Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 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, Yin Yao Shugart

Research output: Contribution to journalArticle

Abstract

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 1 AAversus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42-2.86; TA 1 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 trend <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.

Original languageEnglish (US)
Pages (from-to)530-536
Number of pages7
JournalCarcinogenesis
Volume32
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Double-Stranded DNA Breaks
Genetic Polymorphisms
Hepatocellular Carcinoma
Odds Ratio
Confidence Intervals
Genes
Multifactor Dimensionality Reduction
Hepatitis B Surface Antigens
Chromosome Aberrations
DNA Repair
Haplotypes
DNA Damage
Single Nucleotide Polymorphism
Genome
Population
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma. / Li, Rui; Yang, Yuan; An, Yu; Zhou, Yun; Liu, Yanhong; Yu, Qing; Lu, Daru; Wang, Hongyang; Jin, Li; Zhou, Weiping; Qian, Ji; Shugart, Yin Yao.

In: Carcinogenesis, Vol. 32, No. 4, 04.2011, p. 530-536.

Research output: Contribution to journalArticle

Li, R, Yang, Y, An, Y, Zhou, Y, Liu, Y, Yu, Q, Lu, D, Wang, H, Jin, L, Zhou, W, Qian, J & Shugart, YY 2011, 'Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma', Carcinogenesis, vol. 32, no. 4, pp. 530-536. https://doi.org/10.1093/carcin/bgr018
Li, Rui ; Yang, Yuan ; An, Yu ; Zhou, Yun ; Liu, Yanhong ; Yu, Qing ; Lu, Daru ; Wang, Hongyang ; Jin, Li ; Zhou, Weiping ; Qian, Ji ; Shugart, Yin Yao. / Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma. In: Carcinogenesis. 2011 ; Vol. 32, No. 4. pp. 530-536.
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abstract = "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 1 AAversus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95{\%} CI = 1.42-2.86; TA 1 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 trend <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.",
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T1 - Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma

AU - Li, Rui

AU - Yang, Yuan

AU - An, Yu

AU - Zhou, Yun

AU - Liu, Yanhong

AU - Yu, Qing

AU - Lu, Daru

AU - Wang, Hongyang

AU - Jin, Li

AU - Zhou, Weiping

AU - Qian, Ji

AU - Shugart, Yin Yao

PY - 2011/4

Y1 - 2011/4

N2 - 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 1 AAversus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42-2.86; TA 1 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 trend <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.

AB - 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 1 AAversus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42-2.86; TA 1 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 trend <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.

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