INTRODUCTION: Insulin, insulin-like growth factor (IGF), and IGF binding protein (IGFBP) are involved in cell growth and proliferation and are thought to be important in the etiology of colorectal cancer. We hypothesize that genetic polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP-3 alter colorectal cancer risk because of their roles in the insulin-related signaling pathway. METHODS: Data from a population-based incident case-control study of 1,346 colon cancer cases and 1,544 population-based controls and 952 rectal cancer cases and 1,205 controls were used to evaluate associations. Genetic polymorphisms of four genes were investigated: an IGF1 CA repeat, the IGFBP3 -202 A > C, the IRS1 G972R, and the IRS2 G1057D. RESULTS: Having at least one R allele (GR or RR) for IRS1 G972R was associated with an increased risk of colon cancer [odds ratio 1.4, 95% confidence interval (95% CI) 1.1-1.9]. The IRS2 G972R heterozygote GD genotype significantly reduced risk of colon cancer (odds ratio 0.8, 95% CI 0.6-0.9). Neither the IGF1 nor the IGFBP3 variants was associated independently with colon cancer, but there was an association when examined with IRS1. Individuals with an IRS1 R allele and IGF1 non-192 allele were at a 2-fold increased risk of colon cancer (95% CI 1.2-4.4). There was a 70% (95% CI 1.02-2.8) increased risk of colon cancer with an IRS1 R allele and the IGFBP3 AC or CC genotype. The IRS2 GD genotype reduced risk of colon cancer, except among those with an IRS1 R allele. No significant associations were seen in analyses of main effects or interactions of these variants and rectal cancer risk. CONCLUSIONS: Both IRS1 and IRS2 variants were associated with colon cancer risk independently. Associations were slightly stronger when polymorphisms in multiple genes were evaluated in conjunction with other genes rather than individually. These data suggest that the insulin-related pathway may be important in the etiology of colon cancer but not rectal cancer.
INTRODUCTION:Insulin, insulin-like growth factor (IGF), and IGF binding protein (IGFBP) are involved in cell growth and proliferation and are thought to be important in the etiology of colorectal cancer. We hypothesize that genetic polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP-3 alter colorectal cancer risk because of their roles in the insulin-related signaling pathway. METHODS: Data from a population-based incident case-control study of 1,346 colon cancer cases and 1,544 population-based controls and 952 rectal cancer cases and 1,205 controls were used to evaluate associations. Genetic polymorphisms of four genes were investigated: an IGF1 CA repeat, the IGFBP3 -202 A > C, the IRS1G972R, and the IRS2G1057D. RESULTS: Having at least one R allele (GR or RR) for IRS1G972R was associated with an increased risk of colon cancer [odds ratio 1.4, 95% confidence interval (95% CI) 1.1-1.9]. The IRS2G972R heterozygote GD genotype significantly reduced risk of colon cancer (odds ratio 0.8, 95% CI 0.6-0.9). Neither the IGF1 nor the IGFBP3 variants was associated independently with colon cancer, but there was an association when examined with IRS1. Individuals with an IRS1 R allele and IGF1 non-192 allele were at a 2-fold increased risk of colon cancer (95% CI 1.2-4.4). There was a 70% (95% CI 1.02-2.8) increased risk of colon cancer with an IRS1 R allele and the IGFBP3 AC or CC genotype. The IRS2 GD genotype reduced risk of colon cancer, except among those with an IRS1 R allele. No significant associations were seen in analyses of main effects or interactions of these variants and rectal cancer risk. CONCLUSIONS: Both IRS1 and IRS2 variants were associated with colon cancer risk independently. Associations were slightly stronger when polymorphisms in multiple genes were evaluated in conjunction with other genes rather than individually. These data suggest that the insulin-related pathway may be important in the etiology of colon cancer but not rectal cancer.
Authors: A Joan Levine; Ugonna Ihenacho; Won Lee; Jane C Figueiredo; David J Vandenberg; Christopher K Edlund; Brian D Davis; Mariana C Stern; Robert W Haile Journal: Int J Colorectal Dis Date: 2012-05-30 Impact factor: 2.571
Authors: Martha L Slattery; Roger K Wolff; Karen Curtin; Frank Fitzpatrick; Jennifer Herrick; John D Potter; Bette J Caan; Wade S Samowitz Journal: Mutat Res Date: 2008-10-15 Impact factor: 2.433
Authors: Michela Padovani; Jackie A Lavigne; Gadisetti V R Chandramouli; Susan N Perkins; J Carl Barrett; Stephen D Hursting; L Michelle Bennett; David Berrigan Journal: Cancer Prev Res (Phila) Date: 2009-12-01
Authors: Akiko Hanyuda; Sun A Kim; Alejandro Martinez-Fernandez; Zhi Rong Qian; Mai Yamauchi; Reiko Nishihara; Teppei Morikawa; Xiaoyun Liao; Kentaro Inamura; Kosuke Mima; Yin Cao; Xuehong Zhang; Kana Wu; Andrew T Chan; Edward L Giovannucci; Jeffrey A Meyerhardt; Charles S Fuchs; Ramesh A Shivdasani; Shuji Ogino Journal: Ann Surg Oncol Date: 2015-11-17 Impact factor: 5.344
Authors: Guido T Bommer; Ying Feng; Ayaka Iura; Thomas J Giordano; Rork Kuick; Hüseyin Kadikoy; Deanna Sikorski; Rong Wu; Kathleen R Cho; Eric R Fearon Journal: J Biol Chem Date: 2009-10-20 Impact factor: 5.157