Statistical methods for detecting genetic interactions: a head and neck squamous-cell cancer study.
Tobacco smoke and occupational exposures to chemicals such as polycyclic aromatic hydrocarbons (PAHs) are, aside from alcohol, the major risk factors for development of head and neck squamous-cell cancer (HNSCC). In this study, new statistical methods were applied. We employ new statistical methods to detect genetic interactions perhaps of higher order, that might play a role in developing HNSCC. The underlying study comprises 312 HNSCC cases and 300 controls. Single-nucleotide polymorphisms (SNPs) of PAH metabolizing and repair enzymes, somatic p53 mutations, and tobacco smoke were examined. Key statistical tools for our analysis are methods of unsupervised and supervised learning. In unsupervised learning, one performs cluster analyses based on well-known and new distance measures to find differences in the SNP patterns of cases and controls, and to understand the role of p53. Our main goal in supervised learning was to identify SNPs and SNP interactions that are likely to alter the susceptibility to HNSCC. Logic regression, a classification method well suited for SNPs, was employed as well as a Bayesian generalization that allows for incorporating additional expert knowledge. These methods detected several important interactions, such as an association between CYP1B1, tobacco smokes and p53 mutations and some interactions between CYP1B1 and glutathione S-transferases in smokers, which included a three-way interaction between CYP1B1, CYP2E1-70G>T, and GSTP1 (exon 5).
Fakultät Statistik, Collaborative Research Centre 475, Technische Universität Dortmund, Dortmund. ickstadt@statistik.uni-dortmund.de
Katja
K
Ickstadt
Martin
M
Schäfer
Arno
A
Fritsch
Holger
H
Schwender
Josef
J
Abel
Hermann M
HM
Bolt
Thomas
T
Brüning
Yon-Dschun
YD
Ko
Hans
H
Vetter
Volker
V
Harth
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001499:Bayes Theorem; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D065633:Cytochrome P-450 CYP1B1; D004273:DNA, Neoplasm / Q000097:blood; D003627:Data Interpretation, Statistical; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D014029:Tobacco Use Disorder / Q000235:genetics
D004273:DNA, Neoplasm; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D005982:Glutathione Transferase