Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Spatial distribution of unscheduled hospital admissions for chronic obstructive pulmonary disease in the central area of Asturias, Spain.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major causes of mortality worldwide and also reports high morbidity rates and the global burden COPD has continued to rise over the last several decades. The best-known COPD risk factors are tobacco smoke and air pollution, but genetics, age, sex, and socioeconomic status are additional factors. This study aimed to assess the spatial distribution of unscheduled COPD hospital admissions of men and women in the central area of Asturias during 2016-2018 and identify trends, spatial patterns, or clusters in the area. METHODS: Unscheduled COPD hospital admissions in the central area of Asturias were registered, geocoded, and grouped by census tracts (CTs), age, and sex. Standardized admission ratio, smoothed relative risk, posterior risk probability, and spatial clusters between relative risks throughout the study area were calculated and mapped. RESULTS: The spatial distribution of COPD hospital admissions differed between men and women. For men, high-risk values were located primarily in the northwestern area of the study, whereas for women the cluster pattern was not as clear and high-risk CTs also reached central and southern areas. In both men and women, the north-northwest area included the majority of CTs with high-risk values. CONCLUSIONS: The present study showed the existence of a spatial distribution pattern of unscheduled COPD hospital admissions in the central area of Asturias that was more pronounced for men than for women. This study could provide a starting point for generating knowledge about COPD epidemiology in Asturias.

Arsenic exposure and respiratory outcomes during childhood in the INMA study.

Ingested inorganic arsenic (iAs) is a human carcinogen that is also linked to other adverse health effects, such as respiratory outcomes. Yet, among populations consuming low-arsenic drinking water, the impact of iAs exposure on childhood respiratory health is still uncertain. For a Spanish child study cohort (INfancia y Medio Ambiente-INMA), low-arsenic drinking water is usually available and ingestion of iAs from food is considered the major source of exposure. Here, we explored the association between iAs exposure and children's respiratory outcomes assessed at 4 and 7 years of age (n = 400). The summation of 4-year-old children's urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of iAs exposure (∑As) (median of 4.92 µg/L). Children's occurrence of asthma, eczema, sneeze, wheeze, and medication for asthma and wheeze at each assessment time point (i.e., 4- and 7-year) was assessed with maternal interviewer-led questionnaires. Crude and adjusted Poisson regression models using Generalized Estimating Equation (GEE) were performed to account for the association between natural logarithm transformed (ln) urinary ∑As in µg/L at 4 years and repeated assessments of respiratory symptoms at 4 and 7 years of age. The covariates included in the models were child sex, maternal smoking status, maternal level of education, sub-cohort, and children's consumption of vegetables, fruits, and fish/seafood. The GEE-splines function using Poisson regression showed an increased trend of the overall expected counts of respiratory symptoms with high urinary ∑As. The adjusted expected counts (95% confidence intervals) at ln-transformed urinary ∑As 1.57 (average concentration) and 4.00 (99th percentile concentration) were 0.63 (0.36, 1.10) and 1.33 (0.61, 2.89), respectively. These exploratory findings suggest that even relatively low-iAs exposure levels, relevant to the Spanish and other populations, may relate to an increased number of respiratory symptoms during childhood.

Environmental and dietary determinants of metal exposure in four-year-old children from a cohort located in an industrial area (Asturias, Northern Spain).

Urine samples from four-year-old children located in a heavily industrialized zone in Asturias (Spain) were collected between 2009 and 2012 (n = 334). Vanadium (V; median 54 µg/g creatinine), cobalt (Co; 1.0 µg/g c.), nickel (Ni; 3.8 µg/g c.), copper (Cu; 22 µg/g c.), zinc (Zn; 590 µg/g c.), arsenic (As; 64 µg/g c.), selenium (Se; 49 µg/g c.), molybdenum (Mo; 110 µg/g c.), cadmium (Cd; 0.27 µg/g c.), antimony (Sb; 1.0 µg/g c.), cesium (Cs; 14 µg/g c.), barium (Ba; 2.6 µg/g c.), thallium (Tl; 0.55 µg/g c.) and lead (Pb; 1.9 µg/g c.) were analysed. Comparison with children from other sites showed that this Asturias cohort was characterized by high levels of V, As, Sb, Cs and Tl. The concentrations of Co, Ni, Zn, Cu, Mo, Se, Cd, Ba and Pb were within the range of other cohorts. Terrestrial dietary items were most strongly related to increased urinary concentrations of metals in children, e.g., red meat with Ba and Ni, pasta/cereal with Ni and Zn, sweets with Zn, Co, and Cu, eggs with Mo, Cd, and Cs, and dairy products with Co and Sb. Seafood was the second group of dietary items significantly related to increased metals, e.g., shellfish with Ba, Cs, Pb, and V, fatty fish with As, and lean fish with As and Se. In contrast, higher fruit intake was significantly associated with decreased Cu and Sb, and higher legume intake with decreased Cu, Se and Cs. Higher intakes of other dietary items also led to significant decreases in some metals, such as vegetables and lower concentrations of Se and Mo, and dairy products with decreases in Cu and As. These negative correlations implied very low concentrations of the mentioned metals in these foods. Higher exposure to traffic was associated with higher concentrations of Ba, present in brake components. Children living outside urban areas had higher concentrations of Se. No association of metals with smoking in the family was found.

Geographical Variability in Mortality in Urban Areas: A Joint Analysis of 16 Causes of Death.

The geographical distribution of mortality has frequently been studied. Nevertheless, those studies often consider isolated causes of death. In this work, we aim to study the geographical distribution of mortality in urban areas, in particular, in 26 Spanish cities. We perform an overall study of 16 causes of death, considering that their geographical patterns could be dependent and estimating the dependence between the causes of death. We study the deaths in these 26 cities during the period 1996-2015 at the census tract level. A multivariate disease mapping model is used in order to solve the potential small area estimation problems that these data could show. We find that most of the geographical patterns found show positive correlations. This suggests the existence of a transversal geographical pattern, common to most causes of deaths, which determines those patterns to a higher/lower extent depending on each disease. The causes of death that exhibit that underlying pattern in a more prominent manner are chronic obstructive pulmonary disease (COPD), lung cancer, and cirrhosis for men and cardiovascular diseases and dementias for women. Such findings are quite consistent for most of the cities in the study. The high positive correlation found between geographical patterns reflects the existence of both high and low-risk areas in urban settings, in general terms for nearly all the causes of death. Moreover, the high-risk areas found often coincide with neighborhoods known for their high deprivation. Our results suggest that dependence among causes of death is a key aspect to be taken into account when mapping mortality, at least in urban contexts.

Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort.

Smoking by women is associated with adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, low birth weight, infertility, and prolonged time to pregnancy. Anogenital distance (AGD) is a sensitive biomarker of prenatal androgen and antiandrogen exposure. We investigated the effect of smoking and passive smoke exposure during pregnancy on anogenital distance in offspring at 4 years in the INMA-Asturias cohort (Spain). Women were interviewed during pregnancy to collect information on tobacco consumption, and anogenital distance was measured in 381 children: Anoscrotal distance in boys and anofourchetal distance in girls. We also measured maternal urinary cotinine levels at 32 weeks of pregnancy. We constructed linear regression models to analyze the association between prenatal smoke exposure and anogenital distance and adjusted the models by relevant covariates. Reported prenatal smoke exposure was associated with statistically significant increased anogenital index (AGI), both at week 12 of pregnancy (ß = 0.31, 95% confidence interval: 0.00, 0.63) and at week 32 of pregnancy (ß = 0.31, 95% confidence interval: 0.00, 0.63) in male children, suggesting altered androgenic signaling.

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 µg/L and 0.97 µg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (pint < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (pint < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (pint < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.

Protein-altering germline mutations implicate novel genes related to lung cancer development.

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10-22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.

Urinary cobalt and ferritin in four-years-old children.

Cobalt (Co) is an essential trace element but may cause toxic effects upon occupational or environmental exposure. The present study is aimed to determine the urine concentrations of Co in four years-old children in the INMA-Asturias cohort (Spain) and to assess the factors determining the observed levels. This cohort is located in a heavily industrialized zone with strong potential for metal exposure. Some diet components such as consumption of sweets were meaningfully associated with higher urine Co concentrations. Traffic pollution also showed a noteworthy positive association with Co levels. Family tobacco consumption did not show substantial association with the urine concentrations of this metal in the INMA-Asturias children. A significant inverse association between urine Co and venous blood ferritin was found. Iron deficiency anemic children had significantly higher concentrations of Co than those with normal levels, e.g. median values 1.9 µg/g creatinine and 1.0 µg/g creatinine, respectively. This association could be explained by an increased expression of DMT1, a divalent metal transporter that captures higher levels of iron in deficiency states of this metal. This transporter is non-specific and not only captures iron but also other divalent metals such as Co. The presence of this metal in iron deficiency anemic children may represent an additional disturbing health factor that must be considered during treatment.

Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy.

Importance: Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development. Objective: To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. Design, Setting, and Participants: In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Main Outcomes and Measures: Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Results: Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-µg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 µm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-µg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 µg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. Conclusions and Relevance: The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.

Maternal nut intake in pregnancy and child neuropsychological development up to 8 years old: a population-based cohort study in Spain.

There is scientific evidence on the protective effects of nut intake against cognitive decline in the elderly; however, this effect has been less explored in child neurodevelopment and no studies have explored the potential longitudinal association with nut intake during pregnancy. We aimed to analyze the association of maternal nut intake during pregnancy with child neuropsychological outcomes. We included 2208 mother-child pairs from a population-based birth cohort in four regions of Spain. The follow up settings were during pregnancy (first and third trimesters), birth, 1.5, 5 and 8 years. Neuropsychological examinations were based on Bayley Scales of Infant Development (1.5 years), McCarthy scales of Children's Abilities (5 year), Attention Network Test (ANT, 8 year) and N-Back test (8 year). Nut intake in pregnancy was reported through a validated food frequency questionnaire during the first and the third trimester. Multivariable regressions analyzed associations after controlling for priori selected confounders notably maternal education, social class, body mass index, energy intake, fish intake, omega-3 supplements, alcohol consumption and smoking habits during pregnancy. Children within the highest tertile of maternal nut consumption during first pregnancy trimester (> 32 g/week) had a decrease of 13.82 ms [95% confidence interval (CI) - 23.40, - 4.23] in the ANT-hit reaction time standard error, compared to the first tertile (median 0 g/w). A similar protective association pattern was observed with the other cognitive scores at the different child ages. After correcting for multiple testing using Bonferroni familywise error rate (FWER), Hochberg FWER and Simes false discovery rate, ANT-hit reaction time standard error remained significant. Final model estimates by inverse probability weighting did not change results. Third pregnancy trimester nut intake showed weaker associations. These data indicate that nut intake during early pregnancy is associated with long-term child neuropsychological development. Future cohort studies and randomized clinical trials are needed to confirm this association pattern in order to further extend nutrition guidelines among pregnant women.

Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis.

BACKGROUND: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. METHODS: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. RESULTS: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non-small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. CONCLUSIONS: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. IMPACT: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci.

DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.

Poor mothers, unhealthy children: the transmission of health inequalities in the INMA study, Spain.

BACKGROUND: The health of pregnant women and their fetuses are especially sensitive to socioeconomic conditions. This study analyzes the impact of maternal socioeconomic status (SES), evaluated by occupation and maternal education level, in preterm births (PTBs) and in small for gestational age (SGA) fetuses, considering the effect of the potential mediating factors on the SES and birth outcomes. METHODS: A total of 2497 mother/newborn dyads from the INMA-Spain project were studied. We examined maternal occupation and education in relation to PTB and SGA along with covariate data, using logistic regression analysis. Adjusted models for each of the outcome variables in relation to SES indicators were estimated, considering potential mediating factors. RESULTS: About 4.7% of babies were PTB and 9.7% SGA. Full adjusted logistic regression models showed similar odds ratio (OR) for SGA in both SES indicators. Manual working women or without university studies had higher risk of SGA than their counterpart groups (OR = 1.39% CI = 1.03-1.88 and OR = 1.39% CI = 1.00-2.00, respectively). Likewise, mothers with a manual occupation were at more risk of PTB than those with a non-manual occupation (OR = 1.74 95% CI = 1.13-2.74), but there was no association between education and PTB. Smoking, pre-pregnancy BMI and underweight gain during pregnancy were significantly associated to SGA births. The mother's age, presence of complications and overweight gain during pregnancy were related to PTB. CONCLUSION: The mother's socioeconomic disadvantage was consistently associated with birth outcomes giving rise to intergenerational transmission of health inequalities. Reducing inequalities requires eliminating the upstream causes of poverty itself.

Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity.

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Social Factors Associated with Non-initiation and Cessation of Predominant Breastfeeding in a Mother-Child Cohort in Spain.

Objective The aim of the study was to identify factors associated with non-initiation and cessation of predominant breastfeeding (PBF) in a mother-child cohort from Spain. Materials and Methods The analysis included 2195 mother-infant from birth to 14 months post- delivery recruited between 2004 and 2008. Maternal characteristics were collected during the pregnancy. Lactation data were obtained at 6 and 14 months after delivery. PBF was defined as intake of breast milk plus liquids like juices or water. The PBF cessation was calculated using the date that women started PBF and the date that she reported to start giving infant formula and/or food. The relationship between maternal variables and PBF initiation and cessation was modeled using logistic and Cox proportional hazards regression analysis. Results The prevalence of PBF at hospital discharge was 85.3, 53.4% at 3 months, 46.1% at 4 months and 7.2% at 6 month. Only two women continued PBF at 12 months and none at 14 months. The initiating of PBF was associated with higher levels of maternal education, being a first-time mother and worked in a non-manual occupation. Higher level of physical activity, not smoking and having a healthy BMI, were also positively associated with PBF initiation. PBF cessation was higher in young, obese women, who had had complications during the pregnancy, and who had lower levels of education and smoked. The employment status of women, in week 32 of pregnancy and also in month 14 post-delivery, determined likelihood of PBF cessation. Conclusions Healthier habits and education positively influenced PBF initiation and duration. Decrease in PBF duration rates in Spain can be interpreted in part as a consequence of women returning to work.

Alcohol Consumption and Lung Cancer According to Ile349Val Polymorphism in ADH3 Gene: Beyond the Tobacco Smoking Effect.

Objectives: Smoking is the leading cause of lung cancer. However, several studies have suggested other factors such as alcohol consumption could also play a role through polymorphisms associated with alcohol metabolism. We investigated the association between alcohol consumption and lung cancer according to the Ile349Val polymorphism in the alcohol dehydrogenase 3 ADH3 gene. Methods: We carried out a hospital-based case-control study, a total of 402 incident cases of lung cancer and 383 controls were genotyped for the Ile349Val polymorphism by polymerase chain reaction combined with restriction fragment length polymorphism. Alcohol consumption and other variables were measured using questionnaires in personal interviews. We used multiple logistic regressions to estimate adjusted odd ratios using and 95% confidence intervals. Results: In multivariate analysis, an increased risk of lung cancer was observed for the highest category of alcohol consumption (≥30 g/day), although it does not reach statistical significance (OR=1.60, 95% CI: 0.91-2.83). Besides, an increased risk of lung cancer was observed in the highest category of alcohol consumption for the Ile/Val genotype compared with the Ile/Ile genotype (OR=2.35, 95% CI: 1.04-5.33). Conclusions: This study suggests that beyond smoking consumption, a high consumption of alcohol might increase the risk of lung cancer. No clear association was found between alcohol consumption and lung cancer according to the Ile349Val polymorphism in ADH3 gene.

Effect of alcohol and its metabolites in lung cancer: CAPUA study. / Efecto del alcohol y sus metabolitos en el cáncer de pulmón: estudio CAPUA.

BACKGROUND AND OBJECTIVE: Alcohol and its metabolites play an important role in carcinogenesis. This effect could be modulated by polymorphisms in genes encoding enzymes involved in the metabolism of alcohol and folate. Therefore, we analyzed the effect of alcohol consumption and ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI and MTHFR C677T polymorphisms on the risk of developing lung cancer. PATIENTS AND METHODS: We included 876 lung cancer cases and 840 controls of the CAPUA hospital-based case-control study. Genotyping was performed using the Sequenom MassArray (iPLEX GOLD) technology. RESULTS: An alcohol consumption of 0.1-9.9g/day decreased lung cancer risk (ORadjusted=0.71; 95% CI 0.48-1.05), although statistical significance was not achieved. A consumption≥30g/day of alcohol and≥36PY of tobacco increases lung cancer risk (ORadjusted=26.68; 95% CI 12.69-56.10). On the other hand, a high consumption of vegetables (≥116.65g/day) and fruits (≥233.13g/day) decreases lung cancer risk with an alcohol consumption of 0.1-9.9g/day (ORadjusted=0.52; 95% CI 0.30-0.89; ORadjusted=0.58; 95% CI 0.33-1.03, respectively). An alcohol consumption of 10-29.9g/day in ADH1B 48His allele-carriers increases lung cancer risk (ORadjusted=3.32; 95% CI 1.03-10.70). CONCLUSIONS: Alcohol and polymorphisms in genes involved in the metabolism of alcohol and folate are related to the onset of lung cancer.

Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

[Variations in the diagnostic confirmation process between breast cancer mass screening units]. / Variaciones en el proceso de confirmación diagnóstica entre unidades de cribado poblacional de cáncer de mama.

OBJECTIVE: To analyse variations in the diagnostic confirmation process between screening units, variations in the outcome of each episode and the relationship between the use of the different diagnostic confirmation tests and the lesion detection rate. METHOD: Observational study of variability of the standardised use of diagnostic and lesion detection tests in 34 breast cancer mass screening units participating in early-detection programmes in three Spanish regions from 2002-2011. RESULTS: The diagnostic test variation ratio in percentiles 25-75 ranged from 1.68 (further appointments) to 3.39 (fine-needle aspiration). The variation ratio in detection rates of benign lesions, ductal carcinoma in situ and invasive cancer were 2.79, 1.99 and 1.36, respectively. A positive relationship between rates of testing and detection rates was found with fine-needle aspiration-benign lesions (R(2): 0.53), fine-needle aspiration-invasive carcinoma (R(2): 0 28), core biopsy-benign lesions (R(2): 0.64), core biopsy-ductal carcinoma in situ (R(2): 0.61) and core biopsy-invasive carcinoma (R(2): 0.48). CONCLUSIONS: Variation in the use of invasive tests between the breast cancer screening units participating in early-detection programmes was found to be significantly higher than variations in lesion detection. Units which conducted more fine-needle aspiration tests had higher benign lesion detection rates, while units that conducted more core biopsies detected more benign lesions and cancer.