Journal Article

Genetic polymorphisms in DNA double-strand break repair genes <i>XRCC5</i>, <i>XRCC6</i> and susceptibility to hepatocellular carcinoma

Rui Li, Yuan Yang, Yu An, Yun Zhou, Yanhong Liu, Qing Yu, Daru Lu, Hongyang Wang, Li Jin, Weiping Zhou, Ji Qian and Yin Yao Shugart

in Carcinogenesis

Volume 32, issue 4, pages 530-536
Published in print April 2011 | ISSN: 0143-3334
Published online February 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr018
Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma

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Environmental risk factors cause DNA damages. Imprecise DNA repair leads to chromosome aberrations, genome destabilization and hepatocarcinogenesis. Ku is a key DNA double-strand break repair protein. We hypothesized that the genetic variants in Ku subunits encoding genes, XRCC5/XRCC6, may contribute to hepatocellular carcinoma (HCC) susceptibility. We genotyped 13 common single nucleotide polymorphisms (SNPs) in XRCC5 and XRCC6 and evaluated their associations with HCC risk in 689 pathologically confirmed cases and 690 cancer-free controls from a Chinese population. We found that a significantly reduced risk for HCC was associated with XRCC5 rs16855458 [odds ratio (OR) = 0.59; 95% confidence interval (CI) = 0.43−0.81; CA + AA versus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42−2.86; TA + AA versus TT) even after Bonferroni correction (Pcorrected = 0.026 and 0.002, respectively). The effects of rs16855458 (OR = 0.57; 95% CI = 0.37−0.86, P = 0.008) and rs9288516 (OR = 1.86; 95% CI = 1.19−2.90, P = 0.007) were more significant in hepatitis B surface antigen-infected subjects than non-infected subjects. The haplotype-based analysis revealed that in XRCC5, AA in block 1 (OR = 0.63; 95% CI = 0.48−0.83) and CGGTT in block 2 (OR = 0.52; 95% CI = 0.39−0.69) were associated with decreased HCC risk (Pcorrected = 0.013 and <0.001, respectively). The aforementioned two SNPs exhibited a significant cumulative risk effect (Ptrend < 0.001). Additionally, potential interaction among XRCC5 rs9288516 and rs2267437, rs5751131 in XRCC6 was indicated by the multifactor dimensionality reduction analysis. In conclusion, XRCC5 variants may play a role in determining individual’s HCC susceptibility, which warranted validation in larger studies.

Journal Article.  5936 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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