Consumption of water contaminated by nitrate and its deleterious effects on the human thyroid gland: a review and update.

Nowadays, the nitrates have been established as carcinogenic components due to the endogenous formation of N-nitroso compounds, however, the consumption of water contaminated with nitrates has only been strongly related to the presence of methemoglobinemia in infants, as an acute effect, leaving out other side effects that demand attention. The thyroid gland takes relevance because it can be altered by many pollutants known as endocrine disruptors, which are agents capable of interfering with the synthesis of hormones, thus far, it is known that nitrates may disrupt the amount of iodine uptake causing most of the time hypothyroidism and affecting the metabolic functions of the organism in all development stages, resulting in an important health burden for the exposed population. Here, this review and update highlighted the impact of consumption of water contaminated with nitrates and effects on the thyroid gland in humans, concluding that nitrates could act as true endocrine disruptor.

FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women.

Nitrates in drinking water has been associated to adverse health effects, including changes in glucose and lipid levels, thyroid hormone imbalance and adverse reproductive effects. We analyzed metabolic and thyroid hormone alterations and genotoxic damage in women with chronic exposure to nitrates in drinking water. The concentration of nitrates in drinking water was quantified and according to this parameter, participants were divided into three exposure scenarios. Blood and urine samples were collected from 420 women living in Durango, Mexico and biomarkers were determined. We found nitrates concentrations in drinking water above the permissible limit (>50 mg/L), and an increase in the percentage of methemoglobin (p=0.0001), nitrite in blood plasma and urine (p=0.0001), glucose (p=0.0001), total cholesterol (p=0.001), LDL (p=0.001) and triglycerides (p=0.0001). We also found alterations in TSH (p=0.01), fT3 (p=0.0003), T4T (p=0.01) and fT4 (p=0.0004) hormones. Frequency of subclinical hypothyroidism was 8.33%; differences in FOXE1 (rs965513, rs1867277) genotypes distribution were found and both polymorphisms were associated with a decrease in TSH. A high percentage of micronucleus in binucleate lymphocyte cells was found (35%, p=0.0001). In conclusion, the chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women.

Regulation of the Tpo, Tg, Duox2, Pds, and Mct8 genes involved in the synthesis of thyroid hormones after subchronic exposure to sodium nitrate in female Wistar rats.

Nitrates are natural compounds present in soil and water; however, the intense use of fertilizers has increased their presence in groundwater with deleterious effects on human health. There is evidence of nitrates acting as endocrine disruptors; however, the underlying molecular mechanisms have not been fully described. Here, we investigated the effect of subchronic exposure to different concentrations of sodium nitrate in female Wistar rats, evaluating thyroid hormonal parameters, such as Nis transporter (Na+ /I- symporter, Slc5a5) and Tsh-R receptor protein expression, as well as transcription of the Tpo (thyroperoxidase), Tg (tiroglobulin), Duox2 (dual oxidase 2), Pds (pendrin), and Mct8 (Mct8 transporter, Slc16a2) genes. Hematological and histochemical changes in the liver and thyroid were also explored. Significant differences were found in platelet and leukocyte counts; although a significant increase in the weight of the thyroid gland was observed, no differences were found in the levels of the hormones Tsh, T3, and T4, but a modulation of the mRNA expression of the Tg, Tpo, Duox2, Mct8, and Pds genes was observed. Morphological changes were also found in liver and thyroid tissue according to the exposure doses. In conclusion, subchronic exposure to sodium nitrate induces leukocytosis consistent with an inflammatory response and upregulation of Sod2 in the liver and increases the expression of genes involved in the synthesis of thyroid hormones, keeping thyroid hormone levels stable. Histological changes in the thyroid gland suggest a goitrogenic effect.

Glutathione S-transferase activity and genetic polymorphisms associated with exposure to organochloride pesticides in Todos Santos, BCS, Mexico: a preliminary study.

The objective of this study was to identify and evaluate the impact of exposure to mixtures of organochloride pesticides (OCPs) in agricultural workers by detecting their effects on the activity of the enzyme glutathione S-transferase (GST) and the presence of polymorphisms of the GSTT1 and GSTM1 genes. The presence of OCPs was identified and quantified by gas chromatography, while spectrophotometry was used to measure enzymatic GST activity. The frequencies of the GSTM1 genotypes were analyzed by multiplex PCR. A total of 18 metabolites of OCPs were identified in the workers' blood, most of which are either prohibited (DDT and its metabolites p, p'DDD and p, p'DDE, dieldrin, endrin, aldrin) and/or restricted (δ hexachlorocyclohexane, cis chlordane, methoxychlor, and endosulfan). The results obtained indicate lower levels of GST activity at higher OCPs concentrations detected in blood from exposed workers, together with an increase in OCP levels in individuals who presented the GSTT1*0 and GSTM1*0 genotypes. These conditions place the detoxification process in agricultural workers with null polymorphisms in the GST genes and high concentrations of OCPs in the blood (especially DDT and its metabolites, DDD and DDE) at risk, and increase their susceptibility to develop serious diseases.

Differential Methylation in Promoter Regions of the Genes NR3C1 and HSP90AA1, Involved in the Regulation, and Bioavailability of Cortisol in Leukocytes of Women With Preeclampsia.

Introduction: Hypertensive disorders are of interest in obstetrics and gynecology because they are the second place among causes of maternal mortality and a source of complications in the short, mid, and long term. Even if the pathophysiological process behind preeclampsia (PE) is still unknown, stress factors have been revealed to play an important role in the genesis of this pathologic process. Methods: A case-control study was designed with the purpose of determining if there is a differential methylation in NR3C1, HSD11B2, CYP11A1, CRHBP, TEAD3, and HSP90AA1 genes, related to signaling of the hypothalamic-pituitary-adrenal axis, and its regulation on early-onset PE (EOPE). Results: A total of 20 cases and 20 controls were studied by DNA methylation analysis, demonstrating differences among groups in the percentage of methylation of the NR3C1 gene. After a contingency analysis, an odds ratio (OR) for PE of 12.25 was identified for NR3C1 and 9.9 for HSP90AA1 genes. NR3C1, TEAD3, and HSP90AA1 genes showed a positive correlation with the systolic and diastolic blood pressure levels with a p ≤ 0.05. Conclusion: This study found a differential methylation in the glucocorticoid receptor (GR) NR3C1 and its co-chaperone HSP90AA1 in women with PE, with a possible regulatory role in the response to stress in pregnancy and is a likely physiopathological mechanism in PE.

Identification of Multiple High-Risk Human Papillomavirus Infections in a Rural Population of Canatlan, Durango, Mexico.

Background: The human papillomavirus (HPV) is the most frequent etiological agent driving development of cervical cancer (CC); therefore typing and classifying the status of these infections are of great importance for treatment. The frequency of the various HPV types may change in relation to low-grade lesions and have the potential to cause more severe lesions. Objective: The purpose of this study was the identification and typing of HPV in a rural population in Mexico. Methods: Detection and typing were determined by PCR-RFLPs and confirmed by viral DNA sequencing. Results: HPV was detected in 17.28% of the samples, this was 3.58% higher than had been determined in a rural population in Central Mexico. Viral types 16, 18 and 52 were found most frequently. Analysis of all HPV-positive samples revealed that 14.3% had a single infection; 57.1% had a double infection; and 28.6% had a triple infection. Thus, 85.7% of positive cases presented with multiple infections with HPV16 being the most prevalent. Only the lifetime number of sexual partners was found to have an association with the colposcopic diagnoses (OR = 7.08; 95% CI: 1.68-29.8; p > 0.008). Conclusion: A higher frequency of multiple HPV infections was found among our test population compared to other rural populations in Durango and Central Mexico. HPV type 16 was the most frequent infection.

Self-assembled high molecular weight inulin nanoparticles: Enzymatic synthesis, physicochemical and biological properties.

Inulin has interesting physicochemical and functional properties, and therefore a wide range of applications in the food and medical industries. It has gained great traction due to its ability to form nanoparticles and its possible application as nanovehicle for drug delivery. In this work, we demonstrated that the enzymatically-synthesized high molecular weight (HMW) inulin forms stable spherical nanoparticles with an average diameter of 112 ± 5 nm. The self-assemblage of HMW inulin nanoparticles is carried out during enzymatic synthesis of the polymer, and become detectable after a certain critical aggregation concentration (CAC) is reached. Both, the CAC and nanoparticle size are influenced by the reaction temperature. These nanoparticles are not toxic for peripheral blood mononuclear cells, at concentrations below 200 µg/mL; no significant prebiotic potential was detected in cultures of 13 probiotic strains. This work contributes to a better understanding of the formation of HMW inulin nanoparticles and their biological properties.

Association of the Promoter Methylation and the rs12917 Polymorphism of MGMT with Formation of DNA Bulky Adducts and the Risk of Lung Cancer in Mexican Mestizo Population.

O6-Methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs the DNA damage caused by the tobacco habit, and low activity of this enzyme has been associated with a risk of lung cancer (LC). Our objective was to determine the association of the promoter methylation and the rs12917 polymorphism of MGMT with formation of DNA bulky adducts and the risk of LC in the Mexican Mestizo population. In this study are included 431 subjects. High-resolution melting analysis was used to determine the polymorphism MGMT rs12917 and methylation levels. DNA bulky adducts were determined by 32P-postlabeling. Our results showed that MGMT rs12917 and higher levels of methylation in the MGMT promoter are associated with the risk of LC. The levels of adducts are related with the phe/phe genotype and, only in the cases group, with the hypermethylation (>50%) of MGMT; however, this last association was not statistically significant.

Antibiotic resistance, virulence factors and genotyping of Pseudomonas aeruginosa in public hospitals of northeastern Mexico.

INTRODUCTION: Pseudomonas aeruginosa is the second most prevalent opportunistic pathogen causing nosocomial infections in Mexico. This study evaluated antibiotic resistance, production of virulence factors and clonal diversity of P. aeruginosa strains isolated from patients undergoing nosocomial infections in public hospitals of northeastern Mexico. METHODOLOGY: Ninety-two P. aeruginosa isolates from urine culture, Foley catheter, ear, wounds, respiratory tract secretions, scalp, blood culture, bronchoalveolar lavage, expectoration and cerebrospinal fluid causing nosocomial infections were analyzed. The isolates were identified by MALDI-TOF and antibiotic resistance profiles obtained by MicroScan®. The production of virulence factors was analyzed with spectrophotometric techniques and isolates genotyped by ERIC-PCR. RESULTS: Out of the 92 isolates, 26 (28.2%) were found to be multidrug resistant (MDR); 21 (22.7%) were classified as extremely drug resistant (XDR). Highest resistance rate was found for gatifloxacin (42%) while ciprofloxacin accounted for the antibiotic with the lowest resistance rate (2%). Bronchoalveolar lavage isolates produced the highest amounts of virulence factors: biofilm (44.4% ± 2.7%), elastase (58.5% ± 4.3%), alkaline protease (60.1% ± 5.0%); except for pyocyanin production. The ERIC-PCR assay showed 83 genetic patterns (90% clonal diversity) and 13 isolates had 100% genetic similarity, forming 4 real clones, 3 of these clones were obtained from different anatomical site and/or hospital. CONCLUSIONS: Antibiotic resistance and virulence factors production was heterogeneous among samples analyzed. Genotyping of P. aeruginosa strains showed high genetic diversity in the studied isolates.

Ontogenetic Change in the Venom of Mexican Black-Tailed Rattlesnakes (Crotalus molossus nigrescens).

Ontogenetic changes in venom composition have important ecological implications due the relevance of venom in prey acquisition and defense. Additionally, intraspecific venom variation has direct medical consequences for the treatment of snakebite. However, ontogenetic changes are not well documented in most species. The Mexican Black-tailed Rattlesnake (Crotalus molossus nigrescens) is large-bodied and broadly distributed in Mexico. To document venom variation and test for ontogenetic changes in venom composition, we obtained venom samples from twenty-seven C. m. nigrescens with different total body lengths (TBL) from eight states in Mexico. The primary components in the venom were detected by reverse-phase HPLC, western blot, and mass spectrometry. In addition, we evaluated the biochemical (proteolytic, coagulant and fibrinogenolytic activities) and biological (LD50 and hemorrhagic activity) activities of the venoms. Finally, we tested for recognition and neutralization of Mexican antivenoms against venoms of juvenile and adult snakes. We detected clear ontogenetic venom variation in C. m. nigrescens. Venoms from younger snakes contained more crotamine-like myotoxins and snake venom serine proteinases than venoms from older snakes; however, an increase of snake venom metalloproteinases was detected in venoms of larger snakes. Venoms from juvenile snakes were, in general, more toxic and procoagulant than venoms from adults; however, adult venoms were more proteolytic. Most of the venoms analyzed were hemorrhagic. Importantly, Mexican antivenoms had difficulties recognizing low molecular mass proteins (<12 kDa) of venoms from both juvenile and adult snakes. The antivenoms did not neutralize the crotamine effect caused by the venom of juveniles. Thus, we suggest that Mexican antivenoms would have difficulty neutralizing some human envenomations and, therefore, it may be necessary improve the immunization mixture in Mexican antivenoms to account for low molecular mass proteins, like myotoxins.

CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms are associated with heavy smoking, lung cancer, and chronic obstructive pulmonary disease in a mexican population.

BACKGROUND AND PURPOSE: Smoking is a major public health problem worldwide. Polymorphisms in CHRNA3, CHRNA5, and CHRNB4 receptors play a critical role in nicotine dependence, lung cancer (LC) risk, and chronic obstructive pulmonary disease (COPD). This study characterized the CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms in a Mexican population and its association with nicotine dependence, LC, and COPD. METHODS: The study included 312 healthy individuals, 74 LC cases and 117 COPD cases. Genotyping was performed using TaqMan probes, and the data were analyzed using logistic regression adjusted for covariates. RESULTS: The polymorphism CHRNA3 rs1051730 and CHRNA5 rs16969968 were in the Hardy-Weinberg equilibrium and the allelic frequency of the A allele was 0.15, for both polymorphisms. The smokers were stratified in heavy smokers and moderate/light smokers, and we found in A alleles an OR = 2.86 (P = 0.01) to CHRNA3 rs1051730 and OR = 3.12 (P = 0.03) to CHRNA5 rs16969968. In addition, the A alleles in CHRNA3 rs1051730 and CHRNA5 rs16969968 were associated with the risk for LC (OR = 1.66, P = 0.07 and OR = 1.57, P = 0.1, respectively) and for COPD (OR = 2.04, P = 0.01 and OR = 1.91, P = 0.02, respectively). CONCLUSION: CHRNA3/5 polymorphisms are associated with nicotine dependence, LC, and COPD in Mexicans.

Associations between sperm quality, DNA damage, and CYP1A1, GSTT1 and GSTM1 polymorphisms with 1-hydroxypyrene urinary levels in men occupationally exposed to polycyclic aromatic hydrocarbons.

PURPOSE: During recent decades, several reports have suggested a decrease in semen quality and DNA damage due in part to environmental toxicants and industrial chemicals. Among these xenobiotics, polycyclic aromatic hydrocarbons (PAHs) are of particular concern because of their remarkable mutagenic and carcinogenic properties and because several experimental and epidemiological studies have reported adverse effects of PAHs on male reproductive health and DNA structure. The aim of the study was to evaluate the association between 1-hydroxypyrene (1-OHP) urinary levels and sperm quality, DNA damage and the frequency of CYP1A1, GSTT1, and GSTM1 polymorphisms. METHODS: Semen, urine and blood samples were taken for sperm-quality assessment, 1-OHP urinary level measurement, DNA damage evaluation and polymorphism frequency analysis of three genes implicated in PAH metabolism in a total of 70 Mexican subjects exposed and nonexposed to PAHs. RESULTS: A significant decrease in sperm quality and increased DNA damage were registered in occupationally exposed volunteers. Polymorphisms modified the 1-OHP urinary levels; however, no associations were found between them. Inverse associations were registered between the sperm concentration/mL and 1-OHP levels and between tail lengths and the GSMT1 null genotype. CONCLUSIONS: Our data showed an inverse association between 1-OHP urinary levels and both sperm quality and the DNA integrity. Additionally, the heterozygote variants of CYP1A1-m1 and CYP1A1-m2 significantly increased the urinary excretion of 1-OHP, and the GSTM1 null variant was inversely associated with the comet parameters evaluated.

Biological and Proteolytic Variation in the Venom of Crotalus scutulatus scutulatus from Mexico.

Rattlesnake venoms may be classified according to the presence/absence and relative abundance of the neurotoxic phospholipases A 2 s (PLA 2 s), such as Mojave toxin, and snake venom metalloproteinases (SVMPs). In Mexico, studies to determine venom variation in Mojave Rattlesnakes (Crotalus scutulatus scutulatus) are limited and little is known about the biological and proteolytic activities in this species. Tissue (34) and venom (29) samples were obtained from C. s. scutulatus from different locations within their distribution in Mexico. Mojave toxin detection was carried out at the genomic (by PCR) and protein (by ELISA) levels for all tissue and venom samples. Biological activity was tested on representative venoms by measuring LD 50 and hemorrhagic activity. To determine the approximate amount of SVMPs, 15 venoms were separated by RP-HPLC and variation in protein profile and proteolytic activity was evaluated by SDS-PAGE (n = 28) and Hide Powder Azure proteolytic analysis (n = 27). Three types of venom were identified in Mexico which is comparable to the intraspecific venom diversity observed in the Sonoran Desert of Arizona, USA: Venom Type A (∼Type II), with Mojave toxin, highly toxic, lacking hemorrhagic activity, and with scarce proteolytic activity; Type B (∼Type I), without Mojave toxin, less toxic than Type A, highly hemorrhagic and proteolytic; and Type A + B, containing Mojave toxin, as toxic as venom Type A, variable in hemorrhagic activity and with intermediate proteolytic activity. We also detected a positive correlation between SVMP abundance and hemorrhagic and proteolytic activities. Although more sampling is necessary, our results suggest that venoms containing Mojave toxin and venom lacking this toxin are distributed in the northwest and southeast portions of the distribution in Mexico, respectively, while an intergradation in the middle of both zones is present.

LEP rs7799039, LEPR rs1137101, and ADIPOQ rs2241766 and 1501299 Polymorphisms Are Associated With Obesity and Chemotherapy Response in Mexican Women With Breast Cancer.

BACKGROUND: Obesity plays a major role in the pathogenesis of breast cancer. Leptin (LEP) and adiponectin (ADIPOQ) are important in the regulation of adipose tissue. The response to cancer treatment depends on the histological and molecular tumor type, clinical stage, and genetic variability that might promote carcinogenic development. The aim of this study was to investigate the association between overweight/obesity and polymorphisms in the LEP (rs7799039), LEP receptor (LEPR; rs1137101), and ADIPOQ genes (rs2241766, rs1501299) with the response to breast cancer treatment in Mexican women. PATIENTS AND METHODS: A sample of 177 patients with primary breast cancer (stage I-III) and who received neoadjuvant therapy were included. Polymorphisms were genotyped and their serum LEP concentrations (n = 59) were quantified. RESULTS: The patients' median age was 53.1 years, the frequency of overweight and obesity was 57 and 84 patients, respectively, 117 were postmenopausal, and 64 of the patients did not respond to chemotherapy. An association of the LEP rs7799039, LEPR rs1137101, and ADIPOQ rs1501299 polymorphisms with overweight/obesity was found. The patients who did not respond to treatment were more frequently obese, at clinical stage III, had metastases, and high levels of glucose. Moreover, in samples that were positive for estrogen receptor, higher levels of LEP were found, and in wild type genotypes for LEP rs7799039 and LEPR rs1137101. CONCLUSION: There was a direct association between the polymorphisms in LEP rs7799039 and ADIPOQ rs1501299 with overweight/obesity, and these genotypes affected the response to chemotherapeutic treatment, suggesting that an obesogenic microenvironment is more favorable for tumoral progression.

Characterization of different Capsicum varieties by evaluation of their capsaicinoids content by high performance liquid chromatography, determination of pungency and effect of high temperature.

The chili pepper is a very important plant used worldwide as a vegetable, as a spice, and as an external medicine. In this work, eight different varieties of Capsicum annuum L. have been characterized by their capsaicinoids content. The chili pepper fruits were cultivated in the Comarca Lagunera region in North of Mexico. The qualitative and quantitative determination of the major and minor capsaicinoids; alkaloids responsible for the pungency level, has been performed by a validated chromatographic procedure (HPLC-DAD) after a preliminary drying step and an opportune extraction procedure. Concentrations of total capsaicinoids varied from a not detectable value for Bell pepper to 31.84 mg g(-1) dried weight for Chiltepín. Samples were obtained from plants grown in experimental field and in greenhouse without temperature control, in order to evaluate temperature effect. Analysis of the two principal capsaicinoids in fruits showed that the amount of dihydrocapsaicin was always higher than capsaicin. In addition, our results showed that the content of total capsaicinoids for the varieties Serrano, Puya, Ancho, Guajillo and Bell pepper were increased with high temperature, while the content of total capsaicinoids and Scoville heat units (SHU) for the varieties De árbol and Jalapeño decreased. However, the pungency values found in this study were higher for all varieties analyzed than in other studies.

The GSTM1null (deletion) and MGMT84 rs12917 (Phe/Phe) haplotype are associated with bulky DNA adduct levels in human leukocytes.

Tobacco smoke and air pollutants contain carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and tobacco specific nitrosamines (TSNA), that are substrates of metabolizing enzymes generating reactive metabolites that can bind to DNA. Variation in the activity of these enzymes may modify the extent to which these metabolites can interact with DNA. We compared the levels of bulky DNA adducts in blood leukocytes from 93 volunteers living in Mexico City with the presence of 13 single nucleotide polymorphisms (SNPs) in genes related to PAH and TSNA metabolism (AhR rs2044853, CYP1A1 rs1048943, CYP1A1 rs1048943, CYP1A1 rs1799814, EPHX1 rs1051740, EPHX1 rs2234922, GSTM1 null, GSTT1 null and GSTP1 rs947894), DNA repair (XRCC1 rs25487, ERCC2 rs13181 and MGMT rs12917) and cell cycle (TP53 rs1042522). (32)P-postlabeling analysis was used to quantify bulky DNA adduct formation. Genotyping was performed using PCR-RFLP. The mean levels of bulky DNA adducts were 8.51±3.66 adducts/10(8) nucleotides (nt) in smokers and 8.38±3.59 adducts/10(8) nt in non-smokers, being the difference not statistically significant. Without taking into account the smoking status, GSTM1 null individuals had a marginally significant lower adduct levels compared with GSTM1 volunteers (p=0.0433) and individuals heterozygous for MGMT Leu/Phe had a higher level of bulky adducts than those who were homozygous wild type (p=0.0170). A multiple regression analysis model showed a significant association between the GSTM1 (deletion) and MGMT rs12917 (Phe/Phe) haplotype and the formation of DNA adducts in smokers (R(2)=0.2401, p=0.0215). The presence of these variants conferred a greater risk for higher adduct levels in this 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.

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.

Polymorphism of CYP1A1*2C, GSTM1*0, and GSTT1*0 in a Mexican Mestizo population: a similitude analysis.

Cytochrome 1A1 (CYP1A1), glutathione transferase M1 (GSTM1), and glutathione transferase T1 (GSTT1) catalyze the bioactivation and detoxification of a wide variety of xenobiotic compounds that are mutagenic and/or carcinogenic (e.g., polycyclic aromatic hydrocarbons). Genetic polymorphisms of these metabolizing enzymes have been shown to affect individual susceptibility to environmental carcinogenic compounds. Although several studies have been published on the relationship between CYP1A1*2C, GSTM1*0, or GSTT1*0 polymorphism and cancer, not all findings can be extrapolated to other populations because of interethnic variability. Here, we investigate the frequency of CYP1A1*2C, GSTM1*0, or GSTT1*0 in a sample of Mexican Mestizos. We find that the frequency of GSTM1*0 is 0.335, that of GSTT1*0 is 0.121, and that of GSTM1*0 + GSTT1*0 is 0.023. The frequency of CYP1A1*2C is 0.54. Similitude analysis sets the Latin American populations in a common cluster near the Asian population, suggesting that the CYP1A1*2C polymorphism may have originated from this population and suffered a founder effect in the American population. Analysis of CYP1A1*2C, GSTM1*0, and GSTT1*0 haplotypes reveals that 35% of the population has some combination of risk genotypes. Taken together, these results point to a high susceptibility of the Mexican Mestizo population to the effects of environmental carcinogens.