caa a22 4500 445861851 CHVBK 20180317145446.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00439-010-0942-0 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0942-0 Genes in the insulin and insulin-like growth factor pathway and odds of metachronous colorectal neoplasia [Elektronische Daten] [Elizabeth LeRoy, Jason Moore, Chengcheng Hu, María Martínez, Peter Lance, David Duggan, Patricia Thompson] Insulin and insulin-like growth factor (IGF) genes are implicated in colorectal carcinogenesis. Gene-by-gene interactions that influence the insulin/IGF pathways were hypothesized as modifiers of colorectal neoplasia risk. We built a classification tree to detect interactions in 18 IGF and insulin pathway-related genes and metachronous colorectal neoplasia among 1,439 subjects pooled from two chemoprevention trials. The probability of colorectal neoplasia was greatest (71.8%) among carriers of any A allele for rs7166348 (IGF1R) and AA genotype for rs1823023 (PIK3R1). In contrast, carriers of any A at rs7166348 (IGF1R), any G for the PIK3R1 variant, and AA for rs10426094 (INSR) had the lowest probability (14.3%). Logistic regression modeling showed that any A at rs7166348 (IGF1R) with the AA genotype at rs1823023 (PIK3R1) conferred the highest odds of colorectal neoplasia (OR 3.7; 95% CI 2.2-6.5), compared with carriage of GG at rs7166348 (IGF1R). Conversely, any A at rs7166348 (IGFR1), any G allele at rs1823023 (PIK3R1), and the AA genotype at rs10426094 (INSR) conferred the lowest odds (OR 0.22; 95% CI 0.07-0.66). Stratifying the analysis by parent study and intervention arm showed highly consistent trends in direction and magnitude of associations, with preliminary evidence of genotype effects on measured IGF-1 levels in a subgroup of subjects. These results were compared to those from multifactor dimensionality reduction, which identified different single nucleotide polymorphisms in the same genes (INSR and IGF1R) as effect modifiers for colorectal neoplasia. These results support a role for genetic interactions in the insulin/IGF pathway genes in colorectal neoplasia risk. Springer-Verlag, 2011 LeRoy Elizabeth Arizona Cancer Center, University of Arizona, Tucson, AZ, USA aut Moore Jason Computational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, NH, USA aut Hu Chengcheng Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut Martínez María Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut Lance Peter Arizona Cancer Center, University of Arizona, Tucson, AZ, USA aut Duggan David Translational Genomic Research Institute, Phoenix, AZ, USA aut Thompson Patricia Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut Human Genetics Springer-Verlag 129/5(2011-05-01), 503-512 0340-6717 129:5<503 2011 129 439 https://doi.org/10.1007/s00439-010-0942-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0942-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- LeRoy Elizabeth Arizona Cancer Center, University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Moore Jason Computational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, NH, USA aut NATIONALLICENCE 700 1- Hu Chengcheng Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Martínez María Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Lance Peter Arizona Cancer Center, University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Duggan David Translational Genomic Research Institute, Phoenix, AZ, USA aut NATIONALLICENCE 700 1- Thompson Patricia Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/5(2011-05-01), 503-512 0340-6717 129:5<503 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer