Polymorphism with the Susceptibility to Renal

Except for hereditary disease, genetic factors that contribute to the development of renal epithelial tumors are unknown. There is a possibility that the MDR1 encoded plasma membrane transporter P-glycoprotein (PGP) influences the risk of development of renal neoplasms. PGP is known to be involved in uptake, binding, transport, and distribution of xe- nobiotics. There is evidence that the MDR1 C3435T polymor- phism drives expression and modulates disease risk. In an explorational case-control study, constitutional genotype fre- quencies were established at MDR1 C3435T of 537 healthy con- trol subjects and compared with those of 212 patients with renal epithelial tumors. There were 179 clear cell renal cell carcinoma (CCRCC) and 33 tumors collectively assigned as non-CCRCC. In a second study, genotypes of another 150 healthy control subjects and 50 patients with three non- CCRCC types (26 papillary RCC, 11 chromophobe RCC, and 13 renal oncocytic adenoma) were compared. PCR-restriction fragment length polymorphism- based analysis of constitu- tional DNA, and statistical analysis were applied. PGP expres- sion was analyzed by quantitative immunohistochemistry. The explorational study showed a significant association between T allele frequency and the occurrence of tumors (P 0.007). When tumors were histopathologically distinguished into fre- quent CCRCC and less frequent non-CCRCC, both patient groups contributed to this effect with a seemingly strong in- fluence by the latter (P 0.0419). The second study estab- lished the T allele as a risk factor especially for non-CCRCC (P 0.0005) with the highest risk for homozygote TT allele