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

Abstract

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, f50 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 longterm 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. (Cancer Epidemiol Biomarkers Prev 2006;15(4):602 -11)

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

“…The risk associated with smoking exposure may also vary according to genetic susceptibility, as found in a number of studies (reviewed by Terry and Goodman 42 , which indeed might explain part of the differences observed across EPIC , ever use of oral contraceptives (yes/non/missing), ever use of menopausal hormone therapy (yes/no/missing), menopausal status at baseline (premenopausal/postmenopausal/unknown), parity and age at first full-term pregnancy (nulliparous/parous and age at FFTP 25 years/parous and age at FFTP < 25 years/missing), age at menarche (<12/12/13/ 14 years), alcohol consumption (0/0-10/>10 g ethanol), physical activity (inactive, moderately inactive, moderately active, active, missing); in the assessment of smoking during a specific period, smoking during the other life periods was adjusted for. 3 Only among parous women.…”

Active and passive smoking, IL6, ESR1, and breast cancer risk

“…Studies have examined genes that regulate metabolizing enzymes such as NAT2 and CYP1A1 [2,5,[8][9][10]. Other genes such as MnSOD have been examined because it may influence susceptibility to cigarette smoking because of their influence on oxidative stress [11,12].…”

Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

“…Review of these studies show negative, positive or null association between smoking and breast malignancies (Palmer and Rosenberg, 1993;Hamajima et al, 2002;Fink and Lash, 2003). More recent studies suggest that smoking does not decrease but may enhance breast cancer risk depending upon the duration and frequency of smoking, age at the commencement of smoking and smoking before a first full-term pregnancy (Terry and Rohan, 2002;Gram et al, 2005;Terry and Goodman, 2006). Role of passive smoking in breast cancer has also been investigated and while some studies have found no association (Egan et al, 2002), others report a positive association between passive smoking and breast cancer risk (Morabia et al, 1996;Johnson et al, 2000).…”

“…Studies have also examined if polymorphism of detoxifying, activating, or DNA damage-repair genes influence the breast cancer risk in smokers (Terry and Goodman, 2006). The results show either a positive or null association between long-term smoking and N-acetyltransferase (NAT-2), CYP1A1, glutathione S-transferase, sulfotransferase 1A1 genes (Terry and Goodman, 2006).…”

“…The results show either a positive or null association between long-term smoking and N-acetyltransferase (NAT-2), CYP1A1, glutathione S-transferase, sulfotransferase 1A1 genes (Terry and Goodman, 2006). Studies of the BER enzyme, XRCC1, have shown a positive association of long-term smoking with breast cancer risk (Duell et al, 2001;Terry and Rohan, 2002;Patel et al, 2005;Pachkowski et al, 2006).…”