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-oncogene have been implicated in the carcinogenesis and prognosis of breast cancer. A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer. We evaluated this hypothesis in a subgroup of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China.


METHODS
Genomic DNA from 339 patients with breast cancer and 361 healthy control subjects was examined for the Val(655)Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All study subjects completed a structured questionnaire during an in-person interview. 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 subjects 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 elevated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.0-2.0; P =. 05) after adjustment for age, educational level, study period, history of breast fibroadenoma, leisure physical activity, and age at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% CI = 1.8-113.4). The association was more pronounced among younger women (</=45 years) 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 women and 1.0 (95% CI = 0.5-1.9) for older women.


CONCLUSIONS
Results of this study suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.
Xie
D
D
Department of Epidemiology and Biostatistics, University of South Carolina School of Public Health and South Carolina Cancer Center, Columbia, SC 29203, USA.
Shu
X O
XO
Deng
Z
Z
Wen
W Q
WQ
Creek
K E
KE
Dai
Q
Q
Gao
Y T
YT
Jin
F
F
Zheng
W
W
D000328:Adult; D000367:Age Factors; D019943:Amino Acid Substitution; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D015444:Exercise; D005260:Female; D018226:Fibroadenoma / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D018734:Genes, erbB-2; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007532:Isoleucine; D008572:Menarche; D008875:Middle Aged; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D014633:Valine
D007532:Isoleucine; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D014633:Valine; C000715470:MAS1 protein, human