Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk

Background: Alterations of the HER2 (also known as erbB-2 or neu) proto-onc ogene have been implicated in the carcinogenesis and prognosis of breast ca ncer. A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)I le]) in the transmembrane domain-coding region of this gene has been identi fied and may be associated with the risk of breast cancer. We evaluated thi s hypothesis in a subgroup of women who participated in a large-scale, popu lation-based, case-control study of breast cancer in Shanghai, China. Metho ds: Genomic DNA from 339 patients with breast cancer and 361 healthy contro l subjects was examined for the Val(655)Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All st udy subjects completed a structured questionnaire during an inperson interv iew. All P values are from two-sided tests. Results: We found that 25.1% of the case patients and 21.7% of the control subjects were heterozygous for the Val allele and 3.2% of the case patients and 0.3% of the control subjec ts were homozygous for this allele (P = .005). Compared with women with the Ile/Ile genotype, women who had the Ile/Val or Val/Val genotype had an ele vated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CT] = 1.0-2.0; P = .05) after adjustment for age, educational level, stud y period, history of breast fibroadenoma, leisure physical activity, and ag e at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% Ct = 1.8-113.4). The associa tion nas more pronounced among younger women (less than or equal to 45 year s) than among older women (>45 years). The adjusted OR associated with the Val allele was 1.7 (95% CI = 1.1-2.6) for younger nomen and 1.0 (95% CI = 0 .5-1.9) for older women. Conclusions: Results of this study suggest that po lymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.