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.

10 Reads
  • Source
    • ", 2005 ; Olson et al . , 2005 ; Terry and Goodman , 2006 ; Ha et al . , 2007 ; Ahern et al . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Breast cancer is the most common malignancy of women in the world. The disease is caused by infectious and non-infectious, environmental and lifestyle factors. Tobacco smoke has been one of the most widely studied environmental factors with possible relevance to breast cancer. The purpose of this study was to assess the impact of tobacco smoking in breast cancer patients in a hospital based cohort and to establish prognostic implications if any. Materials and methods: A retrospective audit of 100 women with pathological diagnosis of invasive breast cancer was included in this study. The verbal questionnaire elicited information on current and previous history of exposure to smoking in addition to active smoking. All analyses were adjusted for potential confounders, including stage at presentation, alcohol intake, hormonal replacement therapy, oral contraceptive intake, obesity and menopausal status. Results: The mean age at presentation of breast cancer was 51.4 ± 10.86 years. Mean age of presentation was 53.1±11.5 and 45.7±11.9 years in never smokers and passive smokers, respectively. Age at presentation varied widely in patients exposed to tobacco smoke for >10 years in childhood from 40.3± 12.0 years to 47.7± 13.9 in patients exposed for > 20years as adults. Among passive smokers, 60.9% were premenopausal and 39.1% of patients were postmenopausal. In never smokers, 71.4% were post menopausal. Expression of receptors in non-smokers vs passive smokers was comparable with no significant differences. Metastatic potential in lung parenchyma was slightlyelevated in passive smokers as compared to never smokers although statistically non-significant. Conclusions: An inverse relationship exists between the intensity and duration of smoking and the age at presentation and poor prognostic factors. The results strongly suggest efforts should be taken to prevent smoking, encourage quitting and restrict exposure to second hand smoke in India.
    Full-text · Article · Aug 2015 · Asian Pacific journal of cancer prevention: APJCP
  • Source
    • "These observed effects of GST variants on hormone-related tumorigenesis is may be based on decreased conjugation of genotoxic estrogen quinones leading to elevated levels of DNA damage (Strange et al., 2001; Hachey et al., 2003). In addition, the GSTM1 and GSTT1 deletion as well as the GSTP1 rs1138272 variant, were suggested to affect tobacco smoke-related breast cancer risk (Terry and Goodman, 2006) pointing to the potentially critical role of GSTs in the elimination of exogenous carcinogenic compounds such as polycyclic aromatic hydrocarbons (Hayes and Pulford, 1995). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is a complex disease which is provoked by a multitude of exogenous and endogenous factors including genetic variations. Recent genome-wide association studies identified a set of more than 18 novel low penetrant susceptibility loci, however, a limitation of this powerful approach is the hampered analysis of polymorphisms in DNA sequences with a high degree of similarity to other genes or pseudo genes. Since this common feature affects the majority of the highly polymorphic genes encoding phase I and II enzymes the retrieval of specific genotype data requires adapted amplification methods. With regard to breast cancer these genes are of certain interest due to their involvement in the metabolism of carcinogens like exogenous genotoxic compounds or steroid hormones. The present review summarizes the observed effects of functional genetic variants of phase I and II enzymes in well designed case control studies to shed light on their contribution to breast cancer risk.
    Preview · Article · Nov 2012 · Frontiers in Genetics
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent cohort studies have suggested an increased risk of breast cancer with long duration of smoking, and with smoking initiation before first birth. Cigarette smoking may have both carcinogenic effects and antiestrogenic effects on the breast tissue. We decided to examine the relationship between different measures of smoking exposure and mammographic density. Lifetime smoking history was collected through interview and questionnaires among 907 postmenopausal participants in the Tromsø Mammography and Breast Cancer study. The mammograms were obtained from the governmental Norwegian Breast Cancer Screening Program. Mammograms were classified according to the percentage and absolute mammographic densities using a previously validated computer-assisted method. Sixty-five percent of the women reported having ever smoked cigarettes, while 34% were current smokers. After adjustment for age, age at first birth, parity, age at menopause, postmenopausal hormone therapy use, and body mass index, smoking was inversely associated with both measures of mammographic density (both trends P < 0.01). Both current smokers and former smokers had significantly lower adjusted mean percentage mammographic density compared with never smokers (P = 0.003 and P = 0.006, respectively). An inverse dose-response relationship with mammographic density was found between both the number of cigarettes and the number of pack-years smoked among current smokers. Current smokers who smoked 11 cigarettes or more daily had a 3.7% absolute (36% relative difference) lower percentage mammographic density compared with current smokers who smoked seven cigarettes or less daily (P = 0.008). When former smokers were stratified according to time since smoking cessation, we found that women who had stopped smoking less than 24 years ago had a significantly lower mean percentage mammographic density compared with never smokers (P < 0.001). We found modest inverse dose-response associations between numbers of cigarettes and of pack-years smoked and both measures of mammographic density among current smokers. Former smokers who had stopped smoking less than 24 years ago also had a statistically significantly lower mean percentage mammographic density when compared with never smokers. These findings are consistent with an antiestrogenic effect of cigarette smoking on the breast tissue.
    Full-text · Article · Oct 2007 · Breast cancer research: BCR
Show more