Genes in the insulin and insulin-like growth factor pathway and odds of metachronous colorectal neoplasia

Abstract

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.

Risk factors for metachronous colorectal cancer or polyp: A systematic review and meta‐analysis

“…A manual search of reference lists captured nine further studies that met our entry criteria . Thus, 55 studies published between 1987 and 2016 were included in the review (Tables and ) …”

Association between Polymorphisms of Insulin and Insulin Receptor Gene with Childhood Obesity in Malay Population

“…To the best of our knowledge, our study is the first to assess the association of INSR polymorphisms with childhood obesity. Previously, studies on association of INSR gene polymorphisms with hypertension (Kuo et al (LeRoy et al 2011;Cox et al 2009;Wang et al 2007) and type 2 diabetes (Bodhini et al 2012) have been reported but not with obesity. Insulin signalling plays a crucial role in lipid storage and regulation of glucose homeostasis in adipose tissue (Blüher et al 2002).…”

The association between IGF1 gene rs1520220 polymorphism and cancer susceptibility: a meta-analysis based on 12,884 cases and 58,304 controls

“…Thus far, with the improvement of living standards in more and more developing countries, obesity and lifestyle-related cancers have been on the increase [ 33 , 34 ]. IGF1 has been reported to relate to be associated with the cancer susceptibility, especially cancers caused by obesity, due to its important role in cell proliferation [ 35 ].…”