Polymorphism of the insulin gene is associated with increased prostate cancer risk

Abstract

High insulin levels are linked with increased cancer risk, including prostate cancer. We examined the associations between prostate cancer with polymorphisms of the insulin gene (INS) and its neighbouring genes, tyrosine-hydroxylase and IGF-II (TH and IGF2). In this study, 126 case -control pairs matched on age, race, and countries of origin were genotyped for +1127 INS-PstI in INS, -4217 TH-PstI in TH, and +3580 IGF2-MspI in IGF2. The homozygous CC genotype of +1127 INS-PstI occurred in over 60% of the population. It was associated with an increased risk of prostate cancer in nondiabetic Blacks and Caucasians (OR ¼ 3.14, P ¼ 0.008). The CC genotype was also associated with a low Gleason score o7 (OR ¼ 2.60, P ¼ 0.022) and a late age of diagnosis (OR ¼ 2.10, P ¼ 0.046). Markers in the neighbouring genes of INS showed only null to modest associations with prostate cancer. The polymorphism of INS may play a role in the aetiology of prostate cancer. Given the high prevalence of the CC genotype and its association with late age of onset of low-grade tumours, this polymorphism may contribute to the unique characteristics of prostate cancer, namely a high prevalence of indolent cancers and the dramatic increase in incidence with age.

Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect

“…We confirmed high LD in the INS gene and selected the C1127INSPstI SNP (rs3842752) for further analysis because it has been previously used as a surrogate for the functional VNTR polymorphism in studies of diseases related to insulin resistance, including cancer (Ho et al 2003, Claeys et al 2005, Li et al 2005, Neuhausen et al 2005. In the IGFBPI gene, the only non-synonymous SNP Ile253Met (rs4619) was in 100% LD with all the other SNPs along the entire IGFBPI gene region as previously shown by Cheng et al (2006) and therefore, we selected it for further analysis.…”

“…Tight linkage disequilibrium (LD) has been reported between several single nucleotide polymorphisms (SNPs) and the VNTR (Bennett & Todd 1996). Several groups have studied the relationship between prostate cancer and one of the linked SNPs, C1127INSPstI, with inconsistent results (Ho et al 2003, Claeys et al 2005, Li et al 2005, Neuhausen et al 2005.…”

“…So far, prostate cancer is the most intensively studied cancer with regard to the effect of polymorphisms in the INS, IRS1, IRS2, and IGFBPI genes on cancer susceptibility (Ho et al 2003, Claeys et al 2005, Li et al 2005, Neuhausen et al 2005, Stephens et al 2005, Cheng et al 2006. Only one study has focused on IRS1 and IRS2 polymorphisms and the risk of CRC (Slattery et al 2004).…”

Is there an Association between Variants in Candidate Insulin Pathway Genes IGF-I, IGFBP-3, INSR, and IRS2 and Risk of Colorectal Cancer in the Iranian Population?

“…Some previous studies conducted to investigate the effect of IGF-I, INSR and IRS2 gene polymorphisms on insulin resistant and type 2 diabetes mellitus (FloresMartínez et al, 2004;Bodhini et al, 2007;Vella et al, 2008;Baroudi Ouederni et al, 2009;Malodobra et al, 2011). So far, the associations of insulin pathway gene polymorphisms with prostate and breast cancer have been studied intensively but their results were inconsistent (Ho et al, 2003;Neuhausen et al, 2005;Deming et al, 2007;Deming et al, 2008;Sarma et al, 2008;Xuefen et al, 2010). Only a few studies have focused on variants in genes along the insulin pathway regarded to their effect on the risk of CRC .…”

ProstaCaid™ inhibits tumor growth in a xenograft model of human prostate cancer

“…Furthermore, polymorphism of the IGF2 gene and aging related epigenetic alteration such as loss of imprinting (LOI) for IGF2 is associated with increased prostate cancer risk (31,32). Importantly, epigenetic inhibition of IGF2 expression suppressed hepatocellular carcinoma growth in nude mice (33), and a targeted gene therapy based on loss of IGF2 imprinting suppressed growth of colon tumor xenografts in vivo (34).…”