NDLI: Insulin receptor variants and obesity-related cancers in the Framingham Heart Study

Content Provider	Springer Nature Link
Author	Parekh, Niyati Guffanti, Guia Lin, Yong Ochs Balcom, Heather M. Makarem, ur Hayes, Richard
Copyright Year	2015
Abstract	The insulin-signaling pathway plays a pivotal role in cancer biology; however, evidence of genetic alterations in human studies is limited. This case–control study nested within the Framingham Heart Study (FHS) examined the association between inherited genetic variation in the insulin receptor (INSR) gene and obesity-related cancer risk.The study sample consisted of 1,475 controls and 396 cases from the second familial generation of the FHS. Participants who provided consent were genotyped. Nineteen single-nucleotide polymorphisms (SNPs) in the INSR gene were investigated in relation to risk of obesity-related cancers combined and breast, prostate and colorectal cancers. Generalized estimation equation models controlling for familial correlations and include age, sex, smoking and body mass index as covariates, assuming additive models, were used.Three SNPs, rs2059807, s8109559 and rs919275, were significantly associated with obesity-related cancers (p value < 0.02) with the most significantly associated SNP being rs2059807 (p value = 0.008). Carriers of two copies of SNP rs2059807 risk allele T were significantly less prevalent among subjects with obesity-related cancers [f(TT)cases = 14 vs. f(TT)controls = 18 %; OR 1.23]. In exploratory analyses evaluating site-specific cancers, the INSR rs2059807 association with these cancers was consistent with that observed for the main outcome (ORs colorectal cancer = 1.5, breast cancer = 1.29, prostate = 1.06). There was no statistically significant interaction between the INSR–SNP and blood glucose in relation to obesity-related cancer.The INSR gene is implicated in obesity-related cancer risk, as 3 of 19 SNPs were nominally associated, after false discovery rate (FDR) correction, with the main outcome. Risk allele homozygotes (rs2059807) were less prevalent among subjects with obesity-related cancer. These results should be replicated in other populations to confirm the findings.
Starting Page	1189
Ending Page	1195
Page Count	7
File Format	PDF
ISSN	09575243
Journal	Cancer Causes & Control
Volume Number	26
Issue Number	8
e-ISSN	15737225
Language	English
Publisher	Springer International Publishing
Publisher Date	2015-06-16
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Genetic polymorphisms INSR gene Insulin-signaling pathway Cancer Framingham Heart Study Cancer Research Biomedicine general Oncology Public Health Epidemiology Hematology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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