墨西哥女性中RETN和CAP1基因单核苷酸多态性、表达及血清抵抗素水平与乳腺癌的关联
Association of RETN and CAP1 SNPs, Expression and Serum Resistin Levels with Breast Cancer in Mexican Women.
作者信息
Muñoz-Palomeque Alejandrina, Guerrero-Ramirez Miguel Angel, Rubio-Chavez Lidia Ariadna, Rosales-Gomez Roberto Carlos, Lopez-Cardona Maria Guadalupe, Barajas-Avila Victor Hugo, Delgadillo-Barrera Alfredo, Canton-Romero Juan Carlos, Montoya-Fuentes Hector, Garcia-Cobian Teresa Arcelia, Gutierrez-Rubio Susan Andrea
机构信息
1 Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud , Universidad de Guadalajara, Guadalajara, Jalisco, Mexico .
2 Unidad de Medicina Genomica y Genetica, Hospital Dr. Valentin Gomez Farias, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado , Zapopan (ISSSTE), Jalisco, Mexico .
出版信息
Genet Test Mol Biomarkers. 2018 Apr;22(4):209-217. doi: 10.1089/gtmb.2017.0212. Epub 2018 Mar 20.
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.
背景
乳腺癌是全球女性中最常见的癌症。约70%的女性乳腺癌患者体重指数（BMI）>25。在肥胖状态下，脂肪组织会分泌额外的抵抗素，其通过作用于腺苷酸环化酶相关蛋白1（CAP1）产生促炎效应。多项研究已将RETN基因单核苷酸多态性（SNP）rs1862513（-420C<G）与血清抵抗素水平及乳腺癌相关联。位于细胞外结构域的CAP1基因SNP rs35749351（错义突变，Arg294His）此前尚未在癌症研究中涉及。本研究比较了患者与对照之间这两个SNP、各同源基因两个等位基因的mRNA表达水平以及血清抵抗素水平，以确定它们与墨西哥女性乳腺癌的关联。
材料与方法
本研究纳入308名对照和100名女性乳腺癌患者。通过PCR-RFLP从外周血分离的DNA中检测SNP。在肿瘤组织中使用水解探针进行基因表达检测。通过ELISA从血清样本中定量抵抗素水平。
结果
与CC和GG基因型相比，RETN rs1862513CG/GG和CAP1 rs35749351GA/AA基因型分别使乳腺癌风险增加1.61倍和2.193倍。同样，rs1862513的G等位基因携带者和rs35749351的A等位基因携带者与C和G等位基因携带者相比，乳腺癌风险分别增加1.51倍和2.217倍。rs1862513GG/rs35749351AA基因型组合使乳腺癌风险增加两倍。绝经后乳腺癌女性的血清抵抗素水平高于绝经后对照。组织CAP1表达在分子亚型和转移方面存在差异。
结论
RETN和CAP1多态性及基因表达可能是乳腺癌风险的潜在生物标志物。
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