Associations between breast cancer susceptibility gene polymorphisms and clinicopathological features.

PURPOSE Genetic polymorphisms may affect not only cancer development but also cancer progression, and as a result could influence cancer phenotypes. The aim of this study was to examine the relationship between breast cancer susceptibility gene polymorphisms and clinicopathological features. EXPERIMENTAL DESIGN We genotyped 664 Korean primary breast cancer patients for 17 single-nucleotide polymorphisms (SNPs) in nine genes, using a high-throughput SNP scoring method. RESULTS CYP1A1 codon 462 Ile/Val or Val/Val variants and the CYP1B1 codon 432 Leu/Val variant were found more in breast cancer patients </=35 years of age at onset than the common homozygote [odds ratio (OR), 1.6 and 1.7, respectively]. In combination analysis of these two SNPs, the OR was 1.9 when one of them was heterozygous or a rare homozygous form, and increased to 2.3 when both were variants (P = 0.006). Cases with Ile/Val at CYP1A1 codon 462 were 2.6-fold and those with Val/Val were 5.1-fold more likely to have first-degree relatives with breast cancer than those with Ile/Ile (P = 0.002). In the haplotype study of BRCA1, the 2430C/2731T/3667G/4427C/4956G homozygote showed less estrogen receptor negativity than the most common diplotype (OR, 0.5; 95% confidence interval, 0.26-0.94). TP53 codon 72 Arg/Pro or Pro/Pro variants were associated with negative axillary lymph node status (OR, 0.7; 95% confidence interval, 0.49-0.94). CONCLUSIONS These results indicate that polymorphisms of some selected breast cancer susceptibility genes are associated with the clinicopathological phenotypes of breast cancer.