Protective Effect of Cigarette Smoking on Breast Cancer Risk in Women With BRCA1 or BRCA2 Mutations???

Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.

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Cigarette smoking and breast cancer risk in relation to joint estrogen and progesterone receptor status: a case-control study in Japan

SpringerPlus ◽

10.1186/2193-1801-3-65 ◽

2014 ◽

Vol 3 (1) ◽

pp. 65 ◽

Cited By ~ 18

Author(s):

Yoshikazu Nishino ◽

Yuko Minami ◽

Masaaki Kawai ◽

Kayoko Fukamachi ◽

Ikuro Sato ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cigarette Smoking ◽

Progesterone Receptor ◽

Case Control Study ◽

Case Control ◽

Progesterone Receptor Status ◽

Control Study ◽

Estrogen And Progesterone Receptor

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Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study

BMJ ◽

10.1136/bmj.l2327 ◽

2019 ◽

pp. l2327 ◽

Cited By ~ 15

Author(s):

Rebecca C Richmond ◽

Emma L Anderson ◽

Hassan S Dashti ◽

Samuel E Jones ◽

Jacqueline M Lane ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Protective Effect ◽

Sleep Duration ◽

Breast Cancer Diagnosis ◽

Mendelian Randomisation ◽

Uk Biobank ◽

Multivariable Regression ◽

Insomnia Symptoms

Abstract Objective To examine whether sleep traits have a causal effect on risk of breast cancer. Design Mendelian randomisation study. Setting UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study. Participants 156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis. Exposures Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits. Main outcome measure Breast cancer diagnosis. Results In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy. Conclusions Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.

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