Juan J. Aurrekoetxea

Breast cancer risk and the combined effect of environmental estrogens.

AbstractObjective: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides. Methods: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. Results: The median levels of p,p′-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in >40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00–2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06–3.18) and 1.76 (95% CI 1.04–2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22–9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59–20.21) for those in the highest tertile versus those in the lowest. Conclusions: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.

Occupational risk factors for mycosis fungoides : A European multicenter case-control study.

Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7–16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3–10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2–95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4–59.4) and technical salesmen (OR 8.6, 95% CI = 2.4–30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0–22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0–14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.

Serum levels of polychlorinated dibenzodioxins and dibenzofurans and PCBs in the general population living near an urban waste treatment plant in Biscay, Basque Country.

Levels of PCDD/Fs and dioxin-like PCBs were measured in 16 pooled samples of serum from a total of 322 adults in the general population, to coincide with the start-up of a new municipal solid urban waste treatment plant in Biscay, Basque Country (Spain). Two hundred and eighty-three individual serum samples were also obtained, in which the most common PCBs (28, 52, 101, 118, 138, 153 and 180) were quantified. The samples were taken from four geographical zones: two from the metropolitan area of Bilbao, located less than 2 km from the plant and with high traffic density (Zones E1 and E2), a third located 5 km from the plant in an urban area of Bilbao, also with high traffic density (Zone C1) and the fourth located 20 km from the plant, in a municipality with minimal industrial activity and low traffic density (Zone C2), the latter two being out of the path of the prevailing winds. The median levels of dioxins+furans were similar by zone: E1=24.3, E2=27.3, C1=21.3, C2=18.8 pg g(-1) lipid (p=0.362); by sex: 20.2 vs. 22.6 pg g(-1) lipid in men and women (p=0.328); and by age: 20.8 vs. 21.3 pg g(-1) lipid in subjects aged 20-44 and 45-69 (p=0.505). No detectable levels of PCBs 52 and 101 were found. Significant differences by zone were found only for PCB 180 (p=0.041), with higher values in Zone C2, the zone with the lowest presumed contamination levels. Dioxin-like PCBs (p<0.001) and the most common PCBs (138, 153, 180) (p<0.001) were both statistically associated with age, higher values being found in the 45-69 age group.

Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study

Objectives To estimate the prevalence and factors associated with smoking and misclassification in pregnant women from INMA (INfancia y Medio Ambiente, Environment and Childhood) project, Spain, and to assess the optimal cut-offs for urinary cotinine (UC) that best distinguish daily and occasional smokers with varying levels of second-hand smoke (SHS) exposure. Design We used logistic regression models to study the relationship between sociodemographic variables and self-reported smoking and misclassification (self-reported non-smokers with UC >50 ng/ml). Receiver operating characteristic (ROC) curves were used to calculate the optimal cut-off point for discriminating smokers. The cut-offs were also calculated after stratification among non-smokers by the number of sources of SHS exposure. The cut-off points used to discriminate smoking status were the level of UC given by Youdens index and for 50 and 100 ng/ml for daily smokers, or 25 and 50 ng/ml for occasional smokers. Participants At the third trimester of pregnancy, 2263 pregnant women of the INMA Project were interviewed between 2004 and 2008 and a urine sample was collected. Results Prevalence of self-reported smokers at the third trimester of pregnancy was 18.5%, and another 3.9% misreported their smoking status. Variables associated with self-reported smoking and misreporting were similar, including born in Europe, educational level and exposure to SHS. The optimal cut-off was 82 ng/ml (95% CI 42 to 133), sensitivity 95.2% and specificity 96.6%. The area under the ROC curve was 0.986 (95% CI 0.982 to 0.990). The cut-offs varied according to the SHS exposure level being 42 (95% CI 27 to 57), 82 (95% CI 46 to 136) and 106 ng/ml (95% CI 58 to 227) for not being SHS exposed, exposed to one, and to two or more sources of SHS, respectively. The optimal cut-off for discriminating occasional smokers from non-smokers was 27 ng/ml (95% CI 11 to 43). Conclusions Prevalence of smoking during pregnancy in Spain remains high. UC is a reliable biomarker for classifying pregnant women according to their smoking status. However, cut-offs would differ based on baseline exposure to SHS.

Maternal Smoking During Pregnancy and Fetal Biometry The INMA Mother and Child Cohort Study

In utero tobacco exposure has been associated with fetal growth restriction, but uncertainty remains about critical windows of exposure and specific effects on body segments. In the present study, we aimed to examine the association of maternal smoking with fetal biometry in different stages of pregnancy. The study population comprised 2,478 fetuses from a Spanish birth cohort study that was established between 2003 and 2008. Biparietal diameter, femur length, abdominal circumference, and estimated fetal weight were evaluated at 12, 20, and 34 weeks of gestation. Fetal size and growth were assessed by standard deviation scores adjusted by maternal and fetal characteristics. Maternal smoking was assessed using questionnaire and a sample of urinary cotinine at week 32 of gestation. Associations were estimated using multiple regression analysis. Smokers at week 12 of gestation showed decreased fetal growth as reflected by all growth parameters at 20-34 weeks, leading to a reduced fetal size at week 34. The reduction was greatest in femur length, at -9.4% (95% confidence interval -13.4, -5.4) and least in abdominal circumference, at -4.4% (95% CI: -8.7, -0.1). Fetuses of smokers who quit smoking before week 12 showed reduced growth only in femur length (-5.5; 95% CI: -10.1, -0.9). Dose-response curves for smoking versus fetal growth parameters (abscissa: log2 cotinine) were linear for biparietal diameter and femur length.

Factors associated with second-hand smoke exposure in non-smoking pregnant women in Spain: self-reported exposure and urinary cotinine levels.

The aim of this study was to evaluate the main sources of and sociodemographic factors associated with second-hand smoke (SHS) exposure, assessed both by questionnaire and by urinary cotinine (UC) levels, in non-smoking pregnant women. We conducted a cross-sectional study in pregnant women from 4 different regions in Spain. A total of 1783 non-smoking pregnant women completed a questionnaire about their previous smoking habit and SHS exposure in their 3rd trimester of pregnancy and provided a urine sample for measuring UC levels. We used logistic regression models to assess the relationship between several sociodemographic variables and some potential sources of SHS exposure. In addition, we analysed the association of several sociodemographic variables and the SHS exposure according to UC levels, using Tobit regression analysis. More than half of women (55.5%) were exposed to SHS in their 3rd trimester of pregnancy. The following variables were associated with SHS exposure: having smoked previously, low educational level, and being primiparous. Data collection after the first law banning smoking in public places was associated with lower risk of SHS exposure in restaurants and at work. UC levels were higher among women exposed to more than one source. Having a partner who smoked at home was the source of SHS with the greatest impact on UC levels, followed by having a partner who smoked but not at home, other people smoking in the household, being exposed during leisure time, at work and at restaurants. The most important source of SHS exposure was exposure at home. Prevention of SHS exposure should be addressed not only with pregnant women but also with their families.

Evolution of PCDD/Fs and dioxin-like PCBs in the general adult population living close to a MSW incinerator.

It is well known that municipal solid waste incinerators (MSWI) produce dioxins and furans. The aim of this study was to assess the serum levels of compounds with dioxin-like activity such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like PCBs after the commissioning of a MSWI plant. In 2006 and 2008 serum samples were obtained from 322 and 326 volunteers, respectively, from the general population, some living in the vicinity of the plant and others, as a control group, living further away from the MSWI plant and out of the path of prevailing winds. Samples for sets of 20 individuals, grouped by age and sex, were pooled, obtaining 16 pooled samples per year. No significant differences were observed in PCDD/Fs as a function of area of residence or proximity to the plant over the time of the study, with levels of WHO-TEQ/g lipid nearby and far from the MSWI being 26.9 and 20.0pg, respectively, in 2006 and 20.8 and 26.4pg, respectively, in 2008. There was a significant decrease in the concentration of non-ortho PCBs in the nearby areas, whilst there was a significant increase in the concentration of mono-ortho PCBs, both in the nearby areas and in those further away from the MSWI. Age was significantly associated with PCDD/Fs and dioxin-like PCBs, but sex showed no significant association. Overall, this study found that there was no increase in the levels of compounds with dioxin-like activity in a population living close to an MSWI, in agreement with the literature reviewed, for plants of recent construction using state-of-the-art technology.

Second-hand smoke exposure in 4-year-old children in Spain: Sources, associated factors and urinary cotinine

INTRODUCTION Second-hand smoke exposure (SHS) in children remains as a major pollution problem, with important consequences for childrens health. This study aimed to identify the sources of exposure to SHS among 4-year-old children, comparing self-reports to a urinary biomarker of exposure, and characterize the most important variables related to SHS exposure in this population. METHODS 4-year-old childrens exposure to SHS was assessed by a parental-reported questionnaire and by urinary cotinine (UC) measurements in 1757 participants from 4 different areas of the Spanish INMA (INfancia y Medio Ambiente - Environment and Childhood) Project. The questionnaire about SHS included information about smoking habits at home by household members, and about exposure to SHS in other places including other homes, bars, restaurants or transportation. The association between quantified UC levels (>4ng/ml) and sociodemographic variables and the different sources of SHS exposure was examined using logistic regression. RESULTS Based on parental reports, 21.6% of the children were exposed to SHS at home and 47.1% elsewhere; making a total 55.9% of the children exposed to SHS. In addition, 28.2% of the children whose parents reported being not regularly exposed to SHS had quantified UC values. Children from younger mothers (<34 vs. ≥39.4 y) had a higher odds of exposure to SHS [OR (95% CI): 2.28 (1.70-3.05) per year], as well as from families with a lower educational level [OR secondary: 2.12 (1.69-2.65); primary or less: 2.91 (2.19-3.88)]. The odds of quantifiable UC in children dropped after the smoking ban in public places [OR=0.59 (0.42-0.83)]. Regarding the sources of SHS exposure we observed that quantifiable UC odds was increased in children whose parents smoked at home in their presence [OR mother occasionally: 13.39 (7.03-25.50); mother often: 18.48 (8.40-40.66); father occasionally: 10.98 (6.52-18.49); father often: 11.50 (5.96-22.20)] or in children attending other confined places, mainly other houses where people smoked [OR: 2.23 (1.78-2.80)]. CONCLUSIONS Childrens SHS exposure is nowadays an unresolved major public health problem in Spain. After the ban of smoking in public places health care professionals should put more emphasis to the parents on the importance of controlling the exposure of their children in private spaces.

Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma

Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng·mL−1) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20–50 ng·mL−1) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76–24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.

The association between passive and active tobacco smoke exposure and child weight status among Spanish children

To assess the impact of passive and active tobacco smoke exposure, both pre‐ and postnatally, on child body mass index (BMI) and overweight.