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  • Title: Allelic imbalance of HER-2 codon 655 polymorphism among different religious/ethnic populations of northern Greece and its association with the development and the malignant phenotype of breast cancer.
    Author: Papadopoulou E, Simopoulos K, Tripsianis G, Tentes I, Anagnostopoulos K, Sivridis E, Galazios G, Kortsaris A.
    Journal: Neoplasma; 2007; 54(5):365-73. PubMed ID: 17918664.
    Abstract:
    Alterations of c-erbB-2 (neu or HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancer. A single nucleotide polymorphism (SNP) at codon 655 resulting in a G to A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer. This study aims to determine the prevalence of the HER-2 genotype and its association with breast cancer in the Greek Christian and Greek Muslim population of Thrace, Greece. In this case-control study, we genotyped 56 patients (43 Christians and 13 Muslims) with primary breast cancer and 45 healthy women (32 Christians and 13 Muslims) for the Ile655Val polymorphism, with the PCR-RFLP method. The Val allele and the Val-containing genotypes were significantly more frequent in Muslims than in Christians (p=0.020 and p=0.008, respectively). Among the Greek Christian population, a 5-fold and a 3.1-fold increase in risk of breast cancer was associated with the Val-Val genotype and the Ile-Val or Val-Val genotypes (95% CI, 1.3-18.4; p=0.017 and aOR, 3.1; 95% CI, 1.2-8.3; p=0.025; respectively) compared to homozygous Ile-Ile. No significant association was found in the Muslim population. Among the entire cohort, the Val allele confers a modest increase in breast cancer risk (OR, 2.6; 95% CI, 0.9-7.6; p=0.076, for Val-Val and OR, 2.2; 95% CI, 0.9-5.2; p=0.079 for Ile-Val or Val-Val). This effect was even more pronounced in younger women. Among breast cancer patients, invasive carcinomas, low differentiation tumors, advanced stages, positive lymph nodes, high number of lymph nodes and HER-2 overexpression were more frequent in patients with allele Val than those with allele Ile. Our study proposes the allelic imbalance of Ile655Val polymorphism between Greek Christian and Greek Muslim populations of Thrace contributes to the inconsistent association between this SNP and breast cancer risk across these two different ethnic groups. The association of the HER-2 genotype with clinicopathologic characteristics and HER-2 expression may indicate its possible implication on the more aggressive phenotype.
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