CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations
Menée dans l'Est et le Sud de la Chine sur 1 853 patientes atteintes d'un cancer du sein et sur 1 992 témoins, cette étude montre qu'un polymorphisme à simple nucléotide du gène codant pour la protéine CD44 (rs13347 C>T) est associé au risque de cancer du sein et à la survie des patientes
INTRODUCTION:It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration, and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage case control study, we determined whether common functional tagSNPs are associated with breast cancer risk and prognosis.METHODS:Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1853 breast cancer patients and 1992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied.RESULTS:Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (OR=1.37, 95%CI=1.17-1.59 for ER positive patients; OR=2.37, 95%CI=2.00-2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower 5-year survival rate (HR=1.85, 95%CI=1.09-3.15, P=0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P<0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P<0.001) and western blotting (P=0.001) results.CONCLUSION:These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.
Breast Cancer Research , résumé, 2011