Positive Dose-response Association Research Articles

The association between the serum levels of uric acid and alanine aminotransferase in a population-based cohort.

Elevated serum uric acid levels reflect and also cause both oxidative stress and insulin resistance and are frequently observed in patients with the metabolic syndrome. A strong association exists between the metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to test the association between uric acid and elevated alanine aminotransferase (ALT), as a surrogate for NAFLD, using real-world data. Data used for the cross-sectional study were obtained from Maccabi Healthcare System, a 2-million member health maintenance organization in Israel. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and uric acid between 1997 and 2012. Individuals with secondary liver disease, celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was performed in subjects who were given the diagnosis of fatty liver in their medical records (n = 2628). The study population included 82,608 people (32.5% men, mean age 43.91 ± 10.15 years). There was a significant positive dose-response association between serum uric acid levels and the rate of elevated serum ALT (P for trend <0.001). In multivariable model, controlling for potential confounders, the association between uric acid and elevated ALT persisted (OR = 2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association was maintained in all categories of gender and BMI. Similar results were observed among patients diagnosed with fatty liver (OR = 1.77, 1.22-2.57). Serum uric acid is independently associated with elevated ALT, as a surrogate for NAFLD, and thus may serve as a serum marker for liver damage and should be further investigated as a risk factor for NAFLD.

A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations.

It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.

Don't worry, be happy: cross-sectional associations between physical activity and happiness in 15 European countries.

BackgroundMental health disorders are major contributors to the global burden of disease and their inverse relationship with physical activity is widely accepted. However, research on the association between physical activity and positive mental health outcomes is limited. Happiness is an example of a positive construct of mental health that may be promoted by physical activity and could increase resilience to emotional perturbations. The aim of this study is to use a large multi-country dataset to assess the association of happiness with physical activity volume and its specificity to intensity and/or activity domain.MethodsWe analysed Eurobarometer 2002 data from 15 countries (n = 11,637). This comprised one question assessing self-reported happiness on a six point scale (dichotomised: happy/unhappy) and physical activity data collected using the IPAQ-short (i.e. walking, moderate, vigorous) and four domain specific items (i.e. domestic, leisure, transport, vocation). Logistic regression was used to examine the association between happiness and physical activity volume adjusted for sex, age, country, general health, relationship status, employment and education. Analyses of intensity and domain specificity were assessed by logistic regression adjusted for the same covariates and physical activity volume.ResultsWhen compared to inactive people, there was a positive dose–response association between physical activity volume and happiness (highly active: OR = 1.52 [1.28-1.80]; sufficiently active: OR = 1.29 [1.11-1.49]; insufficiently active: OR = 1.20 [1.03-1.39]). There were small positive associations with happiness for walking (OR = 1.02 [1.00-1.03]) and vigorous-intensity physical activity (OR = 1.03 [1.01-1.05). Moderate-intensity physical activity was not associated with happiness (OR = 1.01 [0.99-1.03]). The strongest domain specific associations with happiness were found for “a lot” of domestic (OR = 1.42 [1.20-1.68]) and “some” vocational (OR = 1.33 [1.08-1.64]) physical activity. Happiness was also associated with “a lot” of leisure physical activity (OR = 1.15 [1.02-1.30]), but there were no significant associations for the transport domain.ConclusionsIncreasing physical activity volume was associated with higher levels of happiness. Although the influence of physical activity intensity appeared minimal, the association with happiness was domain specific and was strongest for “a lot” of domestic and/or “some” vocational physical activity. Future studies to establish causation are indicated and may prompt changes in how physical activity for improving mental health is promoted.

A call for better care: the impact of postnatal contact services on women's parenting confidence and experiences of postpartum care in Queensland, Australia.

BackgroundUniversal postnatal contact services are provided in several Australian states, but their impact on women’s postnatal care experience has not been evaluated. Furthermore, there is lack of evidence or consensus about the optimal type and amount of postpartum care after hospital discharge for maternal outcomes. This study aimed to assess the impact of providing Universal Postnatal Contact Service (UPNCS) funding to public birthing facilities in Queensland, Australia on women’s postnatal care experiences, and associations between amount and type (telephone or home visits) of contact on parenting confidence, and perceived sufficiency and quality of postnatal care.MethodsData collected via retrospective survey of postnatal women (N = 3,724) were used to compare women who birthed in UPNCS-funded and non-UPNCS-funded facilities on parenting confidence, sufficiency of postnatal care, and perceived quality of postnatal care. Associations between receiving telephone and home visits and the same outcomes, regardless of UPNCS funding, were also assessed.ResultsWomen who birthed in an UPNCS-funded facility were more likely to receive postnatal contact, but UPNCS funding was not associated with parenting confidence, or perceived sufficiency or perceived quality of care. Telephone contact was not associated with parenting confidence but had a positive dose–response association with perceived sufficiency and quality. Home visits were negatively associated with parenting confidence when 3 or more were received, had a positive dose–response association with perceived sufficiency and were positively associated with perceived quality when at least 6 were received.ConclusionsFunding for UPNCS is unlikely to improve population levels of maternal parenting confidence, perceived sufficiency or quality of postpartum care. Where only minimal contact can be provided, telephone may be more effective than home visits for improving women’s perceived sufficiency and quality of care. Additional service initiatives may be needed to improve women’s parenting confidence.

Association of quantity and duration of smoking with erectile dysfunction: a dose-response meta-analysis.

Some original studies and a recent meta-analysis suggested that smoking could be associated with the risk of erectile dysfunction (ED), but the dose-response relationship between them was unclear. The aim of this study was to investigate the potential association between quantity and duration of smoking and the risk of ED. We conducted a literature search of PubMed, Embase, Web of Science, and Scopus from these databases' inception through March 2014 for observational epidemiological studies examining the association between smoking and risk of ED. Random-effects meta-analyses were used to combine the results of included studies. Quantitative review of published observational epidemiological studies on the association between smoking and risk of ED was the main outcome measure. One cohort study and nine cross-sectional studies were eligible for inclusion in the meta-analysis (50,360 participants and 12,218 cases with ED). No evidence of a curve linear association was observed between smoking and risk of ED. The summary odds ratio of ED for an increase of 10 cigarettes smoked per day was 1.14 (95% confidence interval 1.09 to 1.18), with moderate heterogeneity (P = 0.061, I(2) = 44.7%). For an increment of 10 years of smoking, the combined odds ratios of ED was 1.15 (95% confidence interval 1.10 to 1.19), without substantial heterogeneity (P = 0.522, I(2) = 0.0%). Evidence from observational studies suggests that there is a positive dose-response association between quantity and duration of smoking and risk of ED.

Urinary concentrations of bisphenol a and their association with indicators of implantation in IVF couples

Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastics and epoxy resins found in numerous consumer products and lead to human exposure. There was a report suggesting positive linear dose-response association between BPA urinary concentrations and implantation failure in women undergoing in vitro fertilization (IVF) (1 , 2 , 3). We evaluated the association of female and male urinary BPA concentrations with various indicators of IVF.

Effects of childhood abuse on adult obesity: a systematic review and meta-analysis.

Controversy exists surrounding the role of childhood abuse in obesity development. This is a meta-analysis of observational studies on the role of childhood abuse in adult obesity. Systematic searches of PubMed, PsycInfo, Medline and CINAHL resulted in 23 cohort studies (4 prospective, 19 retrospective) with n=112,708 participants, containing four abuse types (physical, emotional, sexual, general). Four studies reported dose-response effects. A random effects model was used to quantify effect sizes, meta-regression/subgroup analysis for identifying potential moderating variables and Egger's test for publication bias. Adults who reported childhood abuse were significantly more likely to be obese (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.24-1.45, P<0.001). All four types of abuse were significantly associated with adult obesity: physical (OR: 1.28, 95% CI: 1.13-1.46), emotional (OR: 1.36, 95% CI: 1.08-1.71), sexual (OR: 1.31, 95% CI: 1.13-1.53) and general abuse (OR: 1.45, 95% CI: 1.25-1.69). Severe abuse (OR: 1.50, 95% CI: 1.27-1.77) was significantly more associated with adult obesity (P=0.043) compared with light/moderate abuse (OR: 1.13, 95% CI: 0.91-1.41). We found no significant effects of study design (prospective vs. retrospective, P=0.07), age (P=0.96) or gender (P=0.92). Publication bias was evident (Egger's test P=0.007), but effect sizes remained statistically significant in sensitivity analyses. Childhood abuse was clearly associated with being obese as an adult, including a positive dose-response association. This suggests that adverse life experiences during childhood plays a major role in obesity development, potentially by inducing mental and emotional perturbations, maladaptive coping responses, stress, inflammation and metabolic disturbances.

Association between riding with an impaired driver and driving while impaired.

To examine the association between driving while alcohol/drug impaired (DWI) and the timing and amount of exposure to others' alcohol/drug-impaired driving (riding while impaired [RWI]) and driving licensure timing among teenage drivers. The data were from waves 1, 2, and 3 (W1, W2, and W3, respectively) of the NEXT Generation Study, with longitudinal assessment of a nationally representative sample of 10th graders starting in 2009-2010. Multivariate logistic regression was used for the analyses. Teenagers exposed to RWI at W1 (adjusted odds ratio [AOR] = 21.12, P < .001), W2 (AOR = 19.97, P < .001), and W3 (AOR = 30.52, P < .001) were substantially more likely to DWI compared with those reporting never RWI. Those who reported RWI at 1 wave (AOR = 10.89, P < .001), 2 waves (AOR = 34.34, P < .001), and all 3 waves (AOR = 127.43, P < .001) were more likely to DWI compared with those who never RWI. Teenagers who reported driving licensure at W1 were more likely to DWI compared with those who were licensed at W3 (AOR = 1.83, P < .05). The experience of riding in a vehicle with an impaired driver increased the likelihood of future DWI among teenagers after licensure. There was a strong, positive dose-response association between RWI and DWI. Early licensure was an independent risk factor for DWI. The findings suggest that RWI and early licensure could be important prevention targets.

Associations Between Birth Characteristics and Eating Disorders Across the Life Course: Findings From 2 Million Males and Females Born in Sweden, 1975–1998

Birth characteristics predict a range of major physical and mental disorders, but findings regarding eating disorders are inconsistent and inconclusive. This total-population Swedish cohort study identified 2,015,862 individuals born in 1975-1998 and followed them for anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified until the end of 2010. We examined associations with multiple family and birth characteristics and conducted within-family analyses to test for maternal-level confounding. In total, 1,019 males and 15,395 females received an eating disorder diagnosis. Anorexia nervosa was independently predicted by multiple birth (adjusted hazard ratio = 1.33, 95% confidence interval: 1.15, 1.53) for twins or triplets vs. singletons) and lower gestational age (adjusted hazard ratio = 0.96, 95% confidence interval: 0.95, 0.98) per extra week of gestation, with a clear dose-response pattern. Within-family analyses provided no evidence of residual maternal-level confounding. Higher birth weight for gestational age showed a strong, positive dose-response association with bulimia nervosa (adjusted hazard ratio = 1.15, 95% confidence interval: 1.09, 1.22, per each standard-deviation increase), again with no evidence of residual maternal-level confounding. We conclude that some perinatal characteristics may play causal, disease-specific roles in the development of eating disorders, including via perinatal variation within the normal range. Further research into the underlying mechanisms is warranted. Finally, several large population-based studies of anorexia nervosa have been conducted in twins; it is possible that these studies considerably overestimate prevalence.

Egg consumption and risk of GI neoplasms: dose–response meta-analysis and systematic review

Previous epidemiological studies on egg consumption and the risk of gastrointestinal (GI) neoplasms suggest a positive association; however, data are limited and the evidence remains controversial. This study aims to investigate and quantify the potential dose-response relationship with an evaluation of cancer site-specific differences. Relevant studies were identified after the literature search via electronic databases until January 2014. Subgroup analysis for serving portions was performed using two standardized classification methods: (1) less than 3, or 3 or more eggs per week; (2) less than 3, 3-5, or more than 5 eggs per week. Method two excludes studies that only reported consumption frequency. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random-effects model. Thirty-seven case-control and seven cohort studies were included for meta-analysis, which contained a total of 424,867 participants and 18,852 GI neoplasm cases. The combined odds ratio (OR) was calculated to 1.15 (95% CI 1.09-1.22; p value heterogeneity <0.001), showing only a slight increase in risk. The correlation was stronger for colon cancers 1.29 (95% CI 1.14-1.46; p value heterogeneity <0.22). Dose-response analysis revealed similar results with stratification methods, and the ORs for an intake of <3 and ≥3 eggs per week were 1.14 (95% CI 1.07-1.22; p value heterogeneity = 0.38) and 1.25 (95% CI 1.14-1.38; p value heterogeneity = 0.25), respectively. With method 2, the ORs for an intake of <3, 3-5, and >5 eggs per week were 1.13 (95% CI 1.06-1.21; p value heterogeneity = 0.25), 1.14 (95% CI 1.01-1.29; p value heterogeneity = 0.06), and 1.19 (95% CI 1.01-1.39; p value heterogeneity <0.001), respectively. This study provides evidence that egg consumption is associated with a positive dose-response association with the development of GI neoplasms.

Helicobacter pylori Protein–Specific Antibodies and Risk of Colorectal Cancer

There is biologic plausibility as to why infection with Helicobacter pylori, the leading cause of gastric cancer, may also increase the risk of colorectal cancer, but the epidemiologic findings have been inconsistent. We assessed the association of H. pylori protein-specific infection and colorectal cancer risk in the prospective cohort, the Southern Community Cohort Study. Multiplex serology was used to measure antibodies to 15 H. pylori proteins in prediagnostic blood among 188 incident colorectal cancer cases and 370 controls matched by age, race, sex, and blood collection timing. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). Overall H. pylori prevalence was not associated with colorectal cancer risk (OR, 1.03; 95% CI, 0.59-1.77). However, seropositivity to any of five specific H. pylori proteins (VacA, HP231, HP305, NapA, and HcpC) was associated with a significant 60% to 80% increase in odds of risk. These associations became even stronger when limited to colon cancer risk, particularly for the known H. pylori toxin VacA (OR, 2.24; 95% CI, 1.22-4.11), including a significant, positive dose-response association by VacA antibody levels in quartiles (P < 0.05). Associations with VacA seropositivity were especially strong for early-onset and late-stage cancers. The findings raise the hypothesis that individuals with high levels of antibodies to specific H. pylori proteins may be at higher risk of colon cancer. Further investigation of the H. pylori-colorectal cancer association is warranted to determine the possibility of protein-specific antibody levels as a risk biomarker.

PL03 Associations between Birth Characteristics and Eating Disorders Across the Life Course: Findings from two Million Males and Females Born in Sweden 1975-1998

BackgroundRecent years have seen considerable interest in the developmental origins of eating disorders (ED) but results have been conflicting, perhaps reflecting low power in many studies. Limited power has also...

Sodium intake from various time frames and incident hypertension among Chinese adults.

Although it is clear that there are short-term effects of sodium intake on blood pressure, little is known about the most relevant timing of sodium exposure for the onset of hypertension. This question can be addressed only in cohorts with repeated measures of sodium intake. Using up to seven measures of dietary sodium intake and blood pressure between 1991 and 2009, we compared the association of baseline, mean, and most recent sodium intake with incident hypertension, in 6578 adults enrolled in the China Health and Nutrition Survey (age 18 to 65 years and free of hypertension at baseline). We used survival methods that account for the interval-censored nature of this study and inverse-probability weights to generate adjusted survival curves and time-specific cumulative risk differences; hazard ratios were also estimated. Baseline sodium intake was not associated with incident hypertension. For the mean and most recent measures, the probability of hypertension-free survival was the lowest among those with the highest sodium intake compared with all other intake groups across the entire follow-up. In addition, the most recent sodium intake had a positive dose-response association with incident hypertension (risk difference at 11 years of follow-up = 0.04 [95% confidence interval = 0.00 to 0.08], 0.06 [0.02 to 0.11], 0.18 [0.12 to 0.24], and 0.20 [0.12 to 0.27] for the second to fifth sodium-intake groups compared with the lowest group, respectively). We found that, among the various time frames, the most recent exposure to sodium was most strongly associated with incident hypertension.

Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies

Epidemiologic findings concerning the associations between intakes of heme iron and zinc and colorectal cancer (CRC) incidence yielded conflicting results. We aimed to investigate the associations by performing a meta-analysis of prospective studies. We conducted a literature search on PubMed and EMBASE databases up to December 2012 to identify the prospective studies that investigated the relationships between heme iron or zinc intake and risk of CRC. We also reviewed the bibliographies of the retrieved articles to identify additional studies. We used a random-effects model to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs). Eight studies on heme iron intake and six studies on zinc intake met the inclusion criteria. The summary RR of CRC for the highest versus the lowest intake was 1.14 (95 % CI = 1.04-1.24) for heme iron and 0.83 (95 % CI = 0.72-0.94) for zinc, respectively. The observed associations were not significantly modified by subsites within the colorectum, sex, geographic area, study duration, the number of cases, or the range of intakes. In the dose-response analyses, the summary RR of CRC was 1.11 (95 % CI = 1.03-1.18) for heme iron intake of 1 mg/day, and 0.86 (95 % CI = 0.78-0.96) for zinc intake of 5 mg/day, respectively. There was little evidence of publication bias. This meta-analysis suggests a significant positive dose-response association of heme iron intake and a significant inverse dose-response association of zinc intake with risk of CRC.

Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals

At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60,883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.

Childhood Abuse and Age at Menarche

Physical and sexual abuse are prevalent social hazards. We sought to examine the association between childhood physical and sexual abuse and age at menarche. Among 68,505 participants enrolled in the Nurses' Health Study II, we investigated the association between childhood physical abuse and sexual abuse and menarche before age 11 years (early) or after age 15 years (late) using multivariate logistic regression analysis, mutually adjusting for both types of abuse. Fifty-seven percent of respondents reported some form of physical or sexual abuse in childhood. We found a positive dose-response association between severity of sexual abuse in childhood and risk for early menarche. Compared with women who reported no childhood sexual abuse, the adjusted odds ratio (AOR) for early menarche in women who reported childhood sexual abuse was 1.20 (95% confidence interval [CI]: 1.10, 1.37) for sexual touching and 1.49 (95% CI: 1.34, 1.66) for forced sexual activity. Severe physical abuse predicted early menarche (AOR = 1.22, 95% CI: 1.10, 1.37). Childhood physical abuse had a dose-response association with late age at menarche: AOR 1.17 (95% CI: 1.04, 1.32) for mild, 1.20 (95% CI: 1.08, 1.33) for moderate, and 1.50 (95% CI: 1.27, 1.77) for severe physical abuse. Sexual abuse was not associated with late menarche. Childhood abuse was prevalent in this large cohort of U.S. women. Severity of childhood sexual abuse was associated with risk for early onset of menarche, and physical abuse was associated with both early and late onset of menarche.

Abstract 632: Effect of body mass index on the association between smoking and risk of gastric cancer in the Singapore Chinese Health Study

Abstract Background: Tobacco smoking is an established risk factor for gastric cancer. Recently, reports have suggested high body mass index (BMI) as a significant risk factor for esophageal adenocarcinoma whereas the relationship with gastric cancer remains inconsistent. The aim of the current study is to evaluate two potentially modifiable factors, tobacco smoking and increased body mass index, as risk factors for gastric cancer among Singapore Chinese. Methods: We prospectively examined the association between smoking and BMI at baseline, and the risk of developing gastric cancer in the Singapore Chinese Health Study, a cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. Information on body weight, height, cigarette smoking and other lifestyle factors and diet was obtained through in-person interview at enrollment. BMI was calculated using weight in kg divided by height in meter squared (kg/m2). Incidence of cancer and death among cohort participants was obtained via linkage with nationwide registries. Results: As of 31 December 2009, 568 cohort participants who were free of cancer at baseline had developed gastric cancer. Compared to never smokers, current smokers had a 38% increase in risk of gastric cancer (95% confidence interval: 1.12-1.70), with a positive dose-response association between number of cigarettes per day (P for trend=0.002) and number of years of smoking (P for trend=0.005), and gastric cancer risk. After adjustment for cigarette smoking and other potential confounders, hazard ratios (95% confidence interval) of gastric cancer for subjects with BMI 20-&amp;lt;24, 24-&amp;lt;28 and 28+ kg/m2 were 1.30 (1.00-1.68), 1.19 (0.88-1.60), and 1.65 (1.14-2.40), respectively, relative to those with &amp;lt;20 kg/m2 (P for trend=0.063). This dose-response association between increasing BMI and cancer risk was stronger for cardia cancer (P for trend =0.021) than for noncardia cancer (P for trend=0.19). In separate analyses in groups defined by BMI, hazard ratios (95% confidence interval) of gastric cancer for current smokers with BMI of β28, 24-&amp;lt;28, 20-&amp;lt;24, and &amp;lt;20 kg/m2 were 1.11 (0.51-2.45), 1.08 (0.67-1.75), 1.52 (1.16-1.99), and 1.90 (1.05-3.43), respectively, as compared with nonsmokers. The positive dose-response associations between dose and duration of smoking, and gastric cancer risk were limited to lean subjects with BMI&amp;lt;24 kg/m2 and not observed in the more obese subjects. Conclusion: Smokers with relatively low level of BMI had enhanced risk of gastric cancer compared to smokers with higher BMI. Our findings corroborate the hypothesis that lean smokers have increased oxidative DNA damage relative to their non-lean counterparts, which may in turn explain their heightened susceptibility to tobacco carcinogens-induced DNA damage in gastric carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 632. doi:1538-7445.AM2012-632

Urinary Bisphenol A Concentrations and Implantation Failure among Women Undergoing in Vitro Fertilization

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size.Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF).Methods: We used online solid phase extraction–high performance liquid chromatography–isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval.Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06).Conclusion: There was a positive linear dose–response association between BPA urinary concentrations and implantation failure.

Leisure-Time Physical Activity Among Adult and Elderly Individuals in Brazil: A Countrywide Analysis

No data on leisure-time physical activity (LTPA) are available in Brazil for a representative sample of the whole country. The current study describes LTPA levels of the Brazilian adult and elderly populations and explores its association with sex, age, and schooling. A countrywide household-based cross-sectional study was carried out, including separate samples of adult and elderly individuals from 23 states in Brazil selected through a multistage approach. LTPA was assessed using the long version of the International Physical Activity Questionnaire. A cut-off point of 150 minutes per week was used. 12,402 adult and 6617 elderly individuals were interviewed in 100 cities. The proportion of individuals below the 150 minutes per week threshold in terms of LTPA was 82.6% (95% CI 81.9; 83.2) among the adults and 86.5% (95% CI 85.7; 87.3) among elderly individuals. Among adults, prevalence estimates were very consistent across regions. Elderly subjects living in states in the Northeast and North regions of the country were less active than those from the other regions. A clear positive dose-response association was observed between LTPA and schooling. Alarming rates of low levels of LTPA are found in Brazil, thus suggesting the need of urgent actions.

P2-61 Childhood obesity and parental smoking as risk factors for childhood ADHD in Liverpool children

IntroductionADHD prevalence has risen in parallel with rising prevalence of pregnancy smoking and childhood obesity. The objective was to determine the epidemiological association of pregnancy smoking and childhood obesity with...