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.