XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish case-control study.
BACKGROUND
It has been suggested that individuals with reduced DNA repair capacities might have increased susceptibility to environmentally induced cancer. In this study, we evaluated if polymorphisms in DNA repair genes XRCC1 (Arg280His, Arg399Gln) and XPD (Lys751Gln) modify individual breast cancer risk, with emphasis on tobacco smoking.


METHODS
The study population consisted of 483 incident breast cancer cases and 482 population controls of Finnish Caucasian origin. The genotypes were determined by PCR-RFLP-based methods. Odds ratio (OR) and confidence intervals (CIs) were calculated by unconditional logistic regression analyses.


RESULTS
No statistically significant overall effect in the breast cancer risk was seen for any of the studied polymorphisms. However, a significant increase in breast cancer risk was seen among ever smoking women if they carried at least one XRCC1-399 Gln allele (OR 2.33, 95% CI 1.30-4.19, pint 0.025) or XPD-751 Gln/Gln genotype (OR 2.52, 95% CI 1.27-5.03, pint 0.011) compared to smoking women not carrying these genotypes. The risks were found to be confined to women smoking at least five pack-years; the respective ORs were 4.14 (95% CI 1.66-10.3) and 4.41 (95% CI 1.62-12.0). Moreover, a significant trend of increasing risk with increasing number of the putative at-risk genotypes (p for trend 0.042) was seen. Women with at least two at-risk genotypes had an OR of 1.54 (95% CI 1.00-2.41) compared to women with no at-risk genotypes. Even higher estimates were seen for ever actively smoking women with at least two at-risk genotypes.


CONCLUSIONS
Our results do not indicate a major role for XRCC1 and XPD polymorphisms in breast cancer susceptibility, but suggest that they may modify the risk especially among smoking women.
Metsola
Katja
K
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland. katja.metsola@ttl.fi
Kataja
Vesa
V
Sillanpää
Pia
P
Siivola
Päivi
P
Heikinheimo
Liisa
L
Eskelinen
Matti
M
Kosma
Veli-Matti
VM
Uusitupa
Matti
M
Hirvonen
Ari
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human