Associations of ABCB1 and XPC Genetic Polymorphisms with Susceptibility to Colorectal Cancer and Therapeutic Prognosis in a Chinese Population

Abstract

Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC)as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performedon the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospitalbased,age and sex frequency-matched controls using polymerase chain reaction-restriction fragment lengthpolymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantlylinked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjustedOR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC ACgenotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated witha tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/Avariant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients(n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found withPFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated thatABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility,but not for prognosis with oxaliplatin chemosensitivity in CRC patients.

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