Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women

Abstract

ABSTRACT. The tumor necrosis factor-alpha (TNF-α) gene plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, coagulation, insulin resistance, and endothelial function. Polymorphisms of TNF-α have been associated with cancer. We examined the role of the -308G>A polymorphism in this gene by comparing the genotypes of 294 healthy Mexican women with those of 465 Mexican women with breast cancer. The observed genotype frequencies for controls and breast cancer patients were 1 and 14% for AA, 13 and 21% for GA, and 86 and 65% for GG, respectively. We found that the odds ratio (OR) for AA genotype was 2.4, with a 95% confidence interval (95%CI) of 5.9-101.1 (P = 0.0001). The association was also evident when comparing the distribution of the AA-GA genotype in patients in the following categories: 1) premenopause and obesity I (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR = 2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR = 1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2 neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2-6.6, P = 0.016), and 6) nodule metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038). We concluded that the genotypes AA-GA of the -308G>A polymorphism in TNF-α significantly contribute to breast cancer susceptibility in the analyzed sample from the Mexican population.

Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients

“…The rs361525 minor allele is only present in the heterozygous genotype, and has previously been reported to be present at a frequency of 0.1-0.2%, based on different population data (Mohamed et al, 2010;Vázquez-Huerta et al, 2014). Although these polymorphisms have been connected to various diseases, including CRC (Fan et al, 2011;Shen et al, 2011;Cereda et al, 2012;Chu et al, 2012;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014;Vázquez-Huerta et al, 2014), study results have been inconsistent. The aim of this investigation was to measure TNF-α concentration in the plasma of Mexican CRC patients and determine its relationship with the -308G>A and -238G>A polymorphisms and haplotypes of the TNF-α gene.…”

“…The -308 (rs1800629) and -238 (rs361525) polymorphisms in the promoter region of the TNF-α gene have been reported to correlate with increased TNF-α production (Cereda et al, 2012). Studies have also associated these polymorphisms with complex diseases, including breast cancer and CRC (Fan et al, 2011;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014). According to National Center for Biotechnology Information 2012 population data, the rs1800629 minor allele (A) frequency is 5-10, 0.8-14, 0-2, and 0-8% among European, African, Asian, and Mexican populations, respectively (Parra-Rojas et al, 2006;Gómez Flores-Ramos et al, 2013).…”

“…TNF-α also plays a role in angiogenesis (Cereda et al, 2012;Gómez Flores-Ramos et al, 2013) by inducing the expression of adhesion molecules and facilitating the invasion of metastatic tumor cells (Gómez FloresRamos et al, 2013;Zelová and Hošek, 2013). In vitro and in vivo studies have shown that high levels of TNF-α are associated with poor prognoses in cancer patients due to its tumorigenic effects (Champ et al, 2012;Gómez Flores-Ramos et al, 2013). Several studies have demonstrated a significant association between cytokine levels and increased CRC risk (Fan et al, 2011) or severity (Stanilov et al, 2014).…”

“…The soluble TNF-α molecule binds to its receptors, TNFR1 and TNFR2, to stimulate the expression of the JUN oncogene, which participates in apoptosis. TNF-α also plays a role in angiogenesis (Cereda et al, 2012;Gómez Flores-Ramos et al, 2013) by inducing the expression of adhesion molecules and facilitating the invasion of metastatic tumor cells (Gómez FloresRamos et al, 2013;Zelová and Hošek, 2013). In vitro and in vivo studies have shown that high levels of TNF-α are associated with poor prognoses in cancer patients due to its tumorigenic effects (Champ et al, 2012;Gómez Flores-Ramos et al, 2013).…”

“…Studies have also associated these polymorphisms with complex diseases, including breast cancer and CRC (Fan et al, 2011;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014). According to National Center for Biotechnology Information 2012 population data, the rs1800629 minor allele (A) frequency is 5-10, 0.8-14, 0-2, and 0-8% among European, African, Asian, and Mexican populations, respectively (Parra-Rojas et al, 2006;Gómez Flores-Ramos et al, 2013). The rs361525 minor allele is only present in the heterozygous genotype, and has previously been reported to be present at a frequency of 0.1-0.2%, based on different population data (Mohamed et al, 2010;Vázquez-Huerta et al, 2014).…”