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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

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

IOS Press GSTT1 gene deletion is associated with lung cancer in Mexican patients

Abstract. Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer

Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13)(q26.2;p11.2): Further Delineation of 3q Duplication Syndrome

Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype

Ultraviolet-A Light Induces Micronucleated Erythrocytes in Newborn Rats

Background: Ultraviolet-A (UV-A) light induce DNA damage by creating pyrimidine dimers, or indirectly affects DNA by the formation of reactive oxygen species. The objective was to determine DNA damage by micronucleus test in neonatal rats exposed to UV-A light. Methods: Rat neonates were exposed to light from a LED lamp (control group), to UV-C light 254 nm (control group to desquamation skin) or UV-A light 365 nm and in one group the dams were supplemented with folic acid (FA), to determine micro nucleated erythrocytes (MNE) and micro nucleated polychromatic erythrocytes (MNPCE) in peripheral blood of offspring. Results: All the rat neonates exposed to UV-C lamp showed desquamation skin, while for UV-A lamp no desquamation was observed, and there was MNE differences in all sampling times (P<0.02) and for MNPCE in 9 min group (P=0.001). No differences between the groups with and without FA were observed. Conclusion: Increased MNE frequencies without apparent damage to the skin could be induced with UV-A light exposure. Under these conditions, FA no protected against UV-A light exposure. This study shows a manner to quantify the genotoxic effects of UV-A light in peripheral blood erythrocytes of rat neonates

Apolipoprotein E genotypes in Mexican patients with Parkinson&apos;s disease

Abstract. Background: The association of the apolipoprotein (Apo E) -epsilon4 allele to neurodegenerative diseases such as Parkinson&apos;s disease (PD) has been analyzed in several studies. This association has been identified by amyloid deposits and neurofibrillary tangles in the brains of patients with neurodegenerative diseases. Method: In this study the possible relationship between Apo E alleles and PD patients was analyzed in 105 patients with PD and 107 healthy controls from a Mexican population. Results: Allele analysis in PD vs. controls was: ε2 in 6% and 2.3%, respectively; ε3 in 73% and 88.3%; and ε4 in 21% and 9.4%. The ε3 allele showed a protective risk effect with an Odds ratio (OR) of 0.36 (95%CI 0.20-0.61) and p &lt; 0.05; contrary results were observed for the ε4 allele, which showed an increased risk for PD, with an OR of 2.57(95% CI 1.42-4.79) and p &lt; 0.05. Upon multivariate analysis showed PD risk was evident in patients who were carriers of the genotype ε3/ε4; age group (fifty or more years) and had exposure to pesticides and solvents (p &lt; 0.05). Conclusions: The ε3/ε3; ε3/ε4 genotypes of the Apo E, were positively associated with sporadic PD

Micronucleated erythrocytes in newborns rats exposed to three different types of ultraviolet-A (UVA) lamps from commonly uses devices

Exposure to ultraviolet-A (UVA) light can accidentally cause adverse effects in the skin and eyes. UVA induces DNA damage directly by creating pyrimidine dimers or by the formation of reactive oxygen species that can indirectly affect DNA integrity. UVA radiation is emitted by lamps from everyday devices. In adult rats, micronucleated erythrocytes (MNE) are removed from the circulation by the spleen. However, in newborn rats, MNE have been observed in peripheral blood erythrocytes. The objective of this study was to use micronucleus tests to evaluate the DNA damage caused in newborn rats exposed to UVA light from three different types of UVA lamps obtained from commonly used devices: counterfeit detectors, insecticide devices, and equipment used to harden resins for artificial nails. Rat neonates were exposed to UVA lamps for 20 min daily for 6 days. The neonates were sampled every third day, and the numbers of MNE and micronucleated polychromatic erythrocytes (MNPCE) in the peripheral blood were determined. The rat neonates exposed to the three types of UVA lamps showed increased numbers of MNE and MNPCE from 48 h to 144 h (P < 0.05 and P < 0.001 respectively). However, no relationship was observed between the number of MNE and the wattage of the lamps. In conclusion, under these conditions, UVA light exposure induced an increase in MNE without causing any apparent damage to the skin