Differential association between dairy intake patterns and incident prostate cancer: a potential dairy matrix effect.

OBJECTIVE: To evaluate the association between dairy intake patterns and the risk of prostate cancer (PC), and its histological differentiation, among men from Mexico City. METHODS: We analyzed the information from 394 incident PC cases paired by age (± 5 years) with 794 population controls. According to the Gleason score at diagnosis, cases were classified as well- (≤ 6), moderately- (= 7), and poorly differentiated PC (≥ 8). Based on a semiquantitative-food frequency questionnaire and using energy-density approach, we estimated the energy-adjusted daily intake of whole milk, cheese (fresh, Oaxaca, and Manchego), cream, and yogurt. Through a principal component analysis, we identified three dairy intake patterns: whole milk, cheese, and yogurt. The association between each dairy intake pattern and PC was evaluated from independent nonconditional logistic regression models. We also evaluated the mediator role of calcium and saturated fat intake. RESULTS: After adjustment, a high intake of whole milk pattern was associated with a 63% increased risk of PC (ORhigh vs low: 1.63; 95% CI 1.17-2.25, p trend = 0.002); at expenses of moderately (ORhigh vs low: 1.77; 95% CI 1.09-2.85, p trend = 0.015) and poorly differentiated PC (ORhigh vs low: 1.75; 95% CI 1.05- 2.92, p trend = 0.031). The association was mainly mediated by calcium intake (proportion mediated = 1.17; p < 0.01). No associations were found between cream and yogurt intake patterns with risk of PC, and its histological grade. CONCLUSIONS: A differential association of dairy intake patterns with risk of PC, and the poorly differentiated PC, was identified. This association seems to be determined by different dairy matrices and it is mediated by calcium content. Longitudinal studies are needed to confirm these findings and be able to identify other potential mediators in the etiology of PC.

Decreased DNA repair capacity caused by exposure to metal mixtures is modulated by the PARP1 rs1136410 variant in newborns from a polluted metropolitan area.

BACKGROUND: DNA damage caused by exposure to metal mixtures and the potential modulating role of genes involved in DNA repair and the antioxidant response have not been evaluated in newborns. AIM: The aim was to evaluate the association between prenatal exposure to metal mixtures and DNA repair capacity (DRC) in newborns from the Metropolitan Area of Mexico City (MAMC), a heavily polluted area, and the impact of variants in genes involved in DNA repair and the antioxidant response on this association. METHODS: We analyzed cord blood samples obtained at delivery from 125 healthy newborns from the MAMC. Twenty-four elements were determined by inductively coupled plasma mass spectrometry (ICP‒MS), but only 12 (Cu, I, Se, Zn, As, Ba, Cs, Mn, Sb, Sr, Pb, and Ti) were quantified in most samples. DRC was assessed by the challenge-comet assay, and OGG1, PARP1, and NFE2L2 genotyping was performed with TaqMan probes. Metal mixtures were identified and analyzed using principal component analysis (PCA) and weighted quantile sum (WQS) regression. Independent adjusted linear regression models were used to evaluate the associations. RESULTS: A null DRC was observed in 46% of newborns. The metals with the highest concentrations were Mn, Sr, Ti, and Pb. Essential elements showed normal levels. Only the mixture characterized by increased As, Cs, Cu, Se, and Zn levels was inversely associated with DRC. As was the principal contributor (37.8%) in the negative direction in the DRC followed by Ba and Sb, according to the WQS regression. Newborns carrying of the derived (G) allele of the PARP1 rs1136410 variant showed decreased DRC by exposure to some potentially toxic metals (PTMs) (As, Cs, and Ba). CONCLUSION: Prenatal exposure to metal mixtures negatively affected DRC in newborns, and the PARP1 rs1136410 variant had a modulating role in this association.

Late puberty onset and lack of acne during adolescence reduce high-grade prostate cancer at adulthood.

BACKGROUND: The interplay between pubertal events patterns (PEP) and prostate cancer (PCa) remains poorly understood. Therefore, we investigated the association of PEP with the odds of PCa, and PCa histological differentiation in men residents of Mexico city. METHODS: In this case-control study, we analyzed the information of 371 incident prostate cancer cases and 775 controls matched on age (±5 years). High-grade prostate cancer was classified with Gleason score at diagnosis as ≥8. With information related to beard growth, age at maximum height attainment, and acne severity, the k-medoids algorithm was used to identify three mutually exclusive PEP (early, intermediate, and late). This association was evaluated using multivariable nonconditional logistic regression models. RESULTS: Men with late PEP, characterized by age at maximum height attainment at around 23 years and no history of acne, was inversely associated with incident (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.15-0.48, p trend <0.01) and high-grade prostate cancer (OR: 0.24; 95% CI: 0.09-0.59, p trend <0.01). Similar associations were observed even after adjusting by IGF-1 (OR: 0.19; 95% CI: 0.06-0.58) and androgens excretion (OR: 0.21; 95% CI: 0.06-0.66). Only the association between the absence of acne and prostate cancer remained significant after adjustment by these biomarkers. CONCLUSIONS: This study suggests that pubertal characteristics might be helpful in identifying risk groups, among which, secondary prevention strategies could be applied. Also, the results agree with previous work suggesting other potential biological mechanisms involved in the etiology of prostate cancer such as the infectious and inflammatory pathways.

Disparities on prostate cancer survival in Mexico: a retrospective cohort study.

OBJECTIVE: To estimate prostate cancer (PC) survival in Mexico and explore survival disparities according to the marginalization level of residence place. MATERIALS AND METHODS: A nationwide administrative claims database (4 110 men) whose PC treatment was financed by Seguro Popular between 2012-2016, was cross-linked to the National Mortality Registry up to December 2019. Patients were classified according to their oncological risk at diagnosis and the marginalization level of the residence municipality. Cox proportional hazards regression was used to estimate multivariable survival functions. RESULTS: Five-years PC survival (69%; 95%CI: 68,71%) ranged from 72% to 54% at very low and very high marginalization, respectively (p for trend<0.001). The lowest PC survival was observed in men with high-risk PC (47%; 95%CI: 33,66%) residents in very high marginalization municipalities. CONCLUSIONS: Overall, PC survival was lower than that reported in other Latin American countries. The distribution of oncologic risk and survival differences across marginalization levels suggests limited early detection and cancer health disparities.

Association between life-course leisure-time physical activity and prostate cancer.

OBJECTIVE: To evaluate the association between life-course leisure-time physical activity (PA) and prostate cancer (PC) among males living in Mexico City. Materials and meth-ods. Information from 394 incident PC cases and 794 popula-tion controls matched by age (± 5 years), was analyzed. Using leisure-time PA information at different life stages, life-course PA patterns were constructed. The association between PA and PC was estimated using an unconditional logistic regres-sion model. RESULTS: Three life-course PA patterns were identified: low PA (71.0%), moderate PA (22.0%), and high PA (7.0%); this last pattern was characterized by higher levels and consistent PA practice. Compared with inactive males, those in the high PA pattern (OR: 0.50; 95%CI: 0.26-0.93) had significantly lower PC odds. CONCLUSION: Intense and regular PA could reduce the possibility of PC. These results are in accordance with PA World Health Organization rec-ommendations.

Dietary flavonoid patterns and prostate cancer: evidence from a Mexican population-based case-control study.

Flavonoids are a broad group of bioactive compounds with anticarcinogenic effects on the prostate that have been scarcely evaluated in Latin American populations. Our objective was to evaluate the association between dietary patterns of flavonoid intake and prostate cancer (PC) in a population-based case-control study carried out in Mexico City. Based on a semi-quantitative FFQ with a frame reference of 3 years before diagnosis or interview, we used an updated database for estimating the daily intake (mg/d) of flavones, flavonols and flavanols for 395 confirmed incident PC cases and 797 population controls matched by age (± 5 years). Histological PC differentiation was evaluated using the Gleason score at diagnosis. Flavonoid dietary intake patterns (FDIP) were determined through principal component analysis, and their association with PC was estimated using logistic regression models. Three FDIP were identified: gallate pattern (GP) characterised by (-)-epicatechin-3-O-gallate, (-)-epigallocatechin-3-O-gallate and (+)-gallocatechin; luteolin pattern (LP) characterised by luteolin and (-)-epigallocatechin-3-O-gallate; and a mixed pattern (MP) that included (+)-catechin, (-)-epicatechin and quercetin. A higher GP (ORT3 v.T1 = 0·47; 95 % CI 0·33, 0·66) and LP intake (ORT3 v. T1 = 0·39; 95 % CI 0·27, 0·59) were associated with a decreased PC likelihood. In contrast, a higher MP intake (ORT3 v. T1 = 2·32; 95 % CI 1·67, 3·23) increased PC likelihood. The possible differential and synergistic anticarcinogenic role of flavonoid compounds in PC deserves further study.

Language development in children of adolescent mothers by residence area, Ensanut 100k / Desarrollo del lenguaje en hijos e hijas de madres adolescentes por área de residencia, Ensanut 100k.

Objective: To evaluate the association between adolescent pregnancy and language development in children living in socioeconomically vulnerable areas of Mexico. Materials and methods: We estimated the standardized language score of children aged 12-59 months who participated in the Ensanut 100k. Teenage mothers (TM) were those who at delivery was between 12-19 years old. The association was estimated using multivariate linear regression; moreover, we evaluated an interaction between type of mother and place of residence. Results: Children of TM who lived in urban areas had lower standardized language scores than those of adult mothers (ß= -0.33 95%CI: -0.65 a -0.01; p for interaction<0.01). However, book availability and/or mother's support for learning significantly reduce this difference. Conclusions: Sociocultural pressures towards TM in urban areas could explain the results; nevertheless, this population could be susceptible to strategies aimed to improve the mother-child relationship and support for learning.

BRCA1 and VDR gene polymorphisms are associated with prostate cancer risk in Mexican men.

Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (ORCC genotype = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (ORG allele = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.

Analysis of testosterone-hydroxylated metabolites in human urine by ultra high performance liquid chromatography-Mass Spectrometry.

Testosterone regulates the male reproductive system and acts directly or indirectly on nearly all systems during fetal, pubertal and adult life. Testosterone homeostasis depends on its synthesis and degradation. The major biotransformation reactions are hydroxylation by different cytochrome P450 (CYP) isoforms. There are no described methods to determine the profile of testosterone-hydroxylated metabolites in human urine. The aim of this study was to develop an analytical method to determine testosterone-hydroxylated metabolites in human urine using UPLC-MS. Seven testosterone-hydroxylated metabolites, androstenedione, and testosterone, were identified by comparison of their tret and positive electrospray ionization (ESI+) data, with those of analytical standards. The method developed is sensitive, specific, repeatable, and precise. Limits of detection and quantitation for all compounds ranged from 1.360 to 13.054 ng/ml and 4.234-39.679 ng/ml, respectively. The percentages of recovery were between 81.2 and 128.8%. The applicability of the analytical method was confirmed by analysis of urine samples obtained from two groups of healthy men (25-30 and 50-75 years old). All analytes were identified with slightly different metabolites profiles in both groups. In conclusion, the UPLC-MS method developed here was validated for the analysis of testosterone-hydroxylated metabolites in human urine.

Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area.

BACKGROUND: Adequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo's or fetus' neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual's susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms. METHODS: We analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR, PON155LM and PON1-108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models. RESULTS: One hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75-1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL: 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ: 1.72; 95%CI 0.93, 3.17) and PON1-108TT (OR TT vs CC: 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms. CONCLUSIONS: These results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.

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.

Prostate cancer screening in low- and middle-income countries: the Mexican case.

Prostate-specific antigen (PSA)-based early detection for prostate cancer is the subject of intense debate. Implementation of organized prostate cancer screening has been challenging, in part because the PSA test is so amenable to opportunistic screening. To the extent that access to cancer screening tests increases in low- and middle-income countries (LMICs), there is an urgent need to thoughtfully evaluate existing and future cancer screening strategies to ensure benefit and control costs. We used Mexico's prostate cancer screening efforts to illustrate the challenges LMICs face. We provide five considerations for policymakers for a smarter approach and implementation of PSA-based screening.

El uso del Antígeno Prostático Específico (APE) para tamizaje para cáncer de próstata sigue siendo tema de amplio debate. La implementación de estrategias de tamiz organizado de cáncer de próstata ha sido un reto en parte porque la prueba de APE se presta para detección oportunista. A medida que aumenta el acceso a las pruebas de detección de cáncer en los países de ingresos bajos y medianos (PIBM), existe la necesidad urgente de evaluar cuidadosamente las estrategias actuales y futuras de detección oportuna de cáncer para garantizar su beneficio y controlar sus costos. Utilizamos los esfuerzos de tamizaje de cáncer de próstata de México para ilustrar los retos para PIBM. Ofrecemos cinco consideraciones dirigidas a tomadores de decisión que permitan contar con estrategias racionales de implementación de tamizaje para cáncer de próstata basado en el uso de APE.

Smoking and prostate cancer: a life course analysis.

BACKGROUND: Inconsistent associations between smoking status and prostate cancer (PC) could be due to exposure assessment error. Reconstructing smoking behaviors over the life course could reduce exposure assessment error. METHODS: As part of a case-control study, we identified 402 incident and histologically confirmed PC cases that were matched by age (±5 years) to 805 population controls. Through direct interview, we obtained information about: age at smoking onset, intensity and frequency of cigarette smoking at different life stages, and smoking cessation age. Smoking status at interview and average smoking index over the lifetime (packs/year) were estimated. Life course smoking patterns were obtained applying the k-means+ method for longitudinal data to the smoking index (pack/year) for each life stage. RESULTS: Two life-course smoking patterns were identified among ever smokers: "pattern A" characterized by males who reported low and constant smoking intensity (87.8%), and "pattern B" (12.2%) males with an initial period of low intensity, followed by an increase during the second period. Compared to never smokers, pattern B was associated with higher poorly differentiated PC, (OR 2.30; 95% CI 1.21-4.38). No association was observed with average smoking index. CONCLUSION: Life course smoking patterns seem to capture the smoking variability during life course and reduce the likelihood of reverse causation. Using this assessment strategy our findings support the potential role of tobacco smoking in PC, particularly poorly differentiated PC. Prospective studies with comprehensive smoking history during the lifetime are needed to confirm these findings.

Child dietary intake of folate and vitamin B12 and their neurodevelopment at 24 and 30 months of age.

OBJECTIVE: To evaluate whether child dietary intake of folate and vitamin B12, is associated with mental and psychomotor development in Mexican children, respectively, at 24 and 30 months of age. MATERIALS AND METHODS: Information about neurodevelopment and dietary intake of folate and vitamin B12 at 24 and 30 months of age among 229 children belonging to a perinatal cohort was analyzed longitudinally. Dietary information was assessed using a semi-quantitative food frequency questionnaire, and neurodevelopment by Bayley Scale of Infant Development II. RESULTS: At 30 months of age, dietary folate intake was marginally associated with increased Mental Development Index (MDI) (b=8.33; 95%CI -0.48, 17.14; p=0.06). Nonsignificant positive associations of vitamin B12 with MDI were found. Psychomotor Development Index (PDI) was not associated with these nutrients. CONCLUSIONS: Dietary folate intake in early childhood may benefit the mental development of children.

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.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study.

OBJECTIVE: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. MATERIALS AND METHODS: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. RESULTS: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 µg/L and 148 µg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (ß=1.34µg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. CONCLUSION.: Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men.

A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (<7), as well as early onset (<60 years) or late onset PC (⩾60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.

Dietary inflammatory index and prostate cancer risk in a case-control study in Mexico.

Recent evidence suggests that a pro-inflammatory diet could be associated with prostate cancer (PC) risk. To evaluate the association between dietary inflammatory index (DII) and PC risk as well as aggressiveness, we conducted a case-control study in Mexico City. Cases were 394 individuals with incident, histologically confirmed PC, who were matched by age (±5 years) with 794 population controls. Dietary information was obtained through a semi-quantitative FFQ with a 3-year frame of reference before diagnosis, for cases, or interview, for controls. On the basis of twenty-eight food parameters, we estimated the energy-adjusted DII (E-DII). According to the Gleason score at diagnosis, PC cases were categorised as high (≥8), moderate (=7) and low (≤6) PC risk. Independent, unconditional logistic regression models adjusted for potential confounders were used to estimate PC risk and PC aggressiveness. There were no significant associations between overall PC risk and E-DII (OR3rd v. 1st tertile 1·18; 95 % CI 0·85, 1·63; P=0·33) or among men with high-risk PC (Gleason≥8) (OR 1·46; 95 % CI 0·88, 2·42; P=0·14). These results do not support the hypothesis that a pro-inflammatory diet is related to PC risk and PC aggressiveness. However, further studies with larger sample sizes, with sufficient statistical power and of varying designs should be conducted to address this hypothesis.

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.

PPARG-LYPLAL1 Multi-Allelic Combination Associated with Obesity and Overweight in Mexican Adolescent Females.

OBJECTIVE: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight. DESIGN: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias. Anthropometric measurements, biochemical parameters, and caloric intake were obtained only in the groups of Mexican female adolescents. RESULTS: A positive genotype-phenotype association was found that involves the multi-allelic combination of three risk alleles (one in PPARG and two in LYPLAL1) with obesity and overweight (OR=3.1, P=.010). This combination also exhibited a significant association with waist circumference (P=.030) and triglycerides levels (P=.030). These associations were supported by a logistic regression analysis adjusted for several confounding variables. CONCLUSIONS: Our data suggest the joint participation of PPARG-LYPLAL1 genes in metabolic disorders development. Hence, these genes could act as potential biomarkers in obesity and overweight. Our findings underscore the complexity of metabolic disorders and provide evidence about the importance of multi-loci analysis to study complex diseases.