Genetic variation in adipokine genes and risk of colorectal cancer.
OBJECTIVE
Obesity has been related to an increased risk of colorectal cancer (CRC). Adipokines produced by the adipose tissue are directly linked to obesity and may thus contribute to the pathogenesis of CRC. We hypothesized that potentially functional polymorphisms in the adipokine genes leptin (LEP), leptin receptor (LEPR), resistin (RETN), and adiponectin (ADIPOQ) may be associated with CRC.


METHODS
We studied the association of four putatively functional single nucleotide polymorphisms (SNPs) with CRC risk using a hospital-based study design with 702 cases and 752 controls from the Czech Republic. We used likelihood ratio tests to select the best model to represent the relationship between genotypes and risk of CRC. Age-adjusted odds ratios (ORs) under the best model were calculated for each SNP. Previous genotyping data on insulin (INS)-related genes were used to explore interactions between genes in obesity- and diabetes-related pathways by using two independent methods, logistic regression, and multifactor-dimensionality reduction.


RESULTS
A trend to associate between the RETN SNP rs1862513 (C-420G) and CRC risk was observed (per allele OR 1.18, 95% confidence interval (0.99-1.40). Statistically, significant interactions were observed between the INS SNP rs3842754 (+1127INSPstI) genotypes and both the LEPR SNP rs1137101 (Q223R) and the ADIPOQ SNP rs266729 (C-11374G) genotypes.


CONCLUSIONS
Our results suggest that variants in the adipokine genes may affect CRC risk in combination with variants in diabetes-related genes.
Pechlivanis
Sonali
S
Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Bermejo
Justo Lorenzo
JL
Pardini
Barbara
B
Naccarati
Alessio
A
Vodickova
Ludmila
L
Novotny
Jan
J
Hemminki
Kari
K
Vodicka
Pavel
P
Försti
Asta
A
D054392:Adipokines / Q000235:genetics*; D052242:Adiponectin / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D052243:Resistin / Q000235:genetics
D054392:Adipokines; D052242:Adiponectin; D020738:Leptin; D054411:Receptors, Leptin; D052243:Resistin