Association of NFκß, TNFα, IL-6, IL-1ß, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population.

Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκß, IL-1ß, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. METHODS: We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. RESULTS: We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκß, -174 and -572 of IL-6, C/C of IL-1ß, -308 and -238 of TNFα, and T/T of LPL. In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. CONCLUSION: Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκß, IL-6, TNFα, IL-1ß, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.

Pathological characteristics, survival, and risk of breast cancer associated with estrogen and xenobiotic metabolism polymorphisms in Mexican women with breast cancer.

Prolonged exposure to estrogens is the main factor associated with the risk and prognosis of breast cancer (BC). The genes involved in the biotransformation of estrogens and xenobiotics have allelic variants with modified enzymatic activities. We investigated the association of nine polymorphisms of some genes from the classical estrogen pathway with the risk of breast cancer and their role in the clinicopathological characteristics of poor clinical prognosis in a sample of Mexican women with BC. METHODS: We included 150 controls and 150 cases matched by age. To analyze the selected polymorphisms, TaqMan assays and high-resolution melting (HRM) analysis were used. RESULTS: The polymorphisms of the genes ERα, CYP1A1, CYP1B1, COMT, MGMT, and XRCC1 were positively associated with the BC risk. We found negative associations between CYP1B1G/G genotype and tumor size, and status of lymph node, estrogen receptor, triple negative, and survival. CONCLUSIONS: The polymorphisms included in this study are associated not only with the risk of BC, but also with some clinicopathological characteristics for poor prognosis of patients with breast cancer, highlighting the important role of CYP1B1 Leu432Val polymorphism.

Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1(∗)2C, CYP1B1(∗)3 and COMT Val158Met allelic variants.

Exposure to estrogen and its metabolites, including catechol estrogens (CEs) and catechol estrogen quinones (CE-Qs) is closely related to breast cancer. Polymorphisms of the genes involved in the catechol estrogens metabolism pathway (CEMP) have been shown to affect the production of CEs and CE-Qs. In this study, we measured the induction of CYP1A1, CYP1B1, COMT, and GSTP1 by 17ß-estradiol (17ß-E2) in leukocytes with CYP1A1(∗)2C, CYP1B1(∗)3, COMT Val158Met and GSTP1 Ile105Val polymorphisms by semi quantitative RT-PCR and compared the values to those of leukocytes with wild type alleles; we also compared the differences in formation of 4- hydroxyestradiol (4-OHE2) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17ß-E2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE2 concentrations associated with allelic variants in response to exposure of 17ß-E2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.

Genetic susceptibility to lung cancer based on candidate genes in a sample from the Mexican Mestizo population: a case-control study.

BACKGROUND: Lung cancer (LC) is the leading cause of mortality caused by neoplasias worldwide. Although cigarette smoking is the primary cause, not all smokers develop LC. Polymorphic variations in genes associated with carcinogen metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk of developing LC. A polygenic cancer model was proposed, which considers genetic susceptibility to cancer is a global mechanism and suggests that it might be defined by the contributions of low-risk alleles in several candidate genes. This study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a case-control study of a sample of Mexican Mestizo population. METHODS: A case-control study was performed with a total of 572 unrelated individuals, including 190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic status of the individuals was determined by TaqMan probe and RFLP techniques. The association between LC and genotype score (GS) was assessed by logistic regression. RESULTS: The results suggests a protective effect of the genotypes Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1 rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03), and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that average cases have a larger number of risk alleles than controls (Student's t test -4.85, p = 0.001; OR 1.25, p < 0.001). CONCLUSIONS: Our results suggest significant differences between the GS for the cases and controls, which support the hypothesis underlying the additive and polygenic models for lung cancer risk depending on the polymorphisms in low-penetrance genes.

Polymorphisms of catechol estrogens metabolism pathway genes and breast cancer risk in Mexican women.

Breast cancer is associated to estrogen exposure. Allelic variants involved in estrogen metabolism might change the risk of developing this neoplasia. We examined the potential association of breast cancer risk in Mexican women with the polymorphisms CYP1A1 rs1048943, CYP1B1 rs1056836, COMT rs4680, GSTP1 rs1695, GSTT1 null and GSTM1 null which are involved in estrogen metabolism pathway. This study included 150 cases and 150 controls. A significant association was observed between, CYP1A1 rs1048943 (OR = 1.95, C.I. 1.13-3.36) and GSTP1 rs1695 (OR = 2.39, C.I. 1.24-4.24) polymorphisms with the risk of breast cancer. This risk was increased when the women were stratified according to their menopausal status. The results show that breast cancer risk significantly increases in women with 3-6 risk polymorphisms (OR = 3.75, C.I. 1.44-9.74).