Carcinogenesis Advance Access published online on August 18, 2008
Carcinogenesis, doi:10.1093/carcin/bgn189
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Case-Control Analysis of Nucleotide Excision Repair Pathway and the Risk of Renal Cell Carcinoma
1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
2 Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
3 Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Correspondence should be addressed to: Xifeng Wu, M.D., Ph.D., Department of Epidemiology, Unit 1340, The University of Texas M.D. Anderson Cancer Center, 1155 Hermann Pressler Blvd., Houston, Texas 77030. Telephone: (713) 745-2485, Fax: (713) 792-4657, E-mail: xwu{at}mdanderson.org
In this population-based case control study with 325 Caucasian RCC patients and 335 controls matched to cases by age, gender and county of residence, we evaluated the associations between thirteen potential functional polymorphisms in nine major nucleotide excision repair (NER) genes and renal cell carcinoma (RCC) risk. In individual SNP analysis, after adjustment for multiple comparisons, a significantly decreased RCC risk was observed for the heterozygous genotype of XPD Asp312Asn [Odds Ratio (OR) = 0.62; 95% confidence interval (CI) 0.43-0.90] and for the heterozygous and homozygous variant genotypes combined in a dominant model (OR = 0.64; 95% CI 0.46-0.89). The heterozygous AG genotype of XPA 5’UTR was at 1.78-fold increased risk (95% CI 1.18-2.69) and the risk reached 2.43 fold (95% CI 1.57-3.75) for the homozygous variant GG genotype; the risk was significant both in the dominant model and in the recessive model. In joint analysis, compared with individuals with fewer than five adverse alleles, individuals with five (OR = 1.17; 95% CI 0.71-1.93), six (OR = 1.66; 95% CI 1.03-2.67), seven or more (OR = 1.85; 95% CI 1.16-2.95) exhibited a progressively increased risk of RCC (P-for trend = 0.004). Further, there were significant interactions between NER pathway genes and sex, hypertension and obesity (all P-for interaction<0.05). Our results strongly support that common sequence variants of the NER pathway genes predispose susceptible individuals to increased risk of RCC and that the association may be modified by gender, history of hypertension, and obesity. These results need to be replicated in larger studies.
Key Words: Nucleotide excision repair • renal cell carcinoma • case-control study
Received June 9, 2008; revised August 5, 2008; accepted August 5, 2008.