[Application of multifactor dimensionality reduction on the interactions between gene-gene, gene-environment and the risk sporadic colorectal cancer in Chinese population].
OBJECTIVE
To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors.


METHODS
In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown. Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis.


RESULTS
As compared to the younger age group (> or = 42, < 61 years), the risk of colorectal cancer in older age group (> or = 61 years) increased significantly (OR = 2.04, 95% CI: 1.49-2.80). Similar result was observed in the family cancer history (OR = 1.51, 95% CI: 1.05-2.17). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0.616, P = 0.011). Using a logistic regression model, the "high-risk" individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model (OR = 2.72, 95% CI: 1.66-4.47).


CONCLUSIONS
The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.
Jin
Ming-Juan
MJ
Department of Epidemiology and Health Statistics, Zhejiang University School of Medicine, Hangzhou 310058, China.
Liu
Bing
B
Zhang
Shuang-Shuang
SS
Zhang
Yong-Jing
YJ
Xu
Mei
M
Ma
Xin-Yuan
XY
Yao
Kai-Yan
KY
Chen
Kun
K
D000328:Adult; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004260:DNA Repair; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors