GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

Abstract

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of colorectal cancer (CRC). However, whether these loci affect clinical outcomes of CRC is not clear. In this study, we genotyped 26 single nucleotide polymorphisms (SNPs) in 10 GWAS-identified CRC susceptibility regions and evaluated their associations with survival and recurrence in 285 stage II and III patients receiving fluorouracil-based adjuvant chemotherapy. Only one SNP, rs10318 (15q13.3), was significantly associated with recurrence for patients with stage II disease. Three SNPs: rs10749971 (11q23.1), rs961253 (20p12.3) and rs355527 (20p12.3) in two regions were significantly associated with recurrence for patients with stage III disease. Five SNPs: rs961253 (20p12.3), rs355527 (20p12.3), rs4464148 (18q21.1), rs6983267 (8q24.21) and rs10505477 (8q24.21) in three regions were significantly associated with survival for patients with stage III disease. Cumulative effects of multiple unfavorable genotypes were observed for recurrence and survival in patients with stage III CRC. Our results suggest that cancer susceptibility loci may also affect the prognosis of CRC patients receiving fluorouracil-based adjuvant chemotherapy.

Fig. 1.

Kaplan–Meier curves of stage III CRC patients who received 5-FU-based adjuvant chemotherapy stratified by the number of unfavorable genotypes. (A) Overall survival; (B) recurrence-free survival.