Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

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Very high concentrations of naturally occurring radionuclides are encountered in Finnish groundwaters and wells. Radon ingested through drinking water can cause considerable radiation to the stomach. We assessed the effect of natural uranium and other radionuclides in drinking water on the risk of stomach cancer. Subjects (n ‫؍‬ 144,627) in the base cohort had lived outside the municipal tap water system during 1967-1980. A subcohort of 4,590 subjects was formed for use as a reference group by random sampling of the base cohort, with stratification by age and sex. Within the subcohort, 371 subjects had used drinking water from drilled wells prior to 1981. Stomach cancer cases within the subcohort were identified through a cancer registry, and cases using water from drilled wells were selected. Activity concentrations of radon, radium-226 and natural uranium in the drinking water were analyzed using radiochemical and alpha spectrometric methods. The median activity concentration of radon in well water was 130 Bq/l for both the 88 stomach cancer cases and the 274 subjects in the subcohort. Median radium concentrations were 0.007 Bq/l for cases and 0.010 Bq/l for the subcohort, with a median uranium concentration of 0.07 Bq/l for both groups. Risk of stomach cancer was not associated with exposure to radon or other radionuclides. Key words: stomach cancer; radon; radium; uranium; radiation effects; water Although radiation is a well-established cause of cancer and its carcinogenic effects are known in considerable detail, epidemiologic studies have primarily dealt with high doses of external radiation. The most important contribution of natural radiation for most populations is from inhaled radon (generic term used commonly to refer to the isotope radon-222) progeny. High residential levels of radon increase the risk of lung cancer, but the effects of other types of internal exposure to natural radiation have remained largely unknown. 1 Everybody is exposed to natural radionuclides, including uranium, thorium decay chains and potassium-40. Radiation exposure results from intake through diet and drinking water as well as inhalation of radioactive gases, such as radon. Typically, internal exposure to natural radioisotopes other than radon is negligible (on average 140 Sv/year), but there are populations with substantially increased exposures to radionuclides from the uranium and thorium series, while variability in exposure to potassium-40 is much more limited. 2 Our study deals with radon, radium and uranium, which are the most important radionuclides contributing to natural radioactivity in water.Exposures to natural radionuclides through drinking water substantially exceeding normal levels occur in some circumstances. Due to granitoid bedrock and groundwater characteristics, concentrations of several natural radionuclides in groundwater in Finland are exceptionally high, and exposure through wells drilled in bedrock is frequently much higher than in other parts of the world. Among Finns, who use drinking water fro...

We evaluated the influence of several DNA repair gene polymorphisms on the frequency of chromosomal aberrations (CAs) analyzed in peripheral lymphocytes, using the fluorescence in situ hybridization technique. The CA data were obtained from an earlier study of 84 healthy nonsmokers (48 women and 36 men) carefully characterized for indoor radon exposure. The frequency of translocations showed a wide interindividual variability, which was only partly explained by age. To investigate the potential role of DNA repair polymorphisms in this variation, genotypes of DNA repair genes OGG1 (codon 326), XPD (codon 751), XRCC1 (X-ray repair cross-complementing group 1) (codons 194, 280, and 399), and XRCC3 (X-ray repair cross-complementing group 3) (codon 241) were determined from leukocyte DNA using polymerase chain reaction-based methods. Negative binomial regression models were applied to evaluate the effect of the polymorphisms and other factors (age, gender, radon exposure, and medical exposure) on the frequency of CAs. No interactions between genotypes and radon, medical exposure, or gender were found. Carriers of the XRCC1 codon 280His variant allele had a two-fold increase (frequency ratio [FR] = 2.01, 95% confidence interval [CI] = 1.01-3.98; P = 0.046) in unstable exchanges (dicentrics and ring chromosomes). In addition, the XRCC3 codon 241 homozygous variant genotype (Met/Met) was associated with an increase (FR = 1.70, 95% CI = 1.06-2.74; P = 0.028) in two-way translocations when age was taken into account in the analysis. Our data suggest that the XRCC1 280His and XRCC3 241Met alleles affect individual CA levels, most probably via influencing the DNA repair phenotype.

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