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Association of RETN and CAP1 SNPs, Expression and Serum Resistin Levels with Breast Cancer in Mexican Women.

BACKGROUND
Breast cancer is the most common cancer in women worldwide. Approximately 70% of female breast cancer patients have a body mass index (BMI) >25. In obesity, adipose tissue secretes additional resistin, which prompts a proinflammatory effect through its action on adenylate cyclase-associated protein 1 (CAP1). Several studies have associated the RETN gene single nucleotide polymorphism (SNP) rs1862513 (-420C<G) with serum resistin levels and breast cancer. The CAP1 gene SNP rs35749351 (missense, Arg294His), located in the extracellular domain, has not previously been studied in cancer. These two SNPs, the mRNA expression levels of the two alleles for each of the cognate genes, and the serum resistin levels were compared between patients and controls to determine their association with breast cancer in Mexican women in this study.


MATERIALS AND METHODS
This study included 308 controls and 100 female patients with breast cancer. SNPs were detected by PCR-RFLP from DNA isolated from peripheral blood. Gene expression was performed with hydrolysis probes in tumor tissue. Resistin levels were quantified from serum samples by ELISA.


RESULTS
The RETN rs1862513CG/GG and CAP1 rs35749351GA/AA genotypes were associated with 1.61 and 2.193-fold increased risks of breast cancer, respectively, compared with the CC and GG genotypes. Similarly, carriers of the G allele of rs1862513 and the A allele of rs35749351, had 1.51 and 2.217-fold increased risks of breast cancer compared with the C and G alleles, respectively. The rs1862513GG/rs35749351AA genotype combination increased breast cancer risk by twofold. Serum resistin levels in postmenopausal breast cancer women were higher compared with postmenopausal controls. Tissue CAP1 expression showed differences with regard to molecular subtypes and metastases.


CONCLUSION
The RETN and CAP1 polymorphisms and gene expression may be potential biomarkers for breast cancer risk.