title: Genetic variants of adiponectin and risk of colorectal cancer.
abstract: Circulating adiponectin has been associated with lower risk of colorectal cancer (CRC). Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with adiponectin levels. However, it is unclear whether these SNPs are associated with CRC risk. In addition, previous data on SNPs in the adiponectin pathway and their associations with CRC are inconsistent. Therefore, we examined 19 SNPs in genes related to adiponectin or its receptors and their associations with CRC using logistic regression among 7,020 cases and 7,631 controls drawn from ten studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium. Using data from a subset of two large cohort studies, we also assessed the contribution of individual SNPs and an adiponectin genetic score to plasma adiponectin after accounting for lifestyle factors among 2,217 women and 619 men. We did not find any statistically significant association between the 19 adiponectin-associated SNPs and CRC risk (multivariable-adjusted odds ratios ranged from 0.89 to 1.05, all p > 0.05). Each SNP explained less than 2.50% of the variance of plasma adiponectin, and the genetic score collectively accounted for 2.95 and 1.42% of the variability of adiponectin in women and men, respectively, after adjustment for age, body mass index, physical activity, smoking, alcohol consumption, regular use of aspirin or nonsteroidal anti-inflammatory drug and postmenopausal hormone use. In conclusion, our findings do not support an association between known adiponectin-related common SNPs and CRC incidence. However, known common SNPs account for only a limited proportion of the interindividual variance in circulating adiponectin. Further work is warranted to investigate the relationship between adiponectin and CRC while accounting for other components in the pathway.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Song
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Keith R
authors.initials: KR
authors.lastname: Curtis
authors.forename: Tabitha A
authors.initials: TA
authors.lastname: Harrison
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Shuo
authors.initials: S
authors.lastname: Jiao
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Eric
authors.initials: E
authors.lastname: Rimm
authors.forename: Majken
authors.initials: M
authors.lastname: Jensen
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin
keywords: Mendelian randomization; adiponectin; colorectal cancer; lifestyle factors; single-nucleotide polymorphism