title: The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population.
abstract: Growing evidence suggests that the Thr241Met (T241M) polymorphism in the homologous recombination repair gene XRCC3 may alter DNA repair capacity and subsequent susceptibility to carcinogens. In a few studies of colorectal cancer (CRC), however, the results have been discrepant. A population-based nested case-control study including 140 cases and 280 cancer-free controls was conducted to evaluate the effect of XRCC3 polymorphism, environmental exposure, and family history (FH) on the risk of CRC. The variant allele frequency was low among the ethnic Han Chinese, but we observed a significant difference between cases (6.07%) and controls (2.32%). The analytic results of the unconditional logistic regression model adjusted by age, sex, alcohol intake, cigarette smoking, and FH of cancer in first-degree relatives showed a significantly increased risk of CRC (adjusted odds ratio [OR] = 3.13, 95% confidence interval [CI]: 1.41-6.95, P = 0.005) as the T/M and M/M genotypes compared with the T/T genotype, which changed weakly in consideration of the subsite (adjusted OR = 4.80, 95%CI: 1.77-12.98, P = 0.002 in colon cancer, adjusted OR = 2.41, 95%CI: 0.93-6.25, P = 0.071 in rectal cancer, respectively). Combined with environmental factors such as alcohol intake and cigarette smoking, no significant interaction could be found. However, the results revealed a significant association between FH of cancer in first-degree relatives and the risk of CRC (adjusted OR = 2.24, 95%CI: 1.18-4.25, P = 0.014). These results also suggest that XRCC3 T241M polymorphism and FH of cancer may be risk factors for CRC, and the XRCC3 241Met allele may be an effective biomarker for genetic susceptibility to CRC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.
authors.affiliation: Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, Hangzhou 310031, China.
authors.forename: Ming-Juan
authors.initials: MJ
authors.lastname: Jin
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Song
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Ma
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D013912:Threonine
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D013912:Threonine; D008715:Methionine