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The HER2 I655V Polymorphism and Risk of Breast Cancer in Women < Age 40 Years¹

Cancer Genetics Laboratory, Victorian Breast Cancer Research Consortium, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria 3002 [K. G. M., S. W. B., I. G. C.]; Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Victoria [D. M. G., R. L. M., G. S. D., J. L. H.] and Cancer Epidemiology Centre, The Cancer Council Victoria [G. G. G.], Carlton, Victoria; Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand and (previously) Cancer Epidemiology Research Unit, The Cancer Council of New South Wales, Sydney, New South Wales [M. R. E. M.]; and Department of Pathology, The University of Melbourne, Parkville, Victoria 3053 [M. C. S.], Australia

The HER2 gene controls cellular function and has prognostic significance in breast cancer. The I655V polymorphism was associated with increased risk of breast cancer in Chinese women under the age of 45 years and in women with a first-degree family history of the disease. These associations, however, have not been confirmed in several studies of older women. We conducted a population-based case-control-family study of the I655V polymorphism using 409 Australian women with breast cancer diagnosed before the age of 40 years and 299 controls frequency matched for age. The I655V polymorphism was more common in cases (P = 0.01). A recessive model, in which homozygotes were associated with an adjusted odds ratio of 2.8 (95% confidence interval 1.3–6.2; P = 0.005), gave the best fit under parsimony. Although the biological role of the I655V polymorphism is not known, large independent studies of early onset breast cancer are warranted to attempt to replicate this finding.

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