Oligogenic combinations associated with breast cancer risk in women under 53 years of age

Common, but weakly penetrant, functional polymorphisms probably account for most of the genetic risk for breast cancer in the general population. Current polygenic risk models assume that component genes act independently. To test for potential gene-gene interactions, single nucleotide polymorphisms...

Full description

Saved in:
Bibliographic Details
Published in:Human genetics 2005-02, Vol.116 (3), p.208-221
Main Authors: ASTON, Christopher E, RALPH, David A, MITCHELL, Debra S, SHIMASAKI, Craig D, MULVIHILL, John J, JUPE, Eldon R, LALO, Dominique P, MANJESHWAR, Sharmila, GRAMLING, Bobby A, DEFREESE, Daniele C, WEST, Amy D, BRANAM, Dannielle E, THOMPSON, Linda F, CRAFT, Melissa A
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Biological and medical sciences
Breast cancer
Breast Neoplasms - genetics
Cancer
Case-Control Studies
Cell cycle
Classical genetics, quantitative genetics, hybrids
Epistasis, Genetic
Female
Fundamental and applied biological sciences. Psychology
Gene Frequency
Genes
Genetic aspects
Genetic Predisposition to Disease
Genetics of eukaryotes. Biological and molecular evolution
Health sciences
Human
Humans
Lubrication and lubricants
Medical research
Metabolism
Middle Aged
Mutation
Odds Ratio
Oncology, Experimental
Physiology
Polymorphism, Single Nucleotide
Risk
Risk assessment
Risk factors
Single nucleotide polymorphisms
Womens health
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Common, but weakly penetrant, functional polymorphisms probably account for most of the genetic risk for breast cancer in the general population. Current polygenic risk models assume that component genes act independently. To test for potential gene-gene interactions, single nucleotide polymorphisms in ten genes with known or predicted roles in breast carcinogenesis were examined in a case-control study of 631 Caucasian women diagnosed with breast cancer under the age of 53 years and 1,504 controls under the age of 53 years. Association of breast cancer risk with individual genes and with two- and three-gene combinations was analyzed. Sixty-nine oligogenotypes from 37 distinct two- and three-gene combinations met stringent criteria for significance. Significant odds ratios (ORs) covered a 12-fold range: 0.5-5.9. Of the observed ORs, 17% differed significantly from the ORs predicted by a model of independent gene action, suggesting epistasis, i.e., that these genes interact to affect breast cancer risk in a manner not predictable from single gene effects. Exploration of the biological basis for these oligogenic interactions might reveal etiologic or therapeutic insights into breast cancer and other cancers.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-004-1206-7