Abstract
BackgroundCD44 encoded by a single gene is a cell surface transmembrane glycoprotein. Exon 2 is one of the important exons to bind CD44 protein to hyaluronan. Experimental evidences show that hyaluronan–CD44 interaction intensifies the proliferation, migration, and invasion of breast cancer cells. Therefore, the current study aimed at investigating the association between specific polymorphisms in exon 2 and its flanking region of CD44 with predisposition to breast cancer.MethodsIn the current study, 175 Iranian female patients with breast cancer and 175 age-matched healthy controls were recruited in biobank, Breast Cancer Research Center, Tehran, Iran. Single nucleotide polymorphisms of CD44 exon 2 and its flanking were analyzed via polymerase chain reaction and gene sequencing techniques. Association between the observed variation with breast cancer risk and clinico-pathological characteristics were studied. Subsequently, bioinformatics analysis was conducted to predict potential exonic splicing enhancer (ESE) motifs changed as the result of a mutation.ResultsA unique polymorphism of the gene encoding CD44 was identified at position 14 nucleotide upstream of exon 2 (A37692→G) by the sequencing method. The A > G polymorphism exhibited a significant association with higher-grades of breast cancer, although no significant relation was found between this polymorphism and breast cancer risk. Finally, computational analysis revealed that the intronic mutation generated a new consensus-binding motif for the splicing factor, SC35, within intron 1.ConclusionsThe current study results indicated that A > G polymorphism was associated with breast cancer development; in addition, in silico analysis with ESE finder prediction software showed that the change created a new SC35 binding site.
Highlights
CD44 encoded by a single gene is a cell surface transmembrane glycoprotein
Distribution of polymorphisms in exon 2 and its flanking of CD44 Sequence analysis showed a unique polymorphism between CD44 exon 2 and its upstream intron
The risk of breast cancer related to CD44 polymorphism was further examined with stratification by age, family history of breast cancer, pathological type, clinical stage, estrogen/progesterone receptor status (ER, Progesterone receptor (PR)), and Her2 expression
Summary
CD44 encoded by a single gene is a cell surface transmembrane glycoprotein. Exon 2 is one of the important exons to bind CD44 protein to hyaluronan. History of the disease is one of the most important risk factors for breast cancer [2, 3]. The most important familial breast cancer susceptibility genes are BRCA1 and BRCA2, which are inherited with autosomal dominant pattern. The carriers of mutant genes have a significantly greater risk for developing breast and ovary cancers [4, 5]. According to the current estimates, known breast cancer susceptibility genes are responsible for only less than 25% of the familial clustering of breast cancer [6]. This fact requires the execution of further studies to detect other responsible genes
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