PURPOSE: Extensive evidence has suggested that risk factors of cancer development may also modulate cancer clinical outcome. Recent genome-wide association (GWA) studies identified several single nucleotide polymorphisms (SNPs) predisposing to colorectal cancer (CRC). Given the pivotal importance of these variants in CRC, we sought to evaluate their associations with clinical outcomes of the disease. EXPERIMENTAL DESIGN: In a well-characterised cohort including 380 Chinese CRC patients, we genotyped seven SNPs identified in previous multi-stage GWA studies and analysed their associations with patient recurrence and survival. RESULTS: One SNP on chromosome 15q13, rs4779584 was associated with reduced risk of death with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.15-0.72, P = 0.007). Another SNP in a gene-desert region on chromosome 10p14, rs10795668, was associated with a reduced risk of recurrence with an HR of 0.55 (95% CI 0.30-1.00, P = 0.05). In a stratified analysis, this association was only evident in patients receiving chemotherapy (HR = 0.32, 95% CI 0.14-0.78, P = 0.01, log rank P = 0.004), but not in those without chemotherapy (HR = 1.08, 95% CI 0.43-2.73, P = 0.87, log rank P = 0.66). Moreover, we found that the effects of chemotherapy on CRC recurrence was only evident in patients with the variant-containing genotypes (HR = 0.35, 95% CI 0.13-0.94, P = 0.04) but not in those with the wild-type genotype of rs10795668. Further analyses indicated a borderline significant interaction effect (P interaction = 0.05) between rs10795668 and chemotherapy on patient recurrence. CONCLUSIONS: Our data suggested that rs10795668, a CRC susceptibility variant identified by GWA studies, might be used as a biomarker to identify CRC patients with high risk of recurrence after chemotherapy.
PURPOSE: Extensive evidence has suggested that risk factors of cancer development may also modulate cancer clinical outcome. Recent genome-wide association (GWA) studies identified several single nucleotide polymorphisms (SNPs) predisposing to colorectal cancer (CRC). Given the pivotal importance of these variants in CRC, we sought to evaluate their associations with clinical outcomes of the disease. EXPERIMENTAL DESIGN: In a well-characterised cohort including 380 Chinese CRC patients, we genotyped seven SNPs identified in previous multi-stage GWA studies and analysed their associations with patient recurrence and survival. RESULTS: One SNP on chromosome 15q13, rs4779584 was associated with reduced risk of death with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.15-0.72, P = 0.007). Another SNP in a gene-desert region on chromosome 10p14, rs10795668, was associated with a reduced risk of recurrence with an HR of 0.55 (95% CI 0.30-1.00, P = 0.05). In a stratified analysis, this association was only evident in patients receiving chemotherapy (HR = 0.32, 95% CI 0.14-0.78, P = 0.01, log rank P = 0.004), but not in those without chemotherapy (HR = 1.08, 95% CI 0.43-2.73, P = 0.87, log rank P = 0.66). Moreover, we found that the effects of chemotherapy on CRC recurrence was only evident in patients with the variant-containing genotypes (HR = 0.35, 95% CI 0.13-0.94, P = 0.04) but not in those with the wild-type genotype of rs10795668. Further analyses indicated a borderline significant interaction effect (P interaction = 0.05) between rs10795668 and chemotherapy on patient recurrence. CONCLUSIONS: Our data suggested that rs10795668, a CRC susceptibility variant identified by GWA studies, might be used as a biomarker to identify CRC patients with high risk of recurrence after chemotherapy.
Authors: Amanda I Phipps; Michael N Passarelli; Andrew T Chan; Tabitha A Harrison; Jihyoun Jeon; Carolyn M Hutter; Sonja I Berndt; Hermann Brenner; Bette J Caan; Peter T Campbell; Jenny Chang-Claude; Stephen J Chanock; Jeremy P Cheadle; Keith R Curtis; David Duggan; David Fisher; Charles S Fuchs; Manish Gala; Edward L Giovannucci; Richard B Hayes; Michael Hoffmeister; Li Hsu; Eric J Jacobs; Lina Jansen; Richard Kaplan; Elisabeth J Kap; Timothy S Maughan; John D Potter; Robert E Schoen; Daniela Seminara; Martha L Slattery; Hannah West; Emily White; Ulrike Peters; Polly A Newcomb Journal: Carcinogenesis Date: 2015-11-19 Impact factor: 4.944
Authors: Amanda I Phipps; Polly A Newcomb; Xabier Garcia-Albeniz; Carolyn M Hutter; Emily White; Charles S Fuchs; Aditi Hazra; Shuji Ogino; Hongmei Nan; Jing Ma; Peter T Campbell; Jane C Figueiredo; Ulrike Peters; Andrew T Chan Journal: Gastroenterology Date: 2012-05-08 Impact factor: 22.682