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Susceptibility variants for obesity and colorectal cancer risk: The multiethnic cohort and PAGE studies
Author(s) -
Lim Unhee,
Wilkens Lynne R.,
Monroe Kristine R.,
Caberto Christian,
Tiirikainen Maarit,
Cheng Iona,
Park Sungshim Lani,
Stram Daniel O.,
Henderson Brian E.,
Kolonel Laurence N.,
Haiman Christopher A.,
Le Marchand Loïc
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27592
Subject(s) - medicine , odds ratio , colorectal cancer , body mass index , obesity , single nucleotide polymorphism , oncology , genome wide association study , cohort , cancer , genetics , genotype , biology , gene
Abstract Obesity is a leading contributor to colorectal cancer risk. We investigated whether the risk variants identified in genome‐wide association studies of body mass index (BMI) and waist size are associated with colorectal cancer risk, independently of the effect of obesity phenotype due to a shared etiology. Twenty‐four single nucleotide polymorphisms (SNPs) in 15 loci ( BDNF , FAIM2 , FTO , GNPDA2 , KCTD15 , LYPLAL1 , MC4R , MSRA , MTCH2 , NEGR1 , NRXN3 , SEC16B , SH2B1 , TFAP2B and TMEM18 ) were genotyped in a case–control study of 2,033 colorectal cancer cases and 9,640 controls nested within the multiethnic cohort study, as part of the population architecture using genomics and epidemiology consortium. Risk alleles for two obesity SNPs were associated with colorectal cancer risk— KCTD15 rs29941 [odds ratio (OR) for C allele = 0.90, 95% confidence interval (CI) 0.83–0.98; p = 0.01] and MC4R rs17782313 (OR for C allele = 1.12, 95% CI 1.02–1.22; p = 0.02). These associations were independent of the effect of BMI. However, none of the results remained significant after adjustment for multiple comparisons. No heterogeneity was observed across race/ethnic groups. Our findings suggest that the obesity risk variants are not likely to affect the risk of colorectal cancer substantially.