, Volume 139, Issue 3, pp 465-473
Date: 21 Nov 2012

PPP1R13L variant associated with prognosis for patients with rectal cancer

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Abstract

Background

ERCC1, CD3EAP, and PPP1R13L polymorphisms in the chromosomal region 19q13.2-3 have already been shown to have a synergistic effect on apoptosis and DNA repair pathways. Therefore, the aim of this study was to investigate the association between such genetic variants and the prognosis of colorectal cancer (CRC) following curative surgery.

Methods

DNA was extracted from fresh frozen normal tissue from 349 CRC patients underwent curative surgery and then genotyped for 5 polymorphisms (PPP1R13L rs1970764 and rs1005165; CD3EAP rs967591; ERCC1 rs735482 and rs11615) using PCR-restriction fragment length polymorphism (PCR-RFLP).

Results

Among the 5 polymorphisms, PPP1R13L rs1970764 was significantly associated with relapse-free (RFS) and disease-specific survival (DSS) in a recessive model. In haplotype analysis, three haplotypes (TACC, CGAC, and CGAT) were selected for analysis among 6 haplotypes constructed by the PHASE II program using 4 polymorphisms (rs1005165, rs967591, rs735482, and rs11615) in a moderate to strong linkage disequilibrium (LD) (D′ > 0.4), and a significant difference in RFS was observed among patients with these 3 haplotypes. In the multivariate analysis, the GG genotype of PPP1R13L rs1970764 was identified as an independent prognostic factor for poor RFS and DSS (HR = 1.743 and 1.734; P = 0.003 and 0.010, respectively) when compared with the combine AA/AG genotype adjusted to clinicopathologic variables. In particular, the prognostic impact of PPP1R13L rs1970764 was persistent only in patients with rectal cancer (HR = 3.307 and 3.180; both P < 0.001 for RFS and DSS, respectively).

Conclusions

The present results suggest that the PPP1R13L rs1970764 variant is a possible prognostic marker for patients with rectal cancer.

Jong Gwang Kim and Gyu Seog Choi contributed equally to this work as corresponding authors.