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Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions
Author(s) -
Slattery Martha L.,
Wolff Roger K.,
Herrick Jennifer,
Caan Bette J.,
Potter John D.
Publication year - 2008
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.23135
Subject(s) - leptin , igfbp3 , leptin receptor , medicine , endocrinology , genotype , colorectal cancer , insulin , insulin like growth factor , biology , calcitriol receptor , insulin receptor , cancer , vitamin d and neurology , receptor , insulin resistance , obesity , genetics , gene , growth factor
Leptin may play an important role in colorectal cancer because of its role in energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G > A) and rs7799039 (−2548 G > A) polymorphisms and the leptin receptor, LEPR rs6588147 (located in intron 2), polymorphism with risk of developing colon cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and genetic variations in genes related to insulin signaling pathways including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 3 (IGFBP3), and insulin‐related substrates 1 and 2 (IRS1, IRS2) and the vitamin D receptor (VDR). We observed a slight reduction in colon cancer risk with the AA LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching statistical significance, with the combined GG LEP rs2167270 and GG LEPR rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID use significantly interacted with both LEP polymorphisms. Likewise, variants of IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance. © 2007 Wiley‐Liss, Inc.