APC、K-ras、p53遺傳基因及環境因子與大腸直腸癌之相關

Abstract

Introduction Predictive model for health risk assessment may be required before using genetic markers in combination with environmental risk factors as screening tool for population-based screening for CRC. Aim We conducted a population-based case-control study with two-stage sampling design to quantify the effect of three genetic major genes and environmental factors on occurrence of CRC and small to large adenomatous polyps. The interaction between gene mutations and environmental factors is also assessed. Methods Data used were derived from a community-based screening program in Keelung, Taiwan within which a population-based screening for colorectal neoplasm with fecal occult blood test (FOBT) was conducted between 1999 and 2004. A total of 53,949 participants were enrolled with the ascertainment of 97 colorectal cancer and 589 adenomatous polyps. Of 20,951 participants in 2001, we randomly selected 20 cancers, 83 adenomatous polyps, and 100 controls for stool DNA analysis on three major mutation genes, APC, K-ras, and p53. Information on environmental risk factors was collected from questionnaire. Logistic regression model was used to estimate adjusted odds ratios and their 95% confidence interval with two-stage method for adjusting odds ratio using information from main study. Receiver operating characteristics (ROC) curve was plotted. Results For environmental factors, variables that were related to the risk for developing colorectal neoplasm included alcohol drinking (aOR=1.40, 95% CI: 1.14-1.72), exercise frequency (aOR=0.71, 95% CI: 0.62-0.82), family history of CRC (aOR=2.09, 95% CI: 1.21-3.60), intake of meat (aOR=1.11, 95% CI: 0.87-1.41), intake of seafood (aOR=1.39, 95% CI: 1.09-1.76), intake of milk (aOR=1.10, 95% CI: 0.91-1.34), intake of vegetables (aOR=1.11, 95% CI: 1.01-1.21), and intake of fruits (aOR=0.91, 95% CI: 0.85-0.97). Subject carried with APC gene mutation had 20-fold risk (95%CI: 6.00-69.65) for the development of colorectal neoplasm compared with those in the absence of APC gene mutation. The corresponding adjusted odds ratios were 56.89 (95%CI: 7.45-434.51) for K-ras gene mutation and 62.61 (95%CI: 14.39-269.06) for p53 gene mutation. Those who were carried with either three of gene mutations had 94-fold risk for colorectal neoplasm compares with those in the absence of these gene mutations. Only the interaction between intake of fruit and APC gene was statistically significant. Information on three mutation genes in combination with environmental factors such as intake of fruit and alcohol drinking has been demonstrated to have a good discriminative ability to predict colorectal neoplasm. Conclusions The impact of environmental factors and three major genes on the risk for developing colorectal neoplasm have been demonstrated. High consumption of meat and alcohol, less intake of fruit, and physical inactivity may increase the risk for developing colorectal neoplasm. APC, K-ras, and P53 are strong predictor for occurrence of colorectal neoplasm. Information from both finding can be used as a screening tool for population-based screening for colorectal neoplasm.