Is the Association between Cigarette Smoking and Breast Cancer Modified by Genotype? A Review of Epidemiologic Studies and Meta-analysis

Department of Epidemiology, Emory University School of Public Health, Atlanta, GA 30322, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 05/2006; 15(4):602-11. DOI: 10.1158/1055-9965.EPI-05-0853
Source: PubMed


Epidemiologic studies have examined the association between cigarette smoking and breast cancer risk according to genotype with increasing frequency, commensurate with the growing awareness of the roles genes play in detoxifying or activating chemicals found in cigarette smoke and in preventing or repairing the damage caused by those compounds. To date, approximately 50 epidemiologic studies have examined the association between smoking and breast cancer risk according to variation in genes related to carcinogen metabolism, modulation of oxidative damage, and DNA repair. Some of the findings presented here suggest possible effect modification by genotype. In particular, 14 epidemiologic studies have tended to show positive associations with long-term smoking among NAT2 slow acetylators, especially among postmenopausal women. Summary analyses produced overall meta-relative risk (RR) estimates for smoking of 1.2 [95% confidence interval (95% CI), 1.0-1.5] for rapid acetylators and 1.5 (95% CI, 1.2-1.8) for slow acetylators. After stratification by menopausal status, the meta-RR for postmenopausal slow acetylators was 2.4 (95% CI, 1.7-3.3), whereas similar analyses for the other categories showed no association. In addition, summary analyses produced meta-RRs for smoking of 1.1 (95% CI, 0.8-1.4) when GSTM1 was present and 1.5 (95% CI, 1.1-2.1) when the gene was deleted. Overall, however, interpretation of the available literature is complicated by methodologic limitations, including small sample sizes, varying definitions of smoking, and difficulties involving single nucleotide polymorphism selection, which likely have contributed to the inconsistent findings. These methodologic issues should be addressed in future studies to help clarify the association between smoking and breast cancer.

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    Frontiers in Genetics 11/2012; 3:258. DOI:10.3389/fgene.2012.00258
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    • "Mammographic density is an independent risk factor for breast cancer, and lower mammographic density could suggest lower risk for breast cancer [18,19]. One of the suggested mechanisms for how smoking might increases the risk of breast cancer is carcinogenic effects of constituents in tobacco smoke on the breast tissue [1-3]. It is possible that this suggested mechanism does not affect mammographic density, and thus would not influence mammographic density as measured in our study. "
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