Variability in loss of constitutional heterozygosity across loci and among individuals: association with candidate genes in ductal breast carcinoma

Molecular Carcinogenesis
T R RebbeckK H Buetow

Abstract

Genes involved in the metabolic activation or detoxification of environmental carcinogens may contribute to breast cancer susceptibility by influencing rates of somatic mutation. To examine this hypothesis, we studied the association between loss of constitutional heterozygosity (LOH) in ductal breast tumors and allelic variability in genes that regulate the metabolism of environmental carcinogens. LOH was measured by typing the tumor and normal tissue of 28 breast cancer cases at 33 chromosomal loci by using highly polymorphic tetranucleotide repeat markers. Genotypes in non-tumor tissue were also measured at the cytochrome P450 1A1 (CYP1A1), cytochrome P450 2D6 (CYP2D6), glutathione-s-transferase mu (GSTM), epoxide hydrolase (EH), and NAD(P)H:quinone oxidoreductase (NQO1) loci. The observed proportion of LOH was 11% overall and ranged from 0% to 37% across loci. LOH greater than 20% was observed on chromosomes 1p, 2p, 10q, 11q, 17p, and 18q. The observed proportion of LOH ranged from 0% to 67% among individuals. An elevated proportion of LOH was observed for genotypes at CYP2D6 (17% for the 1/1 and 1/2 genotypes vs 8% for the 2/ 2 genotype), NQO1 (13% for the 1/2 and 2/2 genotypes vs 8% for the 1/1 genotype), and GSTM (15% fo...Continue Reading

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Citations

Dec 20, 2003·Pharmacogenomics·Stella C LymberisSilvia C Formenti
Nov 24, 2004·Drug Metabolism Reviews·David Ross
Feb 19, 2011·Genetic Testing and Molecular Biomarkers·Virendra SinghMahendra Pratap Singh
Mar 3, 2011·Journal of Neurosurgery. Pediatrics·Pawel G OchalskiIan F Pollack

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