Diabetes mellitus and serum organochlorine pesticides mixtures in Mexican women.

BACKGROUND: Very recently, it has been reported that exposure to different mixtures of organochlorine pesticides (OCP) is associated with the development of diabetes mellitus (DM). In Mexico, DM is a public health problem that might be related to the historical intense use of OCP. We aimed to evaluate, the association between DM and serum concentrations of OCP mixtures, and identify the main contributors within them. METHODS: We conducted a secondary cross-sectional analysis on the control group from a breast cancer population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We identified 214 self-reported diabetic women and 694 non-diabetics. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We determined 24 OCP and metabolites in serum by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of DM and exposure to multiple OCP, and the contribution of each compound within the mixture. RESULTS: We found a positive adjusted association between DM and an OCP mixture (OR: 2.63, 95%CI: 1.85, 3.74), whose primary contribution arose from p, p'-DDE (mean weight 23.3%), HCB (mean weight 17.3%), trans nonachlor (mean weight 15.4%), o, p'-DDE (mean weight 7.3%), heptachlor epoxide (mean weight 5.9%), oxychlordane (mean weight 4.7%), and heptachlor (mean weight 4.5%). In addition, these OCP along with p, p'-DDT and cis chlordane, were of concern and remained associated when excluding hypertensive women from the analysis (OR 2.55; 95% CI 1.56, 4.18). CONCLUSIONS: Our results indicate, for the first time in a Latin-American population, that the concomitant exposure to multiple OCP is associated with DM. Further research is needed since the composition of OCP mixtures may vary according to regional pesticides use patterns.

Carcinogenic, non-carcinogenic risk, and attributable cases to organochlorine pesticide exposure in women from Northern Mexico.

This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.

Breast cancer and urinary metal mixtures in Mexican women.

Humans are environmentally exposed to many metals throughout their lives. Simultaneous exposure to several metals could result in synergistic or antagonistic toxicological effects among them; however, the information on exposure to mixtures of metals and breast cancer (BC) is scarce. The objective of this report was to compare metals considered human carcinogens, individually and as mixtures, in women with and without BC. This is a secondary analysis of a population-based case-control study that was carried out from 2007 to 2011 in Northern Mexico. A total of 499 histologically confirmed BC cases and 499 controls were included. Information about sociodemographic, lifestyle and reproductive characteristics was obtained by in-person interviews. Urinary concentrations of aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), antimony (Sb), cobalt (Co), molybdenum (Mo), tin (Sn), and vanadium (V) were determined by inductively coupled plasma triple quadrupole. Metal mixtures were identified by principal component analysis with creatinine-corrected metals. Over 90% of subjects had metal measurements above the detection limit except tin (86%) and antimony (78.4%). After adjusting by selected covariables, we observed that the individual urinary concentrations of V, Co, and Mo were lower among cases compared to controls; in contrast to Sn that had higher concentrations. We identified two principal component mixtures with opposite relationships with BC: Cr, Ni, Sb, Al, Pb and Sn (OR = 1.15; CI95% 1.06,1.25) and Mo and Co (OR = 0.56; CI95% 0.49,0.64). This is the first study that identified urinary metal mixtures that differed between women with and without BC. Our results warrant confirmation in further prospective epidemiological studies. In addition, the elucidation of underlying mechanisms of metal interactions on BC risk deserves further research.

Prevalence of type 2 diabetes mellitus in relation to arsenic exposure and metabolism in Mexican women.

BACKGROUND: Experimental studies have shown the diabetogenic potential of inorganic arsenic (iAs); however, the epidemiological evidence is still inconclusive. This could be explained by differences in exposure, metabolism efficiency, nutritional and genetic factors. OBJECTIVE: To evaluate the association between type 2 diabetes mellitus (T2DM) prevalence with arsenic exposure and metabolism, considering one-carbon metabolism nutrient intake and arsenite methyltransferase (AS3MT) polymorphisms. METHODS: From healthy controls of a case control study for female breast cancer in northern Mexico, 227 self-reported diabetic women were age-matched with 454 non-diabetics. Participants were interviewed about dietary, sociodemographic and clinical characteristics. Urinary iAs metabolites were determined by HPLC-ICP-MS, methylation efficiency parameters were calculated, and AS3MT c.860 T > C and c.529-56G > C genotypes were determined. Unconditional logistic regression models were used to evaluate associations. RESULTS: Total arsenic in urine (TAs) ranged from 0.73 to 248.12 µg/L with a median of 10.48 µg/L. In unadjusted analysis, TAs (µg/g) was significantly higher in cases than controls, but not when expressed as TAs (µg/L). Cases had significantly lower urinary monomethylarsonic acid percentage (%MMA), first methylation ratio (FMR), creatinine, and choline and selenium intakes. In multi-adjusted models and in women without HTA history T2DM showed significant positive associations with %iAs and FMR, respectively, and a significant negative association with %DMA. In participants with HTA history there was a marginal positive association (p = 0.08) between T2DM and TAs concentrations (µg/g) without other significant associations. CONCLUSIONS: Our results support an association between T2DM prevalence and iAs metabolism but not with urinary arsenic levels. However, elucidation of the interplay among iAs metabolism, T2DM and HTA merit further studies.

Physical activity, body mass index and arsenic metabolism among Mexican women.

BACKGROUND: In some epidemiological studies, a positive association of body mass index (BMI) with inorganic arsenic (iAs) metabolism parameters (percentage dimethylarsinic acid [%DMA] and secondary methylation index [SMI]) has been found. In iAs metabolism, S-Adenosyl methionine is converted to S-Adenosyl homocysteine. Sedentarism has been associated with a higher risk of hyperhomocysteinemia. Physical activity has shown an inconsistent negative association with BMI. Therefore, our objective was to evaluate whether physical activity is associated to iAs metabolism independently of BMI. METHODS: We performed a cross-sectional secondary analysis on 800 non-diabetic women, ≥18 years, who participated as population controls in a previous study on breast cancer in northern Mexico. Participants were interviewed about physical activity during their lifetime, and their weight and size were obtained. Urinary arsenic metabolites concentrations were determined by high performance liquid chromatography coupled with mass spectrometry. RESULTS: In the study population, total arsenic ranged from 0.71 to 303.29 µg/L, and the lifetime average physical activity from 0 to 788.40 min/week. BMI was significantly and negatively associated with percentage monomethylarsonic acid (%MMA) and primary methylation index (PMI), and positively associated with %DMA, SMI and TMI, respectively. Likewise, physical activity was negatively associated with %iAs and %MMA, and positively associated with %DMA, SMI and TMI. These results remained after BMI was adjusted for physical activity and viceversa. CONCLUSION: This study confirms the relationship between BMI and iAs metabolism parameters and provides new evidence on the association between physical activity and iAs metabolism.

A cumulative index of exposure to endogenous estrogens and breast cancer by molecular subtypes in northern Mexican women.

PURPOSE: To evaluate breast cancer (BC) molecular subtypes association with reproductive characteristics and an index of cumulative exposure to endogenous estrogens (EEI) in Mexican women. METHODS: We performed a study of incident cases and population controls in northern Mexico. We included BC cases with tumor molecular classification in their medical records (n = 509), and classified them as HR+/HER2- (ER+ and/or PR+ and HER2-) (n = 289), HER2+ (HR+ or HR-) (n = 117) or triple negative (TN) (n = 103). We matched controls (n = 1030) by age and place of residence with index cases. Women were interviewed about their reproductive history, from which the EEI was developed. We used logistic regression models to estimate BC molecular subtypes associations with reproductive characteristics and EEI. RESULTS: The EEI was higher in all subtypes compared to controls (Median HR+/HER2- 27.25, HER2+ 26.8, TN 24.2 vs. controls 22.8 years, p < 0.05), and was associated with HR+/HER2- (ORT3 vs. T1 = 2.58, 95% CI 1.77-3.55, p-trend < 0.001) and HER2+ (ORT3 vs. T1 = 4.17, 95% CI 2.15-8.08, p-trend < 0.001) BC. Additionally, HR+/HER2- tumors were positively associated with age at first pregnancy and age at menopause, and negatively with age at menarche, parity and breastfeeding. The HER2+ subtype was associated in the same direction as HR+/HER2- tumors with all the reproductive characteristics except for age at menarche. TN tumors were negatively associated with parity and breastfeeding. CONCLUSION: Endogenous estrogens exposure throughout Mexican women reproductive life may contribute to the development of all but TN BC, however, these findings should be confirmed in other Hispanic populations.

Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women.

BACKGROUND: Previously we reported that inorganic arsenic (iAs) methylation capacity was associated with breast cancer (BC). BC risk factors may vary according to immunohistochemical subtype. Here we explored the relationships between the capacity to methylate iAs and the risk of BC by subtype. METHODS: A population-based case-control study was performed in northern Mexico. Patients with available information about BC subtypes (n = 499) were age-matched with healthy controls. Sociodemographic, reproductive, and lifestyle characteristics were obtained. Tumor marker information was obtained from medical records. Cases were classified as HR+ [estrogen receptor (ER+) and/or progesterone (PR+), and human epidermal growth factor receptor 2 (HER2-)], HER2+, or triple negative (TN). Urinary arsenic species were determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and methylation capacity parameters calculated. Conditional logistic regression models were used to estimate BC risk by subtypes. RESULTS: Urinary total arsenic varied from 0.60 to 303.29 µg/L. A significant positive association was found between % monomethylarsonic acid (%MMA) and HR + BC: one percent increase resulted in OR%MMA continuous = 2.73, 95% CI: 1.48, 5.05), and this association remained even when %iAs or % dimethylarsinic acid (%DMA) were added to the models with %MMA. MMA/iAs was positively associated with HR + BC (ORMMA/iAs continuous = 2.03, 95% CI: 1.33-3.10). A significant negative association was observed between DMA/MMA and HR + BC (ORDMA/MMA continuous = 0.43, 95% CI: 0.26, 0.71). MMA/iAs was positively associated with TN BC (OR MMA/iAs continuous = 4.05; 95% CI: 1.63, 10.04). CONCLUSION: Altered iAs methylation capacity resulting in higher %MMA was associated with HR+ and TN BC but not with HER2+. MMA is the iAs metabolite more likely to be related to BC. Further research is needed to confirm these results and elucidate the underlying biological mechanisms.

Arsenic exposure in northern Mexican women.

OBJECTIVE: To describe interindividual metabolism variations and sociodemographic characteristics associated to urinary arsenic, and to estimate the arsenic contamination in water from urinary total arsenic (TAs). MATERIALS AND METHODS: Women (n=1 028) from northern Mexico were interviewed about their sociodemographic characteristics and their urinary concentrations of arsenic species were measured by liquid chromatography. Inorganic arsenic (iAs) in water was estimated from urinary TAs. RESULTS: Women were 20-88 years old. TAs in urine ranged from p10=3.41 to p90=56.93 µg/L; 74% of women had levels >6.4 µg/L. iAs in water varied from p10=3.04 to p90=202.12 µg/L; 65% of women had concentrations >10 µg/L, and 41%, concentrations >25 µg/L. Large variations in iAs metabolism were observed. TAs was significantly negatively associated with age and schooling, and positively with the state of residence. CONCLUSIONS: Exposure to iAs is an environmental problem in Mexico. Individual variations in metabolism are a challenge to design prevention and control programs.

OBJETIVO: Describir las variaciones interindividuales del metabolismo y las características sociodemográficas asociadas con el arsénico urinario, así como estimar su contaminación en el agua. MATERIAL Y MÉTODOS: Se entrevistó a 1 028 mujeres del norte de México; por cromatografía de líquidos se midieron los metabolitos urinarios de arsénico y, a partir de ellos, se estimó la concentración en agua. RESULTADOS: Las mujeres tuvieron 20-88 años. El arsénico urinario varió de p10=3.41 a p90=56.93 µg/L; 74% de las mujeres tuvieron niveles >6.4 µg/L. El arsénico en agua varió de p10=3.04 a p90=202.12 µg/L; 65% de las mujeres tenían concentraciones >10 µg/L, y 41%, >25 µg/L. Se observaron amplias variaciones en el metabolismo del arsénico. El arsénico urinario se asoció negativamente con la edad y escolaridad, y positivamente con el estado de residencia. CONCLUSIONES: La exposición a arsénico es un problema ambiental en México. Las variaciones individuales en su metabolismo son un desafío para diseñar programas de prevención y control.

Effects of ALAD genotype on the relationship between lead exposure and anthropometry in a Cohort of Mexican children.

OBJECTIVES: Lead exposure is associated with children's growth, but this relationship may depend on the presence of susceptibility factors, including genetic variation. Blood lead levels (BLL) differ by ALAD (aminolevulinic acid dehydratase) genotype. We investigated the association between BLL and growth in Mexican first-graders with different ALAD genotypes. METHODS: Children between the ages of 6-8 years (n = 602) attending first grade in schools within the vicinity of a metal foundry in Torreón, Mexico were enrolled into a randomized controlled trial (RCT) testing the efficacy of iron and/or zinc supplementation on blood lead levels (BLL) and cognition. BLL and anthropometry were assessed at baseline (height, height-for-age z-score (HAZ), knee height, head circumference), after 6 (head circumference) and 12 months (height, HAZ, knee height). Children with ALAD1-1 and ALAD1-2/2-2 were compared. The study sample included 538 and 470 participants who had complete data at baseline and follow-up, respectively. Separate multivariable linear regression models adjusted for covariates were used to test the association between BLL at baseline and each anthropometric measure. Covariates included age, sex, hemoglobin, crowding, and maternal education. BLL x ALAD genotype interaction term was tested. RESULTS: Median BLL (10.1 µg/dL) did not differ by ALAD genotype. After covariate adjustment, baseline BLL was inversely associated with baseline height, HAZ, and knee height. The association (ß [95% CI]) between BLL and baseline height (-0.38[-0.68, -0.09]), HAZ (-0.07[-0.12, -0.02]) and knee height (-0.14[-0.25, -0.02]), was somewhat stronger in children with ALAD1-2/2-2 than ALAD1-1 (-0.09[-0.16, -0.02], -0.02[-0.03, -0.004] and -0.04[-0.06, -0.01], respectively). No associations between BLL and growth at 6 or 12 months were detected irrespective of ALAD genotype. CONCLUSIONS: BLL was adversely associated with anthropometric measures among Mexican children. ALAD genotype may be a susceptibility factor for the effects of lead on child growth.

Polyunsaturated fatty acids and child neurodevelopment among a population exposed to DDT: a cohort study.

BACKGROUND: Child neurodevelopment has been positively linked to maternal intake of polyunsaturated fatty acids (PUFAs) during pregnancy; however, it is unknown if that relationship persists among populations exposed to environmental neurotoxicants. OBJECTIVE: The aim of this work was to assess whether maternal dietary intake of PUFAs during pregnancy is positively associated with child neurodevelopment, whose mothers were environmentally exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). METHODS: A prospective cohort study with 276 mother-child pairs was performed in Mexico. Neurodevelopment was assessed by Bayley Scales II from children age 1 to 30 months. Dietary PUFAs intake was estimated by Food Frequency Questionnaire at 1st and 3rd trimester of pregnancy. DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the main metabolite of DDT) maternal serum levels were determined by electron capture gas chromatography. Longitudinal multivariate linear mixed-effects analysis, which combines mental (MDI) and motor (PDI) Bayley scales in a single model, were performed. RESULTS: Our results show that in a sample environmentally exposed to DDT, maternal ingestion of DPA during the first trimester of pregnancy was positively associated with MDI (ß = 0.10, 95% CI 0.02, 0.18) in children from 1 to 30 months. Likewise, our results suggest that dietary ALA may be also related to MDI. CONCLUSION: DPA may benefit neurodevelopment even in populations exposed to DDT. Our results strengthen the importance of PUFAs intake during the prenatal period.

Challenges to regulate products containing bisphenol A: Implications for policy.

Bisphenol A (BPA), found in plastics and epoxy resins, is one of the most studied chemicals. BPA is regarded as an endocrine disruptor and has been related to adverse health effects in humans. However, some regulatory agencies around the world have concluded that BPA is safe at current human exposure levels. As the scientific community attempts to settle the debate on BPA's health effects, regulatory agencies have been put into a challenging public health policy situation. The United States has implemented no regulatory actions due to safety concerns, while Europe has used the precautionary principle to guide its regulation in the face of scientific uncertainty. In this paper, we explore the debate surrounding BPA regulation and the possibility for countries to introduce guidelines, using Mexico as an example. Policy change determinants analysis suggest that countries can and should impose regulations on BPA.

El bisfenol A (BPA), presente en plásticos y resinas epoxi, es uno de los químicos más estudiados. Se considera un disruptor endocrino y se ha relacionado con efectos adversos para la salud humana. Algunas agencias regulatorias en el mundo han concluido que el BPA es seguro a los niveles de exposición humana actuales. Mientas la comunidad científica intenta resolver el debate sobre dichos efectos, las agencias regulatorias enfrentan una difícil situación de política pública. Los Estados Unidos de América no han implementado acciones reglamentarias por razones precautorias, mientras que Europa ha utilizado el principio precautorio para guiar su regulación ante la incertidumbre científica. En este documento exploramos el debate que rodea la regulación del BPA y la posibilidad de que los países introduzcan directrices, usando a México como ejemplo. El análisis de los determinantes del cambio de políticas sugiere que los países pueden y deben regular el BPA.

Arsenic methylation capacity in relation to nutrient intake and genetic polymorphisms in one-carbon metabolism.

BACKGROUND: Nutrients and genetic polymorphisms participating in one-carbon metabolism may explain interindividual differences in inorganic arsenic (iAs) methylation capacity, which in turn may account for variations in susceptibility to iAs-induced diseases. OBJECTIVES: 1) To evaluate the association between polymorphisms in five one-carbon metabolism genes (FOLH1 c.223 T > C, MTHFD1 c.1958 G > A, MTHFR c.665 C > T, MTR c.2756 A > G, and MTRR c.66 A > G) and iAs methylation capacity; 2) To assess if previously reported associations between nutrient intake and iAs methylation capacity are modified by those polymorphisms. METHODS: Women (n = 1027) exposed to iAs in Northern Mexico were interviewed. Blood and urine samples were collected. Nutrient dietary intake was estimated using a validated food frequency questionnaire. iAs methylation capacity was calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) measured by high performance liquid chromatography (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped by allelic discrimination. Multivariable linear regression models were used to evaluate if genetic polymorphisms modified the associations between iAs methylation capacity parameters and nutrient intake. RESULTS: The median (min-max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) µg/g creatinine in the study population. Significant interactions for iAs metabolism were only found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an increased vitamin B12 intake, as compared to carriers of wild-type TT. CONCLUSION: Differences in dietary nutrient intake and genetic variants in one-carbon metabolism may jointly influence iAs methylation capacity. Confirmation of these interactions in other populations is warranted.

Iron and Zinc Supplementation Does Not Impact Urinary Arsenic Excretion in Mexican School Children.

OBJECTIVE: To examine the role of iron and zinc in arsenic excretion and metabolism in children. STUDY DESIGN: An analysis of urinary arsenic (UAs) concentrations from a double-blind randomized trial originally testing the efficacy of iron and zinc for lowering blood lead levels in children. A 2 × 2 factorial design was used, with children randomized individually, stratified by sex and classroom, to receive 30?mg ferrous fumarate (n?=?148), 30?mg zinc oxide (n?=?144), iron and zinc together (n?=?148), or placebo (n?=?151). Of the 602 children enrolled, 527 completed the 6-month treatment, and 485 had both baseline and final UAs values. The baseline total UAs concentration ranged from 3.2 to 215.9?µg/L. RESULTS: At baseline, children in the highest tertile of serum ferritin concentration had higher excretion of dimethylarsinic acid (DMA; 1.93?±?0.86%; P?

Arsenic metabolism and cancer risk: A meta-analysis.

OBJECTIVE: To describe the studies that have reported association measures between risk of cancer and the percentage distribution of urinary inorganic arsenic (iAs) metabolites by anatomical site, in non-ecological epidemiological studies. METHODS: Studies were identified in the PubMed database in the period from 1990 to 2015. Inclusion criteria were: non-ecological epidemiological study, with histologically confirmed cancer cases, reporting the percentage distribution of inorganic arsenic (iAs), monomethylated (MMA) and dimethylated (DMA) metabolites, as well as association measures with confidence intervals (CI) between cancer and %iAs and/or %MMA and/or %DMA. A descriptive meta-analysis was performed by the method of the inverse of the variance for the fixed effects model and the DerSimonian and Laird's method for the random effects model. Heterogeneity was tested using the Q statistic and stratifying for epidemiological design and total As in urine. The possibility of publication bias was assessed through Begg's test. RESULTS: A total of 13 eligible studies were found, most of them were performed in Taiwan and focused on skin and bladder cancer. The positive association between %MMA and various types of cancer was consistent, in contrast to the negative relationship between %DMA and cancer that was inconsistent. The summary risk of bladder (OR=1.79; 95% CI: 1.42, 2.26, n=4 studies) and lung (OR=2.44; 95% CI: 1.57, 3.80, n=2 studies) cancer increased significantly with increasing %MMA, without statistical heterogeneity. In contrast, lung cancer risk was inversely related to %DMA (OR=0.58; 95% CI: 0.36, 0.93, n=2 studies), also without significant heterogeneity. These results were similar after stratifying by epidemiological design and total As in urine. No evidence of publication bias was found. CONCLUSION: These findings provide additional support that methylation needs to be taken into account when assessing the potential iAs carcinogenicity risk.

Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area.

BACKGROUND: Dichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy. OBJECTIVE: To evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy. MATERIALS AND METHODS: We analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age ≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models. RESULTS: Thirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH >2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (ß=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis. CONCLUSIONS: Our findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.

CYP1A1, CYP1B1, GSTM1 and GSTT1 genetic variants and breast cancer risk in Mexican women.

OBJECTIVE: To evaluate if variants in the genes CYP1A1 (T3801C and A4889G), CYP1B1 (G119T), GSTM1 (indel) and GSTT1 (indel) are associated with breast cancer (BC) among Mexican women. MATERIALS AND METHODS: 952 incident cases with histologically confirmed BC were matched by age (± 5 years) and zone of residence with 998 healthy population controls. Genetic variants in genes CYP1A1, CYP1B1, GSTM1 and GSTT1were genotyped by allelic discrimination and multiplex PCR. In a subsample of women, 105 markers for ancestry were determined. RESULTS: An increased BC risk, independent of other BC risk factors, was observed among carriers of CYP1B1 G119T genotype (T/T vs. G/G: OR=1.9; 95%CI 1.4-2.5). CONCLUSION: Our results support the existence of genetic susceptibility for BC conferred by CYP1B1 G119T variant among Mexican women.

Sex differences in the reduction of arsenic methylation capacity as a function of urinary total and inorganic arsenic in Mexican children.

Chronic arsenic (As) exposure decreases adult and children's ability to methylate inorganic As (iAs); however, few studies have examined children's sex differences. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids, and calculated the primary (PMI: MMA/iAs) and secondary (SMI: DMA/MMA) methylation capacity indexes in 591 children 6-8 years in Torreón, Mexico. We determined iAs, MMA, and DMA by hydride generation cryotrapping AAS. Lineal regression models estimated associations between methylation capacity and total As (TAs) or iAs. Interactions with sex were tested at p<0.10. Boys had significantly higher TAs levels, (58.4µg/L) than girls (46.2µg/L). We observed negative associations between TAs and PMI (ß=-0.039; p<0.18) and SMI (ß=-0.08; p=0.002) with significant sex differences; PMI reduction was significant in boys (ß=-0.09; p=0.02) but not in girls (ß=0.021; p=0.63), p for interaction=0.06. In contrast, SMI reduction was significantly more pronounced in girls. Furthermore, negative associations PMI (ß=-0.19; p<0.001) and SMI (ß=-0.35; p<0.001) were a function of urinary iAs levels, independently of TAs; however, the reduction in PMI was more pronounced in boys (ß=-0.24; p<0.001; girls ß=-0.15; p<0.001), p for interaction=0.04. A significant negative association was observed between SMI and iAs levels without significant sex differences. TAs and iAs associations with metabolite percentages were in good agreement with those observed with methylation indexes. Our results suggest that iAs plays an important role in reducing As methylation ability and that significant sex differences are present in As metabolism. These differences merit further investigation to confirm our findings and their potential implications for arsenic toxicity in children.

Association between organochlorine pesticide exposure and thyroid hormones in floriculture workers.

Several studies have suggested that exposure to DDT may be related to changes in thyroid hormone levels in animals and humans, even though results across studies are inconsistent. The aim of this study was to assess the association between exposure to p,p'-DDE (a stable metabolite of DDT) and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the States of Mexico and Morelos, Mexico, who were occupationally exposed to pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on socio-demographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Blood and urine samples were collected to determine serum levels of TSH, total T3, total T4, and p,p'-DDE, and metabolites of organophosphate pesticides (OP), respectively. The analysis of the associations between p,p'-DDE levels and thyroid hormone profile adjusting by potential confounding variables including urinary OP metabolites was carried out using multivariate generalized estimating equation (GEE) models. Our results showed that the geometric means of p,p'-DDE levels were 6.17 ng/ml and 4.71 ng/ml in the rainy and dry seasons, respectively. We observed positive associations between the serum levels of p,p'-DDE and those of total T3 (ß=0.01, 95% CI: -0.009, 0.03), and total T4 (ß=0.08, 95% CI:0.03, 0.14) and negative but no significant changes in TSH in male floricultural workers, supporting the hypothesis that acts as thyroid disruptor in humans.

Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women.

INTRODUCTION: Concentrations of inorganic arsenic (iAs) metabolites in urine present intra- and interindividual variations, which are determined not only by the magnitude of exposure to iAs, but also by differences in genetic, environmental and dietary factors. OBJECTIVE: To evaluate whether differences in dietary intake of selected micronutrients are associated with the metabolism of iAs. METHODS: The intake of 21 micronutrients was estimated for 1027 women living in northern Mexico using a food frequency questionnaire. Concentration of urinary metabolites of iAs was determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and the proportion of iAs metabolites was calculated (%iAs, monomethylarsonic acid [%MMA] and dimethylarsinic acid [%DMA]), as well as ratios corresponding to the first (MMA/iAs), second (DMA/MMA) and total methylation (DMA/iAs). RESULTS: After adjustment for covariates, it was found that methionine, choline, folate, vitamin B12, Zn, Se and vitamin C favor elimination of iAs mainly by decreasing the %MMA and/or increasing %DMA in urine. CONCLUSIONS: Our results confirm that diet contributes to the efficiency of iAs elimination. Further studies are needed to assess the feasibility of dietary interventions that modulate the metabolism of iAs and the consequent risk of diseases related to its exposure.

Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women.

OBJECTIVE: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). MATERIALS AND METHODS: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. RESULTS: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. CONCLUSION: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.