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Abstract. BACKGROUND: Polymorphism of the genes of Human Epidermal growth factor receptor1 (HER1) and receptor2 (HER2) have been reported to be linked to pathogenesis of several malignant tumors but still there is contradiction regarding their association with breast cancer. OBJECTIVE: In this case control study we aimed to analyze the frequency of HER1 R497K (rs 11543848) and HER2 I655V (rs 1136201) Polymorphisms in breast cancer. SUBJECT AND METHOD: The frequency of HER1 Arg(R) 497Lys (K) and HER2 Ile (I) 655Val (V) polymorphisms were tested in 64 breast cancer patients and 86 normal control by polymerase chain reaction followed by restriction fragment polymorphism detection. Immunohistochemical analysis was done for HER2 protein on the available 18 malignant tissue samples. RESULTS: HER1 497K and HER2 655V variant had significantly increased breast cancer risk (OR = 2.6, 95% CI 1.6-4.2, OR = 2.2, 95% CI 1.2-4.1, p < 0.05) respectively. Moreover, combined HER1K497 and HER2 V655 variant was detected in 26.6% malignant in comparison to 8.14% of control group (OR = 4.1, 95% CI 1.58-10.57), but, no significant association was noticed between both Polymorphisms and clinicopathological features of the disease. As regard HER2 immunohistochemical expression no significant correlation was revealed with HER2 655V polymorphism. CONCLUSIONS: Our findings suggest that HER1 497K and HER2 655V polymorphisms are potential risk factor for development of breast cancer.

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