TY - JOUR
T1 - Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma
AU - Li, Chunying
AU - Liu, Zhensheng
AU - Wang, Li E.
AU - Strom, Sara S.
AU - Lee, Jeffrey E.
AU - Gershenwald, Jeffrey E.
AU - Ross, Merrick I.
AU - Mansfield, Paul F.
AU - Cormier, Janice N.
AU - Prieto, Victor G.
AU - Duvic, Madeleine
AU - Grimm, Elizabeth A.
AU - Wei, Qingyi
N1 - Funding Information:
We thank Margaret Lung, Cesar A. Maldonado, and Amanda Franco for assistance in recruiting the subjects; Zhaozheng Guo, Yawei Qiao, Jianzhong He and Kejing Xu for laboratory assistance; Joanne Sider for assistance in preparing the manuscript; Susan Eastwood for scientific editing. This study was in part supported by the National Institutes of Health National Cancer Institute grants R01 CA 100264 (Q.W.) and P50 CA 093459 (E.A.G.), the National Institute of Environmental Health Sciences grant R01 ES11740 (Q.W.) and P30 CA16672 (M. D. Anderson Cancer Center).
PY - 2006/9
Y1 - 2006/9
N2 - Sunlight causes various kinds of DNA damage, including oxidative lesions that are removed effectively by the base excision repair (BER) pathway, in which ADPRT, XRCC1 and APE1 play a key role. However, genetic variation in these genes may alter their functions. We hypothesized that ADPRT, XRCC1 and APE1 polymorphisms are associated with risk of cutaneous melanoma (CM). In a hospital-based case-control study of 602 CM patients and 603 cancer-free control subjects frequency matched on age, sex and ethnicity, we genotyped for three non-synonymous single nucleotide polymorphisms (SNPs) (i.e. the ADPRT Val762Ala, XRCC1 Arg399Gln and APE1Asp148Glu) and assessed their associations with risk of CM. We found no significant difference in the allele frequencies between cases and controls for any of these three SNPs. However, we found that, compared with the APE1 Asp/Asp genotype, a significantly decreased risk of CM was associated with the APE1 Asp/Glu [adjusted odds ratio (OR), 0.60; 95% confidence interval (CI), 0.41-0.86], Glu/Glu (OR, 0.58; 95% CI, 0.38-0.88) and combined APE1 Asp/Glu+Glu/Glu (OR, 0.59; 95% CI, 0.42-0.83) genotypes, but not for other XRCC1 variant genotypes. Moreover, there was evidence for a possible gene-gene interaction between XRCC1 and APE1 variants in the association with risk of CM (P = 0.030). We conclude that the APE1 Glu variant may have an effect or interact with XRCC1 in the etiology of CM or in linkage disequilibrium with other untyped protective alleles. Larger studies with more SNPs in the BER genes are needed to verify these findings.
AB - Sunlight causes various kinds of DNA damage, including oxidative lesions that are removed effectively by the base excision repair (BER) pathway, in which ADPRT, XRCC1 and APE1 play a key role. However, genetic variation in these genes may alter their functions. We hypothesized that ADPRT, XRCC1 and APE1 polymorphisms are associated with risk of cutaneous melanoma (CM). In a hospital-based case-control study of 602 CM patients and 603 cancer-free control subjects frequency matched on age, sex and ethnicity, we genotyped for three non-synonymous single nucleotide polymorphisms (SNPs) (i.e. the ADPRT Val762Ala, XRCC1 Arg399Gln and APE1Asp148Glu) and assessed their associations with risk of CM. We found no significant difference in the allele frequencies between cases and controls for any of these three SNPs. However, we found that, compared with the APE1 Asp/Asp genotype, a significantly decreased risk of CM was associated with the APE1 Asp/Glu [adjusted odds ratio (OR), 0.60; 95% confidence interval (CI), 0.41-0.86], Glu/Glu (OR, 0.58; 95% CI, 0.38-0.88) and combined APE1 Asp/Glu+Glu/Glu (OR, 0.59; 95% CI, 0.42-0.83) genotypes, but not for other XRCC1 variant genotypes. Moreover, there was evidence for a possible gene-gene interaction between XRCC1 and APE1 variants in the association with risk of CM (P = 0.030). We conclude that the APE1 Glu variant may have an effect or interact with XRCC1 in the etiology of CM or in linkage disequilibrium with other untyped protective alleles. Larger studies with more SNPs in the BER genes are needed to verify these findings.
UR - http://www.scopus.com/inward/record.url?scp=33747877809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747877809&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgl042
DO - 10.1093/carcin/bgl042
M3 - Article
C2 - 16621887
AN - SCOPUS:33747877809
SN - 0143-3334
VL - 27
SP - 1894
EP - 1901
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -