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Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population.
Indian J Hum Genet ; 2012 Jan; 18(1): 47-55
Article in English | IMSEAR | ID: sea-139442
ABSTRACT

BACKGROUND:

Inherited polymorphisms of XPD and XPC genes may contribute to subtle variations in NER DNA repair capacity and genetic susceptibility to development of urological cancer such as prostate and bladder cancer. MATERIALS AND

METHODS:

We genotyped four Single Nucleotide Polymorphs (SNPs) of the DNA repair gene XPD and XPC in 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 healthy controls from the same area. XPD Exon 10 (G>A) by amplification refractory mutation system and Exon 23 (A>C), XPC Intron 9 (Ins/Del) and Exon 15 (A>C) were genotyped by PCR-RFLP.

RESULTS:

Variant genotype of XPC demonstrated association with PCa as well as in BC (P, 0.013; P, 0.003). Combined genotype (GA+AA) revealed association with PCa and in BC (P, 0.012, P, 0.002). Variant allele also demonstrated risk in both the cancer. Diplotype of XPD and XPC was associated with a significant increase in PCa and BC risk. Variant (+/+) genotype of XPC intron 9 shown increased risk with PCa and in BC (P, 0.012; P, 0.032). CC genotype of XPC exon 15 revealed increase risk (P, 0.047) with PCa not in BC. In clinopathological grade variant allele of XPC intron 9 and 15 demonstrated risk with high grade of tumor and bone metastasis of PCa. In BC variant allele of XPD exon 10 and 15 also shown association with tumor grade. XPC intron 9 influences the risk of BC in former tobacco users in BC.

CONCLUSIONS:

Our result support that SNPs in XPD and XPC gene may reduce NER repair capacity and play a major role for PCa and BC in North India.
Subject(s)

Full text: Available Index: IMSEAR (South-East Asia) Main subject: Polymorphism, Genetic / Prostatic Neoplasms / Genetic Variation / Urinary Bladder Neoplasms / Aged / Female / Humans / Male / Adult / Polymorphism, Single Nucleotide Country/Region as subject: Asia Language: English Journal: Indian J Hum Genet Year: 2012 Type: Article

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Full text: Available Index: IMSEAR (South-East Asia) Main subject: Polymorphism, Genetic / Prostatic Neoplasms / Genetic Variation / Urinary Bladder Neoplasms / Aged / Female / Humans / Male / Adult / Polymorphism, Single Nucleotide Country/Region as subject: Asia Language: English Journal: Indian J Hum Genet Year: 2012 Type: Article