Abstract

BackgroundPlausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent.MethodsWe used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake.ResultsAmong 102,927 women recruited 2003–2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03–1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08–1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07–1.41; P = 0.004) for starting smoking 1–4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12–1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96–1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001).ConclusionsSmoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease.

Highlights

  • Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent

  • Authors of more recent epidemiological analyses have reported modest raised risks with current [8,9,10,11,12,13,14,15,16,17,18,19] or former [8,9,10,11,12,13,14,15, 20] smoking, but questions remain about the extent to which this association is a consequence of confounding by alcohol use, whether risk is increased if smoking starts in adolescence or before first childbirth, and whether risk is modified by family history of breast cancer [1, 2]

  • Nor did we find significant interactions with birth cohort (P = 0.092), body mass index (BMI) at age 20 years (P = 0.55) or post-menopausal ages (P = 0.26), but we did see a significant interaction with family history of breast cancer (P = 0.038)

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Summary

Introduction

Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent. The carcinogenic potential of tobacco smoke is unarguable [1, 2], and there are plausible biological reasons why smoking could affect breast cancer risk [2,3,4,5]. Authors of reviews of the association between cigarette smoking and breast cancer up to 2004 did not, generally find conclusive evidence for a causal relationship in humans [5,6,7]. We examined the risk of invasive breast cancer in relation to

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