Discovering interactions among BRCA1 and other candidate genes associated with sporadic breast cancer.
Analysis of a subset of case-control sporadic breast cancer data, [from the National Cancer Institute's Cancer Genetic Markers of Susceptibility (CGEMS) initiative], focusing on 18 breast cancer-related genes with 304 SNPs, indicates that there are many interesting interactions that form two- and three-way networks in which BRCA1 plays a dominant and central role. The apparent interactions of BRCA1 with many other genes suggests the conjecture that BRCA1 serves as a protective gene and that some mutations in it or in related genes may prevent it from carrying out this protective function even if the patients are not carriers of known cancer-predisposing BRCA1 mutations. The method of analysis features the evaluation of the effect of a gene by averaging the effects of the SNPs covered by that gene. Marginal methods that test one gene at a time fail to show any effect. That may be related to the fact that each of these 18 genes adds very little to the risk of cancer. Analysis that relates the ratio of interactions to the maximum of the first-order effects discovers significant gene pairs and triplets.
Lo
Shaw-Hwa
SH
Department of Statistics, Columbia University, New York, NY 10027, USA. slo@stat.columbia.edu
Chernoff
Herman
H
Cong
Lei
L
Ding
Yuejing
Y
Zheng
Tian
T
D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D053263:Gene Regulatory Networks / Q000502:physiology*; D019398:Genes, BRCA1 / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D019313:BRCA1 Protein; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins