Abstract 2640: Risk of cytochrome P450 1B1 missense polymorphisms in renal cell carcinoma

Abstract

Abstract In male kidney, 4-hydroxy-estradiol has been shown to play a role in the carcinogenesis process. This metabolite is formed from estradiol and due to the hydroxylation activity of the cytochrome P450 1B1 (CYP1B1) enzyme. Prior reports show polymorphisms of CYP1B1 to result in higher catalytic activity and thus, we hypothesize that single nucleotide polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell. To test this hypothesis, the genetic distributions of four missense CYP1B1 polymorphisms were analyzed in 383 normal healthy subjects and 384 sporadic renal cell carcinoma (RCC) cases by sequence-specific PCR and sequencing. All subjects were men and from a Caucasian population. The polymorphic sites evaluated were at codons 48 (ArgαGly, rs10012), 119 (AlaαSer, rs1056827), 432 (LeuαVal, rs1056836), and 453 (AsnαSer, rs1800440). Results of these experiments demonstrate a trend for the codon 119 Ser/Ser genotype to be a risk for RCC (χ2, P=0.09). Odds ratio for the Ser/Ser genotype was calculated as 1.85 with 95% confidence interval of 1.07-3.20 as compared to the Ala/Ala genotype. The Leu allele on codon 432 was also found to approach significance as a risk for RCC as compared to Val (χ2, P=0.09). Codons 119 and 432 were observed to be linked (R2=0.25) and haplotype analyses show Ala and Val, representing non-risk alleles at these sites, respectively, to be significantly reduced in RCC cases (P=0.06). No association was found however, when analyzing polymorphic sites with clinical stage of RCC. These results demonstrate missense polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2640. doi:1538-7445.AM2012-2640