The risk of cardiovascular disease following breast cancer by Framingham risk score

Objectives

This study evaluates the risk of cardiovascular disease (CVD) following breast cancer, accounting for baseline CVD risk.

Methods

Within the EPIC-NL (Dutch part of the European Prospective Investigation into Nutrition and Cancer) cohort, 1103 women were diagnosed with breast cancer. For every breast cancer patient, 3–4 women without breast cancer (n = 4328) were selected matched for age, year, and time since cohort enrollment. Based on CVD risk factors at cohort enrollment, 10-year risk of CVD was calculated and categorized: low (< 10%), intermediate (10–20%), high (> 20%). Cox proportional hazard models assessed the risk of CVD events (hospitalization or mortality) and CVD mortality of women with versus without breast cancer, adjusted for baseline CVD risk.

Results

After median follow-up of 5 and 6 years, 92 (8.3%) and 325 (7.5%) CVD events occurred in women with and without breast cancer, respectively. In the low CVD risk group, women with breast cancer had 1.44 (95% CI 1.00–2.06) times higher risk of CVD events than women without breast cancer. In the intermediate and high CVD risk categories, risk of CVD events was similar in women with and without breast cancer. Overall, women with breast cancer had 1.77 (95% CI 1.10–2.86) times higher risk of CVD mortality than women without breast cancer.

Conclusions

Among women with low CVD risk, women with breast cancer have a higher risk of CVD event than women without breast cancer. Overall, women with breast cancer have a higher risk of CVD mortality than women without breast cancer.

     

A polygenic risk score for breast cancer risk in a Taiwanese population

Background

Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population.

Methods

In total, 446 breast cancer patients and 514 healthy controls were recruited for this case–control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC).

Results

Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose–response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51–3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%.

Conclusions

Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.

     

Benign breast disease and risk of thyroid cancer

Background

It has been suggested that breast and thyroid diseases may be linked. The aim of this study was to investigate the association between benign breast disease and subsequent risk of thyroid cancer.

Methods

Postmenopausal women (n = 133,875) aged 50–79 years were followed up for a mean of 14 years. Benign breast disease was defined by history of biopsy. Incident thyroid cancer cases were confirmed by medical record review. Multivariable Cox proportional hazard modeling was used to estimate hazard ratios.

Results

There were 370 incident thyroid cancer cases during the follow-up period. Compared to women without BBD, women with BBD had a significant increased risk of thyroid cancer after adjusting for potential confounders (HR 1.38 95% CI 1.10–1.73), especially for women with more than two biopsies (HR 1.59 95% CI 1.10–2.26). There were no significant differences in thyroid tumor size, stage or histologic types between women with and without BBD.

Conclusion

Our large prospective study observed that postmenopausal women with BBD had an increased risk for thyroid cancer compared with women without BBD. A more detailed investigation of thyroid cancer risk according to different subtypes of benign breast disease is needed to better understand the association observed between thyroid and benign breast diseases.

     

Active smoking and risk of Luminal and Basal-like breast cancer subtypes in the Carolina Breast Cancer Study

Purpose

Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype.

Methods

Using population-based case–control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case–control odds ratios (OR) and 95 % confidence intervals (CI).

Results

Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92–1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69–1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19–1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57–1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null.

Conclusions

Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.

     

Adolescent diet and risk of breast cancer

Background

Early life exposures, including diet, have been implicated in the etiology of breast cancer.

Methods

A nested case-control study was conducted among participants in the Nurses' Health Study who completed a 24-item questionnaire about diet during high school. There were 843 eligible cases diagnosed between onset of study (1976) and before the return of the high school diet questionnaire (1986), who were matched 10:1 with controls on the basis of age.

Results

Women who had, during adolescence, a higher consumption of eggs, vegetable fat and fiber had a lower risk of breast cancer, whereas risk of breast cancer was increased among women who consumed more butter.

Conclusions

A possible association of elements of adolescent diet with risk of breast cancer is reported, but the findings require confirmation in prospective study.

     

Family history and risk of breast cancer: an analysis accounting for family structure

Purpose

Family history is an important risk factor for breast cancer incidence, but the parameters conventionally used to categorize it are based solely on numbers and/or ages of breast cancer cases in the family and take no account of the size and age-structure of the woman’s family.

Methods

Using data from the Generations Study, a cohort of over 113,000 women from the general UK population, we analyzed breast cancer risk in relation to first-degree family history using a family history score (FHS) that takes account of the expected number of family cases based on the family’s age-structure and national cancer incidence rates.

Results

Breast cancer risk increased significantly (P _trend < 0.0001) with greater FHS. There was a 3.5-fold (95% CI 2.56–4.79) range of risk between the lowest and highest FHS groups, whereas women who had two or more relatives with breast cancer, the strongest conventional familial risk factor, had a 2.5-fold (95% CI 1.83–3.47) increase in risk. Using likelihood ratio tests, the best model for determining breast cancer risk due to family history was that combining FHS and age of relative at diagnosis.

Conclusions

A family history score based on expected as well as observed breast cancers in a family can give greater risk discrimination on breast cancer incidence than conventional parameters based solely on cases in affected relatives. Our modeling suggests that a yet stronger predictor of risk might be a combination of this score and age at diagnosis in relatives.

     

Clinical and genetic characterization of hereditary breast cancer in a Chinese population

Background

Breast cancer develops as a result of multiple gene mutations in combination with environmental risk factors. Causative variants in genes such as BRCA1 and/or BRCA2 have been shown to account for hereditary nature of certain breast cancers. However,other genes, such as ATM, PALB2, BRIP1, CHEK, BARD1, while lower in frequency, may also increase breast cancer risk. There are few studies examining the role of these causative variants. Our study aimed to examine the clinical and genetic characterization of hereditary breast cancer in a Chinese population.

Methods

We tested a panel of 27 genes implicated in breast cancer risk in 240 participants using Next-Generation Sequencing. The prevalence of genetic causative variants was determined and the association between causative variants and clinico-pathological characteristics was analyzed.

Results

Causative variant rate was 19.2% in the breast cancer (case) group and 12.5% in the high-risk group. In the case group 2.5% of patients carried BRCA1 causative variant, 7.5% BRCA2 variants, 1.7% patients had MUTYH, CHEK or PALB2 variants, and 0.8% patients carried ATM, BARD1, NBN, RAD51C or TP53 variants. In the high-risk group 5.8% women carried MUTYH causative variants, 2.5% had causative variants in ATM, 1.7% patients had variants in BRCA2 and 0.8% in BARD1, BRIP1 or CDH1. There was no significant difference in the presence of causative variants among clinical stages of breast cancer, tumor size and lymph nodes status. However, eight of the 12 BRCA1/2 causative variants were found in the TNBC group.

Conclusions

We found increased genetic causative variants in the familial breast cancer group and in high-risk women with a family history of breast cancer. However, the variant MUTYH c.892-2A > G may not be directly associated with hereditary breast carcinoma.

     

Dietary fiber intake and risk of breast cancer defined by estrogen and progesterone receptor status: the Japan Public Health Center-based Prospective Study

Purpose

Epidemiological studies have suggested a protective effect of dietary fiber intake on breast cancer risk while the results have been inconsistent. Our study aimed to investigate the association between dietary fiber intake and breast cancer risk and to explore whether this association is modified by reproductive factors and hormone receptor status of the tumor.

Methods

A total of 44,444 women aged 45 to 74 years from the Japan Public Health Center-based Prospective Study were included in analyses. Dietary intake assessment was performed using a validated 138-item food frequency questionnaire (FFQ). Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence were calculated by multivariate Cox proportional hazards regression models.

Results

During 624,423 person-years of follow-up period, 681 breast cancer cases were identified. After adjusting for major confounders for breast cancer risk, inverse trends were observed but statistically non-significant. Extremely high intake of fiber was associated with decreased risk of breast cancer but this should be interpreted with caution due to limited statistical power. In stratified analyses by menopausal and hormone receptor status, null associations were observed except for ER-PR- status.

Conclusions

Our findings suggest that extreme high fiber intake may be associated with decreased risk of breast cancer but the level of dietary fiber intake among Japanese population might not be sufficient to examine the association between dietary fiber intake and breast cancer risk.

     

Assessment of potential risk factors for breast cancer in a population in Southern Brazil

Purpose

The aim of this study is to assess potential risk factors for breast cancer in a population in Southern Brazil and build a multivariate logistic model using these factors for breast cancer risk prediction.

Methods

A total of 4242 women between 40 and 69 years of age without a history of breast cancer were selected at primary healthcare facilities in Porto Alegre and submitted to mammographic screening. They were evaluated for potential risk factors.

Results

In all, 73 participants among the 4242 women had a breast cancer diagnosis during the follow-up of the project (10 years). The multivariate analysis considering all the patients aged 40–69 years showed that older age (OR 1.08, 95% CI 1.04–1.12), higher height (OR 1.04, 95% CI 1.01–1.09), and history of previous breast biopsy (OR 2.66, 95% CI 1.38–5.13) were associated with the development of breast cancer. Conversely, the number of pregnancies (OR 0.87, 95% CI 0.78–0.98) and use of hormone replacement therapy (OR 0.39, 95% CI 0.20–0.75) were considered a protective factor. Additionally, we performed an analysis separating the participants into groups of 40–49 and 50–69 years old, since a risk factor could have a specific behavior in these age groups. No additional risk factors were identified within these age brackets, and some factors lost statistical significance.

Conclusion

The risk prediction model indicates that the following variables should be assessed in this specific population: age, height, having had previous breast biopsies, number of pregnancies, and use of hormone replacement therapy. These findings may help to better understand the causal model of breast cancer in Southern Brazil.

     

Tree nut,peanut, and peanut butter intake and risk of postmenopausal breast cancer: The Netherlands Cohort Study

Purpose

Nut intake has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between nut intake and risk of postmenopausal breast cancer, and estrogen/progesterone receptor (ER/PR) subtypes.

Methods

In The Netherlands Cohort Study, 62,573 women aged 55–69 years provided information on dietary and lifestyle habits in 1986. After 20.3 years of follow-up, 2,321 incident breast cancer cases and 1,665 subcohort members were eligible for multivariate case-cohort analyses.

Results

Total nut intake was significantly inversely related to ER negative (ER??) breast cancer risk, with HR 0.55 (95% CI 0.33–0.93) for those consuming at least 10 g nuts/day versus non-consumers (p trend?=?0.025). There were no significant inverse associations with ER?+?or total breast cancer. While there was no variation between PR subtypes, the ER–PR- subtype was also significantly inversely associated with nut intake, with HR 0.53 (95% CI 0.29–0.99), p trend?=?0.037. Intake of peanuts and tree nuts separately was also inversely related to ER?? breast cancer subtypes, while no associations were found with peanut butter intake.

Conclusions

Our findings suggest an inverse association between nut intake and ER?? breast cancer, and no association with total or hormone receptor-positive subtypes.

     

<Emphasis Type="Italic">N</Emphasis>-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women

Background

Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia.

Methods

We conducted a case–control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype.

Results

In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38–3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype.

Conclusion

Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

     

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women’s Health Across the Nation

Purpose

Two case–control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer.

Methods

We evaluated this relationship in the longitudinal Study of Women’s Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment.

Results

Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77).

Conclusion

VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

     

A population-based audit of ethnicity and breast cancer risk in one general practice catchment area in North London,UK: implications for practice

Objectives

To conduct a pilot population-based study within a general practice catchment area to determine whether the incidence of breast cancer was increased in the Ashkenazi population.

Design

Population-based cohort study.

Setting

A single general practice catchment area in North London.

Participants

1947 women over the age of 16 who responded to a questionnaire about ethnicity and breast cancer.

Main outcome measures

Incidence of breast cancer, ethnicity.

Results

This study showed a 1.5-fold (95% CI 0.93–2.39) increase in breast cancer risk in the Ashkenazim compared with the non-Ashkenazi white population. The increased incidence was for both premenopausal and postmenopausal breast cancer (expected incidence pre:post is 1:4 whereas in the Ashkenazim it was 1:1; 51 and 52% of cases respectively). This increase was not shown in the Sephardim. Asians had a reduction in incidence (OR = 0.44; 95% CI 0.10–1.89). Results were adjusted for other risk factors for breast cancer.

Conclusion

This study showed a 1.5-fold increase in breast cancer rates in Ashkenazim compared with the non-Jewish white population when adjusted for age (i.e. corrections were made to allow comparison of age groups) and this is not observed in the Sephardic population. The proportion of premenopausal breast cancer was just over double that of the general population. This is the first general practice population-based study in the UK to address this issue and has implications for general practitioners who care for patients from the Ashkenazi community.

     

TP53 codon 72 polymorphism and breast cancer risk in Bangladeshi population

Background

Breast cancer, a hereditary or heterogeneous sporadic disease, is the most common cancer in women worldwide. The tumor suppressor TP53 gene has been found to be the most commonly mutated genes in many types of human cancers, including breast cancer. This study aimed to investigate the association of codon 72 polymorphism of TP53 gene with breast cancer risk in Bangladeshi females.

Methods

The study included 125 cases and 125 healthy controls. Genotyping and polymorphism were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis.

Results

The frequencies of the three genotypes Arg/Arg, Arg/Pro, and Pro/Pro were 43.2, 33.6, and 23.2% in cases, whereas 48.8, 40.8, and 10.4% in controls, respectively. The frequency of mutant homozygous (Pro/Pro) genotype was significantly increased in breast cancer patients as compared with controls (23.2 vs 10.4%), and showed 2.52-fold significantly increased risk for breast cancer (OR 2.5199, 95% CI 1.19–5.33, p = 0.0157). The frequencies of Pro/Pro genotype were significantly higher in breast cancer cases with non-breast feeding status. Pro allele frequency was found to be significantly increased in breast cancer cases (OR 1.4978, 95% CI 1.0357–2.1662, p = 0.0318).

Conclusions

Our data suggest that mutant (Pro/Pro) homozygosity at codon 72 of TP53 gene is significantly associated with breast cancer susceptibility in Bangladeshi women. In addition, this association was significantly related to lactating status.

     

Childhood and teenage physical activity and breast cancer risk

Purpose

Adult physical activity is associated with reduced breast cancer risk, but few studies have evaluated activity before adulthood. Early life may be an important period because of rapid breast development and hormonal changes. This study contributes new information by examining childhood (ages 5–12) and teenage (ages 13–19) activity separately and overall.

Methods

The Sister Study is a cohort of 50,884 women aged 35–74. Women reported age 5–19 sports/exercise activities and age 10 and 16 unstructured activities. Both hours and MET-hours of activity were considered in association with breast cancer overall, by ER status, and by menopausal status. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards models.

Results

2416 cases were diagnosed during follow-up (mean = 6.4 years). Participation in 7+ hours (vs <1 h) per week of sports/exercise during ages 5–19 was associated with reduced breast cancer risk (HR = 0.75; 95% CI 0.57–0.99). 7+ hours (vs <1 h) per week of unstructured physical activity at age 16, but not age 10, was inversely associated with breast cancer (HR = 0.81; 95% CI 0.70–0.95). Associations were more pronounced for ER+ tumors, especially for activity during the childhood (ages 5–12) period. Due to low correlation between childhood/teenage and adulthood activity in this study (r = 0.1), it is unlikely that recent activity explains our results.

Conclusions

Findings from this large cohort indicate higher levels of physical activity during ages 5–19 are inversely associated with breast cancer risk, supporting early life as a window of susceptibility for breast cancer development.

     

Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer: evidence from gene-based tests,single-marker regression,and whole-genome prediction

Purpose

Women diagnosed with breast cancer have heterogeneous survival outcomes that cannot be fully explained by known prognostic factors, and germline variation is a plausible but unconfirmed risk factor.

Methods

We used three approaches to test the hypothesis that germline variation drives some differences in survival: mortality loci identification, tumor aggressiveness loci identification, and whole-genome prediction. The 2954 study participants were women diagnosed with breast cancer before age 50, with a median follow-up of 15 years who were genotyped on an exome array. We first searched for loci in gene regions that were associated with all-cause mortality. We next searched for loci in gene regions associated with five histopathological characteristics related to tumor aggressiveness. Last, we also predicted 10-year all-cause mortality on a subset of 1903 participants (3,245,343 variants after imputation) using whole-genome prediction methods.

Results

No risk loci for mortality or tumor aggressiveness were identified. This null result persisted when restricting to women with estrogen receptor-positive tumors, when examining suggestive loci in an independent study, and when restricting to previously published risk loci. Additionally, the whole-genome prediction model also found no evidence to support an association.

Conclusion

Despite multiple complementary approaches, our study found no evidence that mortality in women with early onset breast cancer is influenced by germline variation.

     

A tandem duplication of <Emphasis Type="Italic">BRCA1</Emphasis> exons 1–19 through <Emphasis Type="Italic">DHX8</Emphasis> exon 2 in four families with hereditary breast and ovarian cancer syndrome

Background

Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer.

Methods

We conducted a case–control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk. Moderate and vigorous physical activities at ages 12–13, ages 14–17, ages 18–22, ages 23–29 and ages 30–34 were determined using the Nurses’ Health Study II Physical Activity Questionnaire. We estimated mean metabolic equivalent task hours/week for moderate, vigorous and total physical activities overall (ages 12–34), during adolescence (ages 12–17) and during early adulthood (ages 18–34). Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for total, moderate and strenuous recreational physical activities and breast cancer risk, by menopausal status.

Results

Overall, there was no significant association between total physical activity and subsequent breast cancer risk (OR_{Q4 vs. Q1} = 1.01, 95% CI 0.69–1.47; P-trend = 0.72). Moderate physical activity between ages 12–17 was associated with a 38% decreased risk of premenopausal breast cancer (OR_{Q4 vs. Q1} = 0.62; 95% CI 0.40–0.96; P-trend = 0.01). We found no association between exercise and breast cancer diagnosed after menopause.

Conclusions

These findings suggest that early-life physical activity is associated with a reduced risk of premenopausal breast cancer among BRCA mutation carriers.

Impact

Future prospective analyses, complemented by mechanistic evidence, are warranted in this high-risk population.

     

Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer

Purpose

To evaluate the sensitivity and specificity of different screening modalities in women with a family history of breast cancer.

Methods

Our blinded, prospective, comparative cohort analysis included three types of screening, mammography, ultrasound, and clinical breast examination once per year for 6 years. Eligible patients for this study were healthy women with ≥ 17% lifetime risk of breast cancer or with a mutation in BRCA1 or BRCA2.

Results

A total of 632 women were screened between 2002 and 2012 (each for 6 years). During the study, 30 women were diagnosed with breast cancer, with 10 of these diagnoses occurring between screening visits, and six of the 10 diagnosed women were gene carriers. The clinical presentation for the women diagnosed with breast cancer was followed until 2017. No consistent patterns for the diagnostic capacity of the different screening modalities were found, although mammography showed low sensitivity, whereas ultrasound showed better sensitivity in three of the six rounds. The specificity was high in mammography and improved in ultrasound over time. Most importantly, clinical breast examination provided no additional information toward the diagnosis of breast cancer.

Conclusion

Neither mammography nor ultrasound performed yearly were sensitive enough as standalone modalities, although high specificity was confirmed. Our findings indicate that high risk (> 29% life time risk) individuals and gene carriers can be screened biannually, using the same protocol as used in mutation carriers. Our results also suggest that low-risk groups (< 20%) may continue to be referred to population mammography screening program, while clinical breast examination may be omitted in all risk groups, and could be optional in gene carriers.

     

The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study

Purpose

Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women’s Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches.

Methods

To identify candidate gene–statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study.

Results

After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches.

Conclusions

We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women’s Health Initiative.

     

Association analysis of ERCC5 gene polymorphisms with risk of breast cancer in Han women of northwest China

Background

ERCC5 plays an important role in DNA damage repair. Mutations in it will lead to DNA repair defects and genomic instability. Its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and affect cancer susceptibility.

Methods

This study aims to evaluate the association between SNPs in ERCC5 and breast cancer susceptibility in Han women subjects genetically from northwest China. A total of 101 breast cancer patients and 101 healthy controls provided blood samples for analysis of ERCC5 rs17655 and rs751402 genotypes.

Results

After adjusting covariates, rs751402 homozygote AA and heterozygote AG were found to confer statistically significant protections (OR 0.052, 95 % CI 0.006–0.411, P = 0.005; OR 0.145, 95 % CI 0.067–0.315, P < 0.001, respectively) against breast cancer. Moreover, both of the dominant and recessive models of rs751402 also conferred a decreased risk of breast cancer (AA + AG vs. GG, OR 0.125, 95 % CI 0.060–0.261, P < 0.001; AA vs. GG + AG, OR 0.082, 95 % CI 0.010–0.648, P = 0.018, respectively).

Conclusions

The results indicate that the rs751402 in ERCC5 may affect the risk of breast cancer and show that it is associated with breast cancer characteristics in the Han population of northwest China. However, we found no significant differences between breast cancer patients and control subjects regarding ERCC5 rs17655 polymorphism in the studied population.