Carcinogenesis Advance Access originally published online on August 18, 2008
Carcinogenesis 2008 29(11):2112-2119; 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
2 Department of Urology
3 Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
* To whom correspondence should be addressed. Department of Epidemiology, Unit 1340, The University of Texas M. D. Anderson Cancer Center, 1155 Hermann Pressler Boulevard, Houston, TX 77030, USA. Tel: +1 713 745 2485; Fax: +1 713 792 4657; Email: xwu{at}mdanderson.org
In this population-based case–control study with 325 Caucasian renal cell carcinoma (RCC) patients and 335 controls matched to cases by age, gender and county of residence, we evaluated the associations between 13 potential functional polymorphisms in nine major nucleotide excision repair (NER) genes and RCC risk. In individual single nucleotide polymorphism 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'untranslated region 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.
Abbreviations: CART, classification and regression tree; CI, confidence interval; FDR, false discovery rate; NER, nucleotide excision repair; OR, odds ratio; RCC, renal cell carcinoma; SNP, single nucleotide polymorphism; UTR, untranslated region
Received June 9, 2008; revised August 5, 2008; accepted August 5, 2008.