Tagging single nucleotide polymorphisms in excision repair cross-complementing group 1 (ERCC1) and risk of primary lung cancer in a Chinese population.

Pharmacogenet Genomics 2007 Jun;17(6):417-23

Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, China.

Background And Objective: Low nucleotide excision repair (NER) capacity has been associated with increased risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is one of the NER core enzymes, and polymorphisms in ERCC1 may lead to altered repair function of the enzyme and therefore confer predisposition to cancer. The goal of this study was to test the hypothesis that common variants in ERCC1 were associated with lung cancer risk.

Methods: The genotyping analyses for 7 selected single nucleotide polymorphisms in ERCC1 using the TaqMan assay was conducted in a case-control study of 1010 patients with incident lung cancer and 1011 cancer-free controls in a Chinese population.

Results: We found that the variant genotypes of the rs3212948 C allele were associated with significantly decreased risk of lung cancer [adjusted odds ratio (OR)=0.73 (95% CI=0.60-0.88) for CG; 0.96 (95% CI=0.65-1.41) for CC and 0.76 (95% CI=0.63-0.91) for CG/CC, compared with the GG genotype]. Similarly, a significant protective effect was also evident for the variant genotypes of rs1007616 C/T [adjusted OR=0.72 (95% CI=0.59-0.89) for CT; 0.90 (95% CI=0.61-1.35) for TT and 0.75 (95% CI=0.62-0.91) for CT/TT, compared with the CC genotype]. Stratified analysis revealed that the protective effects of these 2 single nucleotide polymorphisms were both more evident among young patients and patients without family history of cancer. Consistently, when assessing each unique haplotype compared with the most common haplotype 'TAGCACG', lung cancer risk was significantly decreased among patients who carried the haplotype 'TCCCATT' with the variant rs3212948C and rs1007616T alleles (P value=0.0340, P-sim=0.0325, adjusted OR=0.78; 95% CI=0.63-0.97).

Conclusion: These findings indicate that ERCC1 polymorphisms may contribute to the etiology of lung cancer. Further functional studies were warranted to elucidate the mechanism of the associations.

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http://dx.doi.org/10.1097/01.fpc.0000239975.77088.17DOI Listing
June 2007
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