Associations between Breast Cancer Susceptibility Gene Polymorphisms and Clinicopathological Features

• Published in: Clinical cancer research 2004-01, Vol.10 (1), p.124-130
• Main Authors: HAN, Wonshik, KANG, Daehee, AE PARK, In, WON KIM, Seok, YEON BAE, Ji, CHUNG, Ki-Wook, NOH, Dong-Young
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; Antineoplastic agents; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Biomarkers, Tumor - genetics; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1B1; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Korea - epidemiology; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide - genetics; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Risk Factors; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-0834-3

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.