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Polymorphisms of the CYP1B1 Gene as Risk Factors for Human Renal Cell Cancer

¹ Department of Urology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, California; ² Department of Urology and ³ Second Department of Pathology, Kagoshima University Faculty of Medicine, Kagoshima, Japan; ⁴ Department of Clinical Genetics, Tenshi Hospital, Kitaku, Sapporo, Japan; and ⁵ Department of Obstetrics and Gynecology, School of Medicine, Hokkaido University, Kitaku, Sapporo, Japan

Purpose: CYP1B1 activates various environmental carcinogens in human tissues, including renal tissues. We hypothesize that certain polymorphisms of the CYP1B1 gene are risk factors for renal cell cancer. The rationale for this hypothesis is that chemical procarcinogenic compounds require metabolic activation by oxidative enzymes such as CYP1B1 to be transformed into potentially carcinogenic forms. To test this hypothesis, we investigated the genotypic distributions of six different loci on the CYP1B1 gene and their association with renal cell cancer.

Experimental Design: DNA from 211 cases of human renal cell cancer and 200 healthy controls was analyzed by sequence-specific PCR and direct DNA sequencing to determine the genotypic frequencies of six different polymorphic loci on the CYP1B1 gene.

Results: The results of this study demonstrate that the frequencies of genotype 119T/T and genotype 432G/G were significantly higher in renal cell cancer patients compared with healthy normal controls. The relative risks were calculated as 3.01 and 2.17 for genotypes 119T/T and 432G/G, respectively, in renal cell carcinoma patients. These genotypic distributions were also significantly different between male and female patients. The relative risks of genotype 119T/T were calculated as 3.95 in males and 1.92 in females, and the relative risks of genotype 432G/G were calculated as 2.81 in males and 1.35 in females.

Conclusions: The present study demonstrates for the first time that the polymorphisms at codons 119 and 432 may be risk factors for renal cancer, especially in the male population.

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