive smoking was investigated only among never-smokers.Information on the expression of ER and PgR in breast cancers was extracted from medical records. To measure ER/PgR status, enzyme immunoassay (EIA) had been used in the early period of the study to determine hormone receptor status. After mid-2003, immunohistochemistry (IHC) assay was routinely conducted. The concordance between the two assays was 94.3% for ER and 100% for PgR in the laboratory of the MCCH  and 95% confidence intervals (CIs) were calculated for each category.We considered the following variables to be potential confounders: age, year of recruitment, referral status , area of residence , alcohol drinking , occupation , age at menarche, age at menopause, menopausal status , reason for menopause , parity number, age at first birth, family history of breast cancer in mother or sisters , physical activity , body mass index (BMI), and history of use of exogenous female hormones or OCs . Occupation classification was based on the categorization used in our previous study .Dose-response relationships were tested by treating each exposure category as a continuous variable. We conducted Wald tests for heterogeneity of breast cancer risk across ER+/PgR + and ER-/PgR-. Values were regarded as significant if the two-sided The baseline characteristics of the study subjects are presented in Table Table Table Ptrend = 0.71). No other exposure variables were associated with breast cancer risk for either of the hormone receptor subtypes.Table Tables This hospital-based case-control study was designed to investigate the association between smoking and breast cancer risk in relation to joint hormone receptor status. The risks for history of smoking  and various smoking-related measures, including age at the start of smoking, whether an individual started smoking before her first birth, the number of cigarettes smoked per day, the duration of smoking, and the number of pack-years, and passive smoking from husbands  were evaluated, and analysis based on menopausal status was also performed. Evidence for smoking-related breast cancer risk in relation to hormone receptor subtype has been limited in both Japan and Western countries  had no overall effect on breast cancer risk for any hormone receptor subtype. However, a few smoking-related measures were associated with the risk of ER-/PgR- cancer: the analysis for all subjects showed that having started to smoke at an early age of ≤19 years was associated with an increased risk of ER-/PgR- cancer, although this did not reach statistically significance. According to menopausal status, starting to smoke at an early age of ≤19 years was significantly associated with an increased risk of postmenopausal ER-/PgR- cancer, although there was no linear relationship between age at the start of smoking and the risk of ER-/PgR- cancer. On other hand, no smoking-related measure was found to be associated with the risk of ER+/PgR + cancer in either pre- or postmenopausal women. Although the significant association of an early age at the start of smoking with the risk of postmenopausal ER-/PgR- cancer must be interpreted carefully because of the wide confidence interval, this finding suggests that early exposure to tobacco smoke may stimulate the development of ER-/PgR- cancer. Cell-proliferative activity in the breast is known to be very high during the teenage period  was comparable to that in the general population of Miyagi Prefecture (20.5%)  and breast cancer risk for any hormone receptor subtype. There was also no association between passive smoking  from husbands and the risk of breast cancer. However, detailed analysis of smoking-related measures showed that an early age at the start of smoking of ≤19 years was significantly associated with an increased risk of postmenopausal ER-/PgR- cancer, suggesting that early exposure to tobacco smoke may stimulate the development of ER-/PgR- cancer. Other smoking-related measures such as the number of cigarettes smoked per day, the duration of smoking, and the number of pack-years were not associated with breast cancer risk for any hormone receptor subtype. Cigarette smoking, which may be a preventable risk factor, has complicated effects including direct carcinogenic and antiestrogenic effects. Further studies including bigger, pooled cohort studies are required to clarify the association of smoking with breast cancer risk.