Hu Xiao-Qin, Yuan Ping, Luan Rong-Sheng, Li Xiao-Ling, Liu Wen-Hui, Feng Fei, Yan Jin, Yang Yan-Fang
Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China E-mail :
Asian Pac J Cancer Prev. 2014 Jan;14(11):6673-80. doi: 10.7314/apjcp.2013.14.11.6673.
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.
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.
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.
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.
胰岛素抵抗（IR）是结直肠癌（CRC）已确定的危险因素。鉴于CRC与IR在生理上存在重叠，且钙蛋白酶-10基因（CAPN10）是IR的候选基因，我们探讨了CAPN10与CRC风险之间的关联。
对400对病例对照的血样进行基因分型，并记录和收集这些对照的生活方式和饮食习惯。采用无条件逻辑回归（LR）评估CAPN10 SNP43和SNP19以及环境因素的影响。使用广义多因素降维法（GMDR）和分类回归树（CART）来检验CRC风险的基因-环境相互作用。
SNP43的GA+AA基因型和SNP19的Del/Ins+Ins/Ins基因型与CRC风险存在微弱关联（GA+AA：比值比=1.35，95%置信区间=0.92-1.99；Del/Ins+Ins/Ins：比值比=1.31，95%置信区间=0.84-2.04）。值得注意的是，GMDR和CART分析一致识别出一种高阶相互作用。在GMDR中，SNP43、SNP19、红肉消费和烟熏肉消费的四因素相互作用模型是最佳模型，最大交叉验证一致性为10/10，检验平衡准确率为0.61（P<0.01）。在LR中，红肉和烟熏肉高消费且具有两种风险基因型的受试者患CRC的风险是红肉和烟熏肉低消费且无风险基因型受试者的6.17倍（95%置信区间=2.44-15.6）。在CART中，红肉和烟熏肉高消费、SNP19 Del/Ins+Ins/Ins以及SNP43 GA+AA的个体患CRC的风险（比值比=4.56，95%置信区间=1.94-10.75）高于红肉和烟熏肉低消费的个体。
虽然CAPN10 SNP43和SNP19的单个位点不足以显著增加CRC易感性，但SNP43、SNP19、红肉消费和烟熏肉消费的组合与风险升高相关。
