Selected DNA repair polymorphisms and gastric cancer in Poland.
Impaired DNA repair capacity may adversely affect cancer risk, particularly in subjects exposed to DNA damaging carcinogens, as found in tobacco smoke, or among subjects deficient for protective factors, as found in fruits and vegetables. We studied tobacco use, fruit and vegetable intake, and common non-synonymous single nucleotide polymorphisms in four DNA repair genes in relation to gastric cancer risk, in a population-based, case-control study of 281 incident gastric cancer cases and 390 controls, in Warsaw, Poland. Multivariate logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Increased risks of gastric cancer were found for smokers (OR=3.1, CI=1.9-5.1 for pack-years>or=40 versus never smokers) and subjects with low fruit intake (OR=2.2, CI=1.3-3.6 for 1st versus 4th quartile); risk associated with vegetable intake was not statistically significant. Allele frequencies among the controls were consistent with those previously reported for the 5 polymorphisms studied: XRCC1-Arg399Gln, XPD-Lys751Gln, MGMT-Ile143Val, Leu84Phe, and XRCC3-Thr241Met. None of the studied polymorphisms were independently associated with gastric cancer risk. Smoking-associated risks, however, were greatest for carriers of the XRCC1-399 ArgArg genotype (Pinteraction=0.004). Risks associated with low intake of fruits or vegetables tended to be modified by selected polymorphisms in XRCC1, XPD and MGMT (Pinteraction=0.1-0.2). Risk modification was not found for the other repair polymorphisms. Selected DNA repair polymorphisms did not have independent effects on gastric cancer risk; however, they may modify smoking- and probably diet-related risks for this disease. These results need replication in larger epidemiological studies of gastric cancer.
Huang
Wen-Yi
WY
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. huangw@mail.nih.gov
Chow
Wong-Ho
WH
Rothman
Nat
N
Lissowska
Jolanta
J
Llaca
Victor
V
Yeager
Meredith
M
Zatonski
Witold
W
Hayes
Richard B
RB
D000328:Adult; D000368:Aged; D003062:Codon / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004032:Diet; D005260:Female; D005638:Fruit; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012907:Smoking; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014675:Vegetables
D003062:Codon