title: Susceptibility variants for obesity and colorectal cancer risk: the multiethnic cohort and PAGE studies.
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.
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA. ulim@cc.hawaii.edu
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Christian
authors.initials: C
authors.lastname: Caberto
authors.forename: Maarit
authors.initials: M
authors.lastname: Tiirikainen
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Sungshim Lani
authors.initials: SL
authors.lastname: Park
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012306:Risk
chemical_list: C552182:KCTD15 protein, human; D015221:Potassium Channels; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human