Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer.
INTRODUCTION
Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1, CYP2A6) or in DNA repair (XRCC1, APEX1, XRCC3 and XPD) in breast cancer development.


METHODS
We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women.


RESULTS
We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (all Ptrend < 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98-25.59)).


CONCLUSIONS
Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis that CYP1A1 Ile462Val, in association with long periods of active smoking, could be a breast cancer risk factor.
['Verde|Zoraida|Z|', 'Santiago|Catalina|C|', 'Chicharro|Luis Miguel|LM|', 'Reinoso-Barbero|Luis|L|', 'Tejerina|Alejandro|A|', 'Bandrés|Fernando|F|', 'Gómez-Gallego|Félix|F|']
D000328:Adult D000368:Aged D001940:Breast D001943:Breast Neoplasms D016022:Case-Control Studies D019363:Cytochrome P-450 CYP1A1 D065637:Cytochrome P-450 CYP2A6 D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase D004268:DNA-Binding Proteins D005260:Female D020022:Genetic Predisposition to Disease D006801:Humans D008875:Middle Aged D011110:Polymorphism, Genetic D012907:Smoking D000076105:X-ray Repair Cross Complementing Protein 1 D051759:Xeroderma Pigmentosum Group D Protein
breast cancer CYP1A DNA repair genes long-term smoking