CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations

• Published in: Breast cancer research : BCR Vol. 14; no. 4; p. R105
• Main Authors: Jiang, Lan, Deng, Jieqiong, Zhu, Xun, Zheng, Jian, You, Yonghe, Li, Na, Wu, Hongchun, Lu, Jiachun, Zhou, Yifeng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.07.2012; BioMed Central
• Subjects: 3' Untranslated Regions; Adult; Aged; Alleles; Asian Continental Ancestry Group - genetics; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Case-Control Studies; China; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; MicroRNAs - genetics; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Prognosis
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/bcr3225

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 (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis. Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied. Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 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. These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.