In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 915-915
Abstract:
The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer. Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case-control study conducted between 1998 and 2003 across seven centers in central and eastern Europe. The study centers were in the Czech Republic (Ceske, Prague, Olomouc, Brno), Poland (Lodz), Romania (Bucharest), and Russia (Moscow). Incident cases of primary kidney cancer were recruited and underwent an in-person interview in which detailed data were collected on demographics as well as work history and occupational exposure to chemical agents. Genes (cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT)) were selected for the present analysis based on their putative role in xenobiotic metabolism. Genotyping (874 cases and 2396 controls) was conducted with a GoldenGate® Oligo Pool All (OPA) assay by Illumina® and the 5’ nuclease assay (Taqman, Applied Biosystems). Haplotypes were calculated using fastPhase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusted for country of residence, age, and sex. We observed an increased risk of renal cell cancer (RCC) with two NAT1 SNPs (NAT1A40T, OR=1.36, CI 1.00, 1.86; NAT1R187Q, OR=1.65, CI 1.01, 2.71) and with CYP1B1V432L (OR=1.14, CI 1.01, 1.28). The slow (NAT1*14) phenotype was associated with increased risk of RCC (OR=1.69, CI 1.00-2.86) in comparison to normal phenotype (NAT1*4, *3, *11). Among persons with NAT1*14 phenotype, occupational exposure to trichloroethylene (OR=9.94, CI 1.15, 86.1) and chlorinated solvents (OR=9.79, CI 1.13, 84.8) conferred an increased risk of RCC. Among those with the CYP1B1V432L variant, occupational exposure to trichloroethylene (OR=1.68, CI 1.21, 2.34) and chlorinated solvents (OR=1.58, CI 1.14, 2.19) also had increased risk of RCC. These results require replication, but provide evidence that the relationship between certain agents and RCC may be modified by particular variants in xenobiotic metabolism genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 915.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-915
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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