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.
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 CRCpatients underwent curative surgery and then genotyped for 5 polymorphisms (PPP1R13Lrs1970764 and rs1005165; CD3EAPrs967591; ERCC1rs735482 and rs11615) using PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Among the 5 polymorphisms, PPP1R13Lrs1970764 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 PPP1R13Lrs1970764 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 PPP1R13Lrs1970764 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 PPP1R13Lrs1970764 variant is a possible prognostic marker for patients with rectal cancer.
Authors: Jiaoyang Yin; Eszter Rockenbauer; Mohammad Hedayati; Nicklas Raun Jacobsen; Ulla Vogel; Lawrence Grossman; Lars Bolund; Børn A Nexø Journal: Cancer Epidemiol Biomarkers Prev Date: 2002-11 Impact factor: 4.254
Authors: Ken A Olaussen; Ariane Dunant; Pierre Fouret; Elisabeth Brambilla; Fabrice André; Vincent Haddad; Estelle Taranchon; Martin Filipits; Robert Pirker; Helmut H Popper; Rolf Stahel; Laure Sabatier; Jean-Pierre Pignon; Thomas Tursz; Thierry Le Chevalier; Jean-Charles Soria Journal: N Engl J Med Date: 2006-09-07 Impact factor: 91.245
Authors: Daniel T Chang; Rish K Pai; Lisa A Rybicki; Michael A Dimaio; Maneesha Limaye; Priya Jayachandran; Albert C Koong; Pamela A Kunz; George A Fisher; James M Ford; Mark Welton; Andrew Shelton; Lisa Ma; Daniel A Arber; Reetesh K Pai Journal: Mod Pathol Date: 2012-04-06 Impact factor: 7.842
Authors: Daniele Bergamaschi; Milena Gasco; Louise Hiller; Alexandra Sullivan; Nelofer Syed; Giuseppe Trigiante; Isik Yulug; Marco Merlano; Gianmauro Numico; Alberto Comino; Marlene Attard; Olivier Reelfs; Barry Gusterson; Alexandra K Bell; Victoria Heath; Mahvash Tavassoli; Paul J Farrell; Paul Smith; Xin Lu; Tim Crook Journal: Cancer Cell Date: 2003-04 Impact factor: 31.743