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.

Harmonization of indirect reference intervals calculation by the Bhattacharya method.

OBJECTIVES: The aim of this study was to harmonize the criteria for the Bhattacharya indirect method Microsoft Excel Spreadsheet for reference intervals calculation to reduce between-user variability and use these criteria to calculate and evaluate reference intervals for eight analytes in two different years. METHODS: Anonymized laboratory test results from outpatients were extracted from January 1st 2018 to December 31st 2019. To assure data quality, we examined the monthly results from an external quality control program. Reference intervals were determined by the Bhattacharya method with the St Vincent's hospital Spreadsheet firstly using original criteria and then using additional harmonized criteria defined in this study. Consensus reference intervals using the additional harmonized criteria were calculated as the mean of four users' lower and upper reference interval results. To further test the operation criteria and robustness of the obtained reference intervals, an external user validated the Spreadsheet procedure. RESULTS: The extracted test results for all selected laboratory tests fulfilled the quality criteria and were included in the present study. Differences between users in calculated reference intervals were frequent when using the Spreadsheet. Therefore, additional criteria for the Spreadsheet were proposed and applied by independent users, such as: to set central bin as the mean of all the data, bin size as small as possible, at least three consecutive bins and a high proportion of bins within the curve. CONCLUSIONS: The proposed criteria contributed to the harmonization of reference interval calculation between users of the Bhattacharya indirect method Spreadsheet.

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.

Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

BACKGROUND: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. METHODS: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. RESULTS: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. CONCLUSION: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

Transanal Total Mesorectal Excision Versus Anterior Total Mesorectal Excision for Rectal Cancer: A Propensity Score Matched, Population-Based Study in Catalonia, Spain.

BACKGROUND: The clinical value of transanal total mesorectal excision is debated. OBJECTIVE: This study aimed to compare short- and medium-term effects of transanal versus anterior total mesorectal excision for rectal cancer. DESIGN: This was a multicenter retrospective cohort study. SETTING: The study included all Catalonian public hospitals. PATIENTS: All patients receiving transanal or anterior total mesorectal excision (open or laparoscopic) for nonmetastatic primary rectal cancer in 2015 to 2016 were included. MAIN OUTCOME MEASURES: Data on vital status were collected to March 2019. Between-group differences were minimized by applying propensity score matching to baseline patient characteristics. Competing risk models were used to assess systemic and local recurrence along with death at 2 years, and multivariable Cox regression was used to assess 2-year disease-free survival. Results are expressed with their 95% CIs. RESULTS: The final subsample was 537 patients receiving total mesorectal excision (transanal approach: n = 145; anterior approach: n = 392). Median follow-up was 39.2 months (interquartile range, 33.0-45.8). Accounting for death as a competing event, there was no association between transanal total mesorectal excision and local recurrence (matched subhazard ratio 1.28, 95% CI 0.55-2.96). There were no statistical differences in the comparative rate of local recurrence (transanal: 1.77 per 100 person-years, 95% CI 0.76-3.34; anterior: 1.37 per 100 person-years, 95% CI 0.8-2.15) or mortality (transanal: 3.98 per 100 person-years, 95% CI 2.36-6.16; anterior: 2.99 per 100 person-years, 95% CI 2.1-4.07). Groups presented similar 2-year cumulative incidence of local recurrence (4.83% versus 3.57%) and disease-free survival (HR, 1.33; 95% CI 0.92-1.92). LIMITATIONS: We used data only from the public system, the study is retrospective, and data on individual surgeons are not reported. CONCLUSION: These population-based results support the use of either the transanal, open, or laparoscopic approach for rectal cancer in Catalonia. See Video Abstract at http://links.lww.com/DCR/B744.ESCISIÓN MESORRECTAL TOTAL TRANSANAL VERSUS ESCISIÓN MESORRECTAL TOTAL ANTERIOR PARA EL CÁNCER DE RECTO: UN ESTUDIO POBLACIONAL CON EMPAREJAMIENTO DE PUNTAJE DE PROPENSIÓN EN CATALUÑA, ESPAÑA. ANTECEDENTES: Se debate el valor clínico de la escisión mesorrectal total transanal. OBJETIVO: Comparar los efectos a corto y mediano plazo de la escisión mesorrectal total transanal versus anterior para el cáncer de recto. DISEO: Este fue un estudio de cohorte retrospectivo multicéntrico. AJUSTE: El estudio incluyó a todos los hospitales públicos de Cataluña. PACIENTES: Todos los pacientes no metastásicos que recibieron escisión mesorrectal total anterior o transanal (abierta o laparoscópica) por cáncer de recto primario en 2015-16. PRINCIPALES MEDIDAS DE VALORACION: Los datos sobre el estado vital se recopilaron hasta marzo de 2019. Las diferencias entre los grupos se minimizaron aplicando el emparejamiento de puntajes de propensión a las características iniciales del paciente. Se utilizaron modelos de riesgo competitivo para evaluar la recurrencia sistémica y local junto con la muerte a los dos años, y la regresión de Cox multivariable para evaluar la supervivencia libre de enfermedad a dos años. Los resultados se expresan con sus intervalos de confianza del 95%. RESULTADOS: La submuestra final fue de 537 pacientes que recibieron escisión mesorrectal total (abordaje transanal: n = 145; abordaje anterior: n = 392). La mediana de seguimiento fue de 39,2 meses (rango intercuartílico 33,0-45,8). Teniendo en cuenta la muerte como un evento competitivo, no hubo asociación entre la escisión mesorrectal total transanal y la recurrencia local (cociente de subriesgo apareado 1,28, 0,55-2,96). No hubo diferencias estadísticas en la tasa comparativa de recurrencia local (transanal: 1,77 por 100 personas-año, 0,76-3,34; anterior: 1,37 por 100 personas-año, 0,8-2,15) o mortalidad (transanal: 3,98 por 100 personas-año, 2,36-6,16; anterior: 2,99 por 100 personas-año, 2,1-4,07). Los grupos presentaron una incidencia acumulada de dos años similar de recidiva local (4,83% frente a 3,57%, respectivamente) y supervivencia libre de enfermedad (índice de riesgo 1,33, 0,92-1,92). LIMITACIONES: Utilizamos datos solo del sistema público, el estudio es retrospectivo y no se informan datos sobre cirujanos individuales. CONCLUSIONES: Estos resultados poblacionales apoyan el uso del abordaje transanal, abierto o laparoscópico para el cáncer de recto en Cataluña. Consulte. Video Resumen en http://links.lww.com/DCR/B744. (Traducción- Dr. Francisco M. Abarca-Rendon).

Within-subject biological variation estimates using an indirect data mining strategy. Spanish multicenter pilot study (BiVaBiDa).

OBJECTIVES: The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI estimates as gold standard for comparison. METHODS: Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18-75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database. RESULTS: RS2 and RS3 had the best correlation for the CVI estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CVI value was obtained. CONCLUSIONS: Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.

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.

Performance comparison: exome sequencing as a single test replacing Sanger sequencing.

Next generation sequencing tests are used routinely as first-choice tests in the clinic. However, systematic performance comparing the results of exome sequencing as a single test replacing Sanger sequencing of targeted gene(s) is still lacking. Performance comparison data are critically important for clinical case management. In this study, we compared Sanger-sequencing results of 258 genes to those obtained from next generation sequencing (NGS) using two exome-sequencing enrichment kits: Agilent-SureSelectQXT and Illumina-Nextera. Sequencing was performed on leukocytes and buccal-derived DNA from a single individual, and all 258 genes were sequenced a total of 11 times (using different sequencing methods and DNA sources). Sanger sequencing was completed for all exons, including flanking ± 8 bp regions. For the 258 genes, NGS mean coverage was > 20 × for > 98 and > 91% of the regions targeted by SureSelect and Nextera, respectively. Overall, 449 variants were identified in at least one experiment, and 407/449 (90.6%) were detected by all. Of the 42 discordant variants, 23 were determined as true calls, summing-up to a truth set of 430 variants. Sensitivity of true-variant detection was 99% for Sanger sequencing and 97-100% for the NGS experiments. Mean false-positive rates were 3.7E-6 for Sanger sequencing, 2.5E-6 for SureSelect-NGS and 5.2E-6 for Nextera-NGS. Our findings suggest a high overall concordance between Sanger sequencing and NGS performances. Both methods demonstrated false-positive and false-negative calls. High clinical suspicion for a specific diagnosis should, therefore, override negative results of either Sanger sequencing or NGS.

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.

Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking.

Parkinson's disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit ß-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1. Also, aggregates treated with 1 do not provoke neurites' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.

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.