To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers.
Multicentric population-based case-control study (MCC-Spain) ...conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region. Dietary intake was collected using a validated food frequency questionnaire. Foods and drinks were categorized according to their degree of processing based on the NOVA classification. Unconditional multivariable logistic regression was used to evaluate the association between ultra-processed food and drink consumption and colorectal, breast, and prostate cancer.
In multiple adjusted models, consumption of ultra-processed foods and drinks was associated with a higher risk of colorectal cancer (OR for a 10% increase in consumption: 1.11; 95% CI 1.04–1.18). The corresponding odds for breast (OR 1.03; 95% CI 0.96–1.11) and prostate cancer (OR 1.02; 95% CI 0.93–1.12) were indicative of no association.
Results of this large population-based case-control study suggest an association between the consumption of ultra-processed foods and drinks and colorectal cancer. Food policy and public health should include a focus on food processing when formulating dietary guidelines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
•Cobalt and ferritin levels were negatively associated in 4-year-old children.•This association is consistent with a common absorption mechanism for Co and Fe.•Low iron supply may influence absorption of cobalt in blood.•Higher cobalt concentrations were found in anemic children.•Some diet components and traffic pollution showed positive associations with Co.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in ...risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69.
Methods
We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase–control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method.
Results
TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10–0.89), as were intermediate (OR 0.18 IC 0.07–0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03–0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08–2.36; OR 1.48 IC 1.09–2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15–2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22–2.11) and HER2+ (OR 1.59 IC 1.03–2.45) tumors.
Conclusion
Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to ...low birthweight.
DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach.
Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy false discovery rate (FDR) < 0.05. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight.
We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome.
Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a ...genome-wide investigation in the International Lung Cancer Consortium (ILCCO).
Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression-based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (
= 887).
One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis HR = 1.71 (1.41-2.07),
= 3.60 × 10
, and altered mRNA expression of
in lung tissue (GTEx,
= 9.40 × 10
; Lung eQTL dataset,
= 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (
< 10
) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including
at 1p36.13 and
at 9q34.3. One locus encoding
at 4p14 showed associations in both European HR = 0.50 (0.38-0.66),
= 6.92 × 10
and Japanese populations HR = 0.79 (0.67-0.94),
= 0.007.
Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants.
We identified one locus near
at genome-wide level and several potential prognostic genes with
-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.
Background: The fetus depends on maternal thyroid hormones during pregnancy for normal brain development. Little is known about the effects of subclinical hypothyroidism and mild hypothyroxinemia ...during pregnancy on neurodevelopment of the child. Methods: We evaluated a population-based birth cohort in Spain. A total of 1761 children and their mothers were included in the main analyses. Serum levels of free thyroxine and thyrotropin were measured in pregnant women. Mental and psychomotor development of their children was assessed using the Bayley Scales of Infant Development during the second year of life. Results: Low free thyroxine levels (<5th percentile) and selfreported prepregnancy thyroid disorder without medical treatment were associated with a decrease of mental scores (Beta = -3.4 95% confidence interval= -6.7 to -0.2) and -5.5 -8.9 to -2.0, respectively). No association between thyrotropin levels and mental scores or psychomotor scores was observed. Conclusions: Low free thyroxine levels in healthy pregnant women are related to a moderate delay in child neurodevelopment. The impairment is similar in magnitude to that observed in mothers with untreated prepregnancy thyroid disorder. The value of screening pregnant women for thyroid function requires further assessment, particularly in mildly iodine-deficient areas.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association ...between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables.
We conducted a hospital‐based case‐control study of bladder cancer in Spain (1998–2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940–2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview.
Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤5mg/L were 1.2 (0.7–2.0) for >5–10mg/L and 1.1 (0.6–1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9–2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4–1.0) for >8 vs. ≤4mg/day. Adjustment for several covariables showed similar results to crude analyses.
Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed.
•Long-term residential and ingested nitrate levels in drinking water were estimated.•Mean residential levels ranged from 2.1mg/L to 12.0mg/L among regions.•Higher risk suggested only for subjects with highest residential levels.•Protective ORs with ingested nitrate may be confounded by water intake.•Endogenous nitrosation factors (e.g. vitamin C intake) did not modify the results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Inflammation provides a substrate for mechanisms that underlie the association of maternal diet during pregnancy with Attention Deficit-Hyperactivity Disorder (ADHD) symptoms in childhood. However, ...no previous study has quantified the proinflammatory potential of maternal diet as a risk factor for ADHD. Thus, we evaluated the association of maternal dietary inflammatory index (DII
®
) scores during pregnancy with ADHD symptoms in 4-year-old children born in two Mediterranean regions. We analyzed data from two population-based birth cohort studies—INMA (Environment and Childhood) four subcohorts in Spain (
N
= 2097), and RHEA study in Crete (Greece) (
N
= 444). The DII score of maternal diet was calculated based on validated food frequency questionnaires completed during pregnancy (12th and/or 32nd week of gestation). ADHD symptoms were assessed by ADHD-DSM-IV in INMA cohort and by ADHDT test in RHEA cohort, with questionnaires filled-out by teachers and parents, respectively. The associations between maternal DII and ADHD symptoms were analysed using multivariable-adjusted zero-inflated negative binomial regression models in each cohort study separately. Meta-analysis was conducted to combine data across the cohorts for fitting within one model. The DII was significantly higher in RHEA (RHEA = 2.09 1.94, 2.24) in comparison to INMA subcohorts (Asturias = − 1.52 − 1.67, − 1.38; Gipuzkoa = − 1.48 − 1.64, − 1.33; Sabadell = − 0.95 − 1.07, − 0.83; Valencia = − 0.76 − 0.90, − 0.62). Statistically significant reduced risk of inattention symptomatology (OR = 0.86; CI 95% = 0.77–0.96), hyperactivity symptomatology (OR = 0.82; CI 95% = 0.72–0.92) and total ADHD symptomatology (OR = 0.82; CI 95% = − 0.72 to 0.93) were observed with increased maternal DII in boys. No statistically significant associations were observed in girls between maternal DII and inattention, hyperactivity and total ADHD symptomatology. We found reduced risk of ADHD symptomatology with increased DII only in boys. This relationship requires further exploration in other settings.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background: Adequate vitamin D status in mothers during pregnancy may influence the health status of the child later in life. We assessed whether maternal circulating 25-hydroxyvitamin D (25OHD) ...concentrations in pregnancy are associated with risk of lower respiratory tract infections, wheezing, and asthma in the offspring. Methods: Data were obtained from 1724 children of the INfancia y Medio Ambiente (INMA) Project, a population-based birth cohort study. Maternal circulating 25(OH)D concentrations were measured in pregnancy (mean gestational age = 12.6 SD = 2.5 weeks). When the child was age 1 year, parents were asked if their child had a physician-confirmed history of lower respiratory tract infections or a history of wheezing. The questions about wheezing were repeated annually thereafter. Asthma was defined as parental report of doctor diagnosis of asthma or receiving treatment at the age of 4-6 years or wheezing since the age of 4 years. Results: The median maternal circulating 25(OH)D concentration in pregnancy was 29.5 ng/mL (interquartile range, 22.5-37.1 ng/mL). After multivariable adjustment, there was a trend for an independent association between higher levels of maternal circulating 25(OH)D levels in pregnancy and decreased odds of lower respiratory tract infections in offspring (for cohort- and season-specific quartile Q4 vs. Q1, odds ratio = 0.67 95% confidence interval = 0.50-0.90; test for trend, P = 0.016). We found no association between 25(OH)D levels in pregnancy and risk of wheezing at age 1 year or 4 years, or asthma at age 4-6 years. Conclusions: Higher maternal circulating 25(OH)D concentrations in pregnancy were independently associated with lower risk of lower respiratory tract infections in offspring in the first year of life but not with wheezing or asthma in childhood.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective
To assess the impact of passive and active tobacco smoke exposure, both pre‐ and postnatally, on child body mass index (BMI) and overweight.
Methods
Pregnant women were enrolled into the ...Spanish INMA prospective birth cohort during 1997 to 2008. Tobacco smoke exposure was assessed by questionnaire and corroborated by pre‐ and postnatal cotinine measurements. Children were followed up until 4 years in newer subcohorts (N = 1866) and until 14 years in one older subcohort (N = 427). Child age‐ and sex‐specific BMI Z‐scores were calculated, and generalized estimating equations were used to model their relationship with repeated measures of tobacco smoke exposure.
Results
Associations between prenatal passive exposure to tobacco smoke (adjusted β = 0.15, 95% CI: 0.05–0.25) and active maternal smoking (adjusted β = 0.20, 95% CI: 0.08–0.33) and child zBMI up to 4 years were observed. Stronger associations were observed in the older subcohort between both prenatal and child passive smoke exposure and zBMI up to 14 years.
Conclusions
Evidence for an effect of both passive and maternal active smoking on child postnatal growth has been provided. Although residual confounding cannot be completely ruled out, associations were robust to adjustment for a range of lifestyle factors.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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