GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

Jingyao Dai; Jian Gu; Maosheng Huang; Cathy Eng; E. Scott Kopetz; Lee M. Ellis; Ernest Hawk; Xifeng Wu

doi:10.1093/carcin/bgs147

GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

Jingyao Dai, Jian Gu, Maosheng Huang, Cathy Eng, E. Scott Kopetz, Lee M. Ellis, Ernest Hawk, Xifeng Wu

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39 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1327-1331
Number of pages	5
Journal	Carcinogenesis
Volume	33
Issue number	7
DOIs	https://doi.org/10.1093/carcin/bgs147
State	Published - Jul 2012

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgs147

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title = "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.",

author = "Jingyao Dai and Jian Gu and Maosheng Huang and Cathy Eng and Kopetz, {E. Scott} and Ellis, {Lee M.} and Ernest Hawk and Xifeng Wu",

note = "Funding Information: This work was supported by a Multidisciplinary Research Program grant on colorectal cancer from the University of Texas MD Anderson Cancer Center. The study sponsors were not involved in the study design, in the collection, analysis and interpretation of data or in the writing of the manuscript.",

year = "2012",

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doi = "10.1093/carcin/bgs147",

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AU - Dai, Jingyao

AU - Gu, Jian

AU - Huang, Maosheng

AU - Eng, Cathy

AU - Kopetz, E. Scott

AU - Ellis, Lee M.

AU - Hawk, Ernest

AU - Wu, Xifeng

N1 - Funding Information: This work was supported by a Multidisciplinary Research Program grant on colorectal cancer from the University of Texas MD Anderson Cancer Center. The study sponsors were not involved in the study design, in the collection, analysis and interpretation of data or in the writing of the manuscript.

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

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GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

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