Application of Crossover Analysis-logistic Regression in the Assessment of Gene- environmental Interactions for Colorectal Cancer.
BACKGROUND
Analysis of gene-gene and gene-environment interactions for complex multifactorial human disease faces challenges regarding statistical methodology. One major difficulty is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures. Based on our previous case-control study in Chongqing of China, we have found increased risk of colorectal cancer exists in individuals carrying a novel homozygous TT at locus rs1329149 and known homozygous AA at locus rs671.


METHODS
In this study, we proposed statistical method- crossover analysis in combination with logistic regression model, to further analyze our data and focus on assessing gene-environmental interactions for colorectal cancer.


RESULTS
The results of the crossover analysis showed that there are possible multiplicative interactions between loci rs671 and rs1329149 with alcohol consumption. Multi- factorial logistic regression analysis also validated that loci rs671 and rs1329149 both exhibited a multiplicative interaction with alcohol consumption. Moreover, we also found additive interactions between any pair of two factors (among the four risk factors: gene loci rs671, rs1329149, age and alcohol consumption) through the crossover analysis, which was not evident on logistic regression.


CONCLUSIONS
In conclusion, the method based on crossover analysis-logistic regression is successful in assessing additive and multiplicative gene-environment interactions, and in revealing synergistic effects of gene loci rs671 and rs1329149 with alcohol consumption in the pathogenesis and development of colorectal cancer.
Department of Health Statistics, Third Military Medical University, Chongqing, China.
Ya-Zhou
YZ
Wu
Huan
H
Yang
Ling
L
Zhang
Yan-Qi
YQ
Zhang
Ling
L
Liu
Dong
D
Yi
Jia
J
Cao
D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000209:etiology*; D018592:Cross-Over Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction / Q000706:statistics & numerical data*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors