Association of XRCC1 polymorphisms and risk of differentiated thyroid carcinoma: a case-control analysis.
BACKGROUND
Numerous single-nucleotide polymorphisms (SNPs) of the DNA repair gene XRCC1 have been described. These SNPs have been increasingly studied in the epidemiology of various cancer types. In this study we evaluated the risk association between six common SNPs of the XRCC1 gene and differentiated thyroid carcinoma (DTC).


METHODS
We conducted a case-control study of 251 subjects with DTC, 145 subjects with benign thyroid disease, and 503 cancer-free controls. Polymerase chain reaction-restriction fragment length polymorphism assays were performed for genotyping. Multivariate logistic regression analysis was performed for risk estimation. Expectation-maximization algorithm and bayesian methods were used to estimate haplotype frequencies.


RESULTS
Multivariate analysis demonstrated an increased risk of DTC for the Arg194Trp heterozygous polymorphic (CT) genotype (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 0.9-2.1). Multivariate analysis demonstrated a decreased risk of DTC for the Arg399Gln homozygous polymorphic (AA) genotype (OR: 0.5, 95% CI: 0.3-0.8) and the polymorphic (A) allele (OR: 0.7, 95% CI: 0.5-1.0). Compared to the most commonly observed haplotype (CGTCGA), multiple haplotypes were associated with a significantly increased risk of DTC, with the CGTTGG haplotype demonstrating the strongest association (OR: 5.0, 95% CI: 1.9-13.2).


CONCLUSIONS
The XRCC1 194Trp variant allele may be associated with increased risk of DTC, while the XRCC1 399Gln variant allele may be associated with decreased risk of DTC. The utility of XRCC1 haplotypes in predicting DTC risk deserves further investigation with direct haplotype measurement.
Ho
Tang
T
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Li
Guojun
G
Lu
Jiachun
J
Zhao
Chong
C
Wei
Qingyi
Q
Sturgis
Erich M
EM
D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013964:Thyroid Neoplasms / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human