title: 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.
authors.affiliation: Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China E-mail : yang2009@scu.edu.cn.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Rong-Sheng
authors.initials: RS
authors.lastname: Luan
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D005247:Feeding Behavior; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D004247:DNA; D002154:Calpain; C415197:calpain 10