Calpain-10 SNP43 and SNP19 Polymorphisms and Colorectal Cancer: a Matched Case-control Study

Abstract

Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/ Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk.

Development and Validation of an Autophagy Score Signature for the Prediction of Post-operative Survival in Colorectal Cancer

“…Some scientists identified that the calpain-10 (CAPN10) gene is the first candidate type 2 diabetes mellitus (T2DM) gene, which is associated with decreased glucose tolerance and insulin resistance (IR) phenotypes by genome-wide linkage and positional cloning. Previous studies suggested that CAPN10 is important for IR, which is relevant to CRC risk (23). Consequently, results from foregoing study also support our hypothesis that, for patients whose expression level of CAPN10 is low and clinicopathological characteristics are comparable, survival chances are higher.…”

C1222C Deletion in Exon 8 of ABL1 Is Involved in Carcinogenesis and Cell Cycle Control of Colorectal Cancer Through IRS1/PI3K/Akt Pathway

“…Moreover, the mutation of ABL1 was also elevated in CRC patients. Based on the results from previous studies, the mutation rate of the ABL1 gene is relatively higher in men than in women patients with CRC worldwide (3,23). In a previous study, the ABL1 gene was found to be mutated in 0.9% of patients with CRC at Sir Ganga Ram Hospital, Delhi, India (5).…”

Insulin Resistance Reduces Sensitivity to Cis-Platinum and Promotes Adhesion, Migration and Invasion in HepG2 Cells

“…Glucose metabolism dysregulation is a feature of malignant cancer that results in decreased insulin sensitivity and IR. IR is a high risk factor for multiple cancers (Hu et al, 2013). The prevention of IR represents one of the most important strategies to reduce the risk of postoperative recurrence.…”