Population-based Case-control Study Research Articles

Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada

BackgroundIncreasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). MethodsWe conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012–2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). ResultsWe linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944–1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953–1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903–1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833–0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. ConclusionsThis study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Oral contraceptive use in women with spina bifida in Sweden

BackgroundThanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of sexual desires. However, access to reproductive counselling and contraceptive use has been reported to be lower for women with physical and intellectual disabilities compared to the general population. ObjectiveWe investigated oral contraceptive use in women with SB, residing in Sweden and how use varies based on the level of lesion and demographic factors. MethodsThis was a population-based case-control study using annual data from national registers from 2006 to 2015. The sample consisted of 7045 women aged 15–49 years, of which 1173 had a diagnosis of SB. χ2 tests and logistic regression were used to investigate the study objective. ResultsThe rate of oral contraceptive use in women with SB was 24.6 % compared to 34.5 % among the general population. After adjusting for potential confounders women with SB were found to have a lower probability of using oral contraceptives (OR 0.63 95 % CI 0.56–0.71) compared to women without SB. Among women with SB, those with diagnoses Q05.8 (Sacral SB without hydrocephalus) and Q05.9 (SB unspecified) had a higher likelihood of using oral contraceptives compared to other Q05 diagnoses. ConclusionWomen with SB had a lower likelihood of being on oral contraceptives compared to the control group. Further research should investigate if the lower use indicates that oral contraceptives are not an inappropriate method of contraception for women with SB.

Stroke Recurrence Rate and Risk Factors Among Stroke Survivors in Sub-Saharan Africa: A Systematic Review.

Evidence supporting secondary stroke in sub-Saharan Africa is scarce. This study describes the incidence of stroke recurrence and associated risk factors in sub-Saharan Africa. Scientific databases were systematically searched from January 2000 to December 2022 for population-based observational studies, case-control or cohort studies of recurrent stroke involving adults aged 18 years and above in sub-Saharan Africa (SSA). We assessed the quality of the eligible studies using the Critical Appraisal Skills Program (CASP) checklist for observational studies. Six studies met the inclusion criteria and were included in this study.Stroke recurrence rates in SSA ranged from 9.4% to 25%. Majority of the studies were conducted from Western Africa and showed that stroke recurrence rates are high within sub-Saharan Africa ranging from 2% to 25%. The known stroke risk factors such as hypertension, chronic alcohol consumption, etc., remained the leading causes of stroke recurrence. The studies reported a higher mortality rate ranging from 20.5 -23% among those with recurrent strokes compared to primary strokes. This systematic review is an update and summary of the available literature on stroke recurrence within sub-Saharan Africa. Further studies are warranted to assess the outcomes and burden of stroke recurrence in SSA.

Adherence to HEI-2010 and odds of breast cancer according to the menopause status: Evidence from Middle Eastern Country.

Majority of earlier studies have assessed the association between individual healthy eating index-2010 (HEI-2010) and the odds of breast cancer (BC). However, no study has been conducted on the effect of compliance with HEI-2010 and the odds of BC in the Iranian population with a large sample size. Therefore, we aimed to investigate the relationship between the HEI-2010 and the odds of BC in the Iranian population. This population-based case-control study included 350 newly diagnosed cases of BC and 700 healthy controls randomly selected from adult women. HEI-2010 was examined using validated questionnaires. The adherence to HEI-2010 among the participants was divided into four categories. The general characteristics of the participants in the quartiles of the HEI score for categorical variables and continuous variables were evaluated using chi-square and one-way analysis of variance, respectively. Also, using logistic regression analysis, dietary intakes were evaluated in HEI score quartiles. Also, confounding variables were adjusted in different models. People with the highest HEI score had 60% lower odds of BC (OR: 0.40; 95% CI: 0.27, 0.57) than those with the lowest score among post-menopause women. After controlling for age and energy intake, individuals with the highest HEI score were 78% less likely to have BC compared with those with the lowest score (OR: 0.22; 95% CI: 0.14, 0.33). Adjustments for other potential confounders including demographic factors made the association stronger (OR: 0.21; 95% CI: 0.13, 0.32). This association remained significant even after taking BMI into model (OR: 0.27; 95% CI: 0.17, 0.43). Finally, in this study we found an association between HEI-2010 and odds of breast cancer. This association was particularly seen in postmenopausal women. No significant association was found between adherence to HEI-2010 and odds of BC among pre-menopausal.

Abstract 2195: Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study

Abstract Introduction: Ovarian, fallopian tube, and primary peritoneal cancers (hereafter referred to as ovarian cancer) are the most fatal gynecologic cancers. Thus, it is imperative to identify strategies that can reduce the risk of the disease. Several contraceptive methods have been shown to be associated with a reduced risk of ovarian cancer, including combined oral contraceptives, injectable progestins, and tubal ligation. However, the use of these contraceptive methods has been decreasing in the U.S., with a growing preference for intrauterine devices (IUDs) for pregnancy prevention. Previous case-control studies on the association between IUD use and ovarian cancer risk have found inconsistent results. Notably, previous studies had small sample sizes and did not restrict to invasive epithelial tumors. The current analysis assessed the association between IUD use and risk of invasive epithelial ovarian cancer in a large population-based case-control study. Methods: This analysis used data from 1,713 people diagnosed with primary invasive epithelial ovarian cancer (cases) and 2,348 cancer-free people (controls) participating in a case-control study conducted in Los Angeles, CA from 1992-2010. The study consisted of four waves of recruitment with similar enrollment and data collection methods. Logistic regression models were fit to assess the association between IUD use and risk of invasive epithelial ovarian cancer. All models were adjusted for age, race/ethnicity, education, first-degree family history of ovarian cancer, endometriosis, body mass index, duration of combined oral contraceptive use, parity, duration of breastfeeding, tubal ligation, and study wave. Heterogeneity across the study waves and the ovarian cancer histotypes was evaluated using standard meta-analysis techniques. Results: There was no statistically significant association between IUD use and risk of invasive epithelial ovarian cancer (odds ratio=1.09, 95% confidence interval 0.93-1.28). This result was consistent across the study waves and the ovarian cancer histotypes (p-values for heterogeneity>0.05). Conclusion: IUD use was not associated with the risk of invasive epithelial ovarian cancer. Analysis by IUD type (i.e., hormone-releasing vs copper IUDs) was not possible in this study as these data were not collected. Future research should examine whether the type of IUD (i.e. copper versus hormone-releasing) may have different effects on risk of ovarian cancer. Citation Format: Minh Tung Phung, Yuting Wang, Alice W. Lee, Malcolm C. Pike, Anna H. Wu, Celeste Leigh Pearce. Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2195.

Abstract 3441: Application of a maternal comorbidity index to predict childhood cancer risk: A population-based case-control study in Denmark

Abstract Background: Maternal health has been found to be an indicator of children’s health and has also been found to affect the risk of childhood diseases. Children are especially susceptible to in-utero exposures. A mother’s health conditions before and during pregnancy could have important consequences for her child's health, including cancer development, as was observed in some prior studies. Objectives: This study aimed to identify the impact of varying maternal comorbidities on the development of childhood cancers. This study applied an Obstetric Comorbidity Index (Bateman et al, 2013) to examine maternal comorbid conditions in childhood cancer risk. Methods: Using maternal and birth records, and cancer records from the Danish Cancer Registry, we conducted a population-based case-control study with two population groups- the first population included cases (n=2578) and controls (n=64450) with ICD-10 diagnoses from 1994-2013, and the second population included cases (n=8339) and controls (n=208475) with ICD-8 and 10 diagnoses from 1977-2013. Maternal comorbidities were ascertained from the National Patient Register using the Obstetric Comorbidity Index. We estimated the risk of childhood cancer using conditional logistic regression. Results: Multiple gestation pregnancy (OR=1.17, 95% CI 1.05, 1.30), maternal pre-existing diabetes (OR=1.68, 95% CI 1.14, 2.48), congenital heart disease (OR=2.62, 95% CI 1.13, 6.09) and previous cesarean delivery (OR=1.35, 95% CI 1.03, 1.75) showed an increased risk of childhood cancers (all types combined). Children born to mothers between the ages of 35 and 39 also had a higher risk of cancer as compared to those born before. In the 1977-2013 population, there was an increased risk of acute lymphocytic leukemia (ALL; OR=1.08, 95% CI 1.04, 1.13) and rhabdomyosarcoma (OR=1.13, 95% CI 1.01, 1.27) for each unit of increase on the Obstetric Comorbidity Index. There was also an increased risk of retinoblastoma (OR=1.16, 95% CI 1.01, 1.32) for each unit of increase on the maternal comorbidities index in the 1994-2013 population. Examining mothers that had a score of one or more in the Obstetric Comorbidity Index, there was a higher risk of ALL (OR=1.43, 95% CI 1.26, 1.62), non-Hodgkin lymphoma (OR=1.50, 95% CI 1.17, 1.91), Burkitt lymphoma (OR=1.71, 95% CI 1.12, 2.61), and rhabdomyosarcoma (OR=1.58, 95% CI 1.10, 2.26) for children whose mothers with at least one maternal comorbidity. A similar trend was observed in the 1994-2013 population for ALL, non-Hodgkin lymphoma, and Burkitt lymphoma. Conclusion: The results of the study show varying effects of exposure to one or more maternal comorbidities on individual pediatric cancer types, and an overall increased risk of most cancers development in children with exposure of mothers to 1 or more maternal comorbidities. Citation Format: Tobiloba Adanma Adenekan, Julia E. Heck, Cheng Yin, Johnni Hansen. Application of a maternal comorbidity index to predict childhood cancer risk: A population-based case-control study in Denmark [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3441.

Abstract 2209: Tattooing and risk of melanoma: A population-based case-control study in Utah

Abstract Background: Carcinogens have been observed in many tattoo inks which can form new carcinogenic compounds when exposed to ultraviolet radiation and can accumulate in the lymph nodes and other organs. Tattooing can result in short- and long-term inflammatory and immune responses. At least 38 cases of melanoma have been reported in tattoos. The incidence of melanoma in Utah is the highest in the U.S., and potentially modifiable risk factors are of public health interest. In this study, we evaluated associations between tattooing and melanoma risk. Methods: We utilized a population-based case-control study of 514 incident in situ (284 men and 230 women) and 534 invasive (285 men and 249 women) melanoma cases diagnosed in Utah between 2020-2021. Controls (n=5,240) were selected from respondents to the Utah Behavioral Risk Factor Surveillance System (BRFSS) survey and frequency matched to cases in a 5:1 ratio on sex, age, race, and ethnicity. We fit logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating ever tattooing with in situ and invasive melanoma risk, adjusting for age, education level, race, and ethnicity, separately for women and men. We then fit logistic models stratified by education level (< four-year college degree/four-year college degree or more) and models stratified by age (< 50 years/50+ years), separately for women and men. Results: Among men, the prevalence of tattooing was 7% for both in situ and invasive cases, and 11% for controls. Among women, tattooing prevalence was 20% for in situ cases, 15% for invasive cases, and 18% for controls. Ever tattooing was associated with decreased invasive melanoma risk among men (OR=0.62 [95% CI: 0.37-1.02]), particularly among those who had less than a four-year college degree (0.52 [0.28-0.99]), and among ages 50+ (0.36 [0.16-0.84]). Among men, the OR for ever tattooing and in situ melanoma was in the same direction as invasive melanoma, but the estimate was statistically imprecise (0.73 [0.45-1.19]). Among women, we did not observe an association between ever tattooing and invasive melanoma (0.83 [0.56-1.20]), while the association between ever tattooing and in situ melanoma was statistically imprecise (1.25 [0.87-1.80]). However, ever tattooing was associated with a nearly two-fold increased risk of in situ melanoma among women with a four-year college degree (1.98 [1.21-3.26]), but not for those without a college degree (0.89 [0.52-1.50]). Conclusion: These findings do not suggest that there is an association between tattooing and melanoma. Associations between tattooing and health-seeking behaviors, which may vary by sex and other demographic factors, may influence associations with melanoma diagnosis, particularly for in situ melanoma. This study is the first step in investigating whether reported cases of melanoma arising in tattoos are coincidental or whether tattoos may be associated with an increased risk of melanoma. Citation Format: Rachel D. McCarty, Britton Trabert, Morgan M. Millar, David Kriebel, Laurie Grieshober, Mollie E. Barnard, Lindsay J. Collin, Katherine A. Lawson-Michod, Jeffrey A. Gilreath, Douglas Grossman, John Hyngstrom, Paul J. Shami, Jennifer A. Doherty. Tattooing and risk of melanoma: A population-based case-control study in Utah [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2209.

Abstract 6088: Predicting the risk of any-type cancer in asymptomatic adults using noninvasive glycosaminoglycan profiling

Abstract Background: Early detection of cancers through screening can reduce mortality. However, screening excludes individuals not considered at an increased risk of developing cancer, as determined by age, sex, or tobacco use. No molecular biomarker is routinely used to predict risk. Here, we investigated urine glycosaminoglycan profiles (GAGomes) as noninvasive biomarkers for any-cancer risk prediction. Methods: In this population-based case-control study, we included adults aged over 18 years from the Lifelines Cohort Study, Netherlands who were presumed healthy at baseline. All cases who self-reported any-type cancer or died by the 5-year study visit were confirmed in the Dutch Cancer Registry and matched 1:3 to randomly selected controls (1:1 for the interim analysis). We first developed a logistic regression reference model, including age, sex, and clinical variables to predict any-type cancer. Next, we added urine GAGomes (as a single aggregate score) to the model and assessed model improvement using the likelihood ratio test. We categorized the output of the saturated model (clinical variables plus urine GAGome score) into four groups based on bespoke specificity cut-offs: low-, moderate-, intermediate-, and high-risk. We estimated odds-ratios (ORs) for their association with any-type cancer compared to the moderate-risk group, as well as their sensitivity across subsets. Using the so-estimated OR in the high-risk group, we calculated the minimum pre-test 5-year absolute risk needed to reclassify an adult into a post-test 5-year absolute risk >3.00%. Results: In the interim analysis, we included 2054 adults (median age = 51 years, 57% females). Of them, 924 were diagnosed with any-type cancer over a 6 year-follow-up period (median time to diagnosis = 1.4 years). Urine GAGomes were found to be independent risk factors when added to the reference model, explaining 27% of the variance (Nagelkerke R2 = 0.26 vs. 0.21, p < 0.0001). The ORs in the low-, intermediate-, and high-risk groups were 0.05 (95% CI: 0.02-0.13 p < 0.0001), 5.31 (95% CI: 3.84-7.48, p < 0.0001) and 27.6 (95% CI: 14.3 - 51.6, p < 0.0001), respectively. The high-risk group detected +80% more cancers than the reference model at the same specificity (99.29%), particularly in situ and stage I (+204% and +64%) and among those aged 50-69 (+247%). Adults with a pre-test 5-year absolute risk > 0.25% returning a high-risk group would be reclassified to a post-test 5-year absolute risk > 3.00% for any-type cancer. Conclusion: Implementing urine GAGomes as a strategy for risk-stratified targeted screening could identify adults with increased risk of any-type cancer who are currently excluded from screening. Citation Format: Francesco Gatto. Predicting the risk of any-type cancer in asymptomatic adults using noninvasive glycosaminoglycan profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6088.

Abstract 839: Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer

Abstract Introduction: Recent studies have reported an increased bladder cancer risk with occupational exposure to organic solvents, including exposure to benzene, toluene, and xylene (BTX). The metabolism of solvents is known to be influenced by genetic susceptibility. Here, we evaluated the association between BTX and bladder cancer, stratified by genotype in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of solvents. Methods: We evaluated if single-nucleotide polymorphisms (SNPs) modified the association between BTX exposure and bladder cancer risk in 1182 cases and 1408 controls from a population-based case-control study in New England. Ever and cumulative lifetime exposure to BTX was assessed using occupational histories obtained by personal interviews and exposure-oriented modules in conjunction with a job-exposure matrix. Genotyping was conducted using Illumina arrays and GSTM1 and GSTT1 deletion were determined using melt curve/copy number assays. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between BTX exposure and bladder cancer, stratified by genotype and to calculate p-values for multiplicative interaction. Results: Ever exposure to BTX was more strongly associated with bladder cancer risk among individuals with the GSTT1 null (deletion) genotype (OR 3.53, 95% CI 1.26-9.89), while exposed individuals with the GSTT1 active genotype had a diminished risk (OR 1.40, 95% CI 0.93-2.10, P-interaction = 0.06). The association between benzene exposure and bladder cancer was similarly modified by GSTT1 genotype (carriers of the deletion: OR 5.19, 95% CI 1.91, 14.13; carriers of one or two copies: OR 1.22, 95% CI 0.79, 1.89, p-interaction=0.008). Conclusion: GSTT1 genotype has been shown to impair the metabolism of solvents, particularly for benzene. Here we show that bladder cancer risk is higher among those exposed to solvents who also harbor a common deletion in GSTT1, adding to the evidence of a plausible link between BTX exposures and bladder cancer risk. Citation Format: Deborah Tadesse, Nathaniel Rothman, Shuai Xie, Lauren Hurwitz, Melissa C. Friesen, Dalsu Baris, Molly Schwenn, Alison Johnson, Margaret Karagas, Debra T. Silverman, Stella Koutros. Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 839.

Abstract 2217: Associations between intrauterine device use and ovarian cancer risk among 11 population-based case-control studies

Abstract Background: Intrauterine device (IUD) use has increased while oral contraceptive (OC) use has decreased among premenopausal women. It is unknown whether IUDs offer protection against epithelial ovarian cancer (EOC), similar to OCs, or may increase risk. Therefore, we examined the association between IUD use and EOC risk. Methods: Information on contraception use was obtained through questionnaires from 11 studies participating in the Ovarian Cancer Association Consortium and African-American Cancer Epidemiology Study. Study-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional multivariable logistic regression, and heterogeneity between studies was assessed using Cochran Q and I2 statistics. There was no evidence of heterogeneity, thus data were pooled. We assessed potential effect modification by decade of birth, race, parity, and personal history of endometriosis by reporting stratum-specific estimates and tested for multiplicative interaction by comparing models with and without interaction terms via likelihood ratio test. Polytomous logistic regression was used to estimate histotype-specific associations. Results: Results were pooled for 11,033 EOC cases and 13,358 controls. There were 2,656 (19.9%) IUD users (mostly non-hormonal) and 8,923 (66.8%) OC users among controls compared to 1,933 (17.5%) IUD users and 6,318 (57.3%) OC users among cases. IUD use was associated with lower risk of endometrioid (OR: 0.73, 95% CI: 0.62-0.86) and clear cell (OR: 0.63, 95% CI: 0.48-0.80), but not high-grade serous subtypes (OR: 1.05, 95% CI: 0.98-1.14), with significant heterogeneity by histotype (p=0.0006). Among studies that collected data on IUD type, we observed a non-significant inverse association between hormonal IUD use and EOC (OR: 0.72, 95% CI: 0.51-1.03); however, only 51 cases reported hormonal IUD use. Among those who used both IUD and OCs, there was no association with the order of contraception use and EOC. There were no major differences in the associations of age at first use, duration of use, or time since last use and EOC risk. Among parous women, IUD use before first pregnancy was associated with a non-significant reduced odds of EOC (OR: 0.82, 95% CI: 0.65-1.04). We also observed a statistically significant interaction between IUD use and endometriosis with reduced odds of EOC associated with IUD use among women with endometriosis (OR: 0.77, 95% CI: 0.60-0.98) but not those without endometriosis (OR: 0.96, 95% CI: 0.90-1.03, p-interaction=0.05). Discussion: IUD use was associated with lower clear cell and endometrioid EOC risk and may be most protective among women with endometriosis. Future research should include cohorts of women with a higher prevalence of hormonal IUD use to determine the impact of changing contraceptive trends on ovarian cancer burden and identifying preventive strategies for women at high risk. Citation Format: Jennifer M. Mongiovi, Ana Babic, Naoko Sasamoto, Lauren Peres, Holly Harris, Mollie E. Barnard, Shelley S. Tworoger, Anita Koushik, Joellen M. Schildkraut, Jennifer A. Doherty, Kathryn L. Terry, the Ovarian Cancer Association Consortium & the African-American Cancer Epidemiology Study. Associations between intrauterine device use and ovarian cancer risk among 11 population-based case-control studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2217.

Maternal risk factors for congenital vertebral formation and mixed defects: A population-based case-control study.

The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different subgroups of vertebral anomalies. Therefore, we assessed and identified potential maternal risk factors for these anomalies and hypothesized that diabetes, other chronic diseases, smoking, obesity, and medication in early pregnancy would increase the risk of congenital vertebral anomalies. All cases with congenital vertebral anomalies were identified in the Finnish Register of Congenital Malformations from 1997 to 2016 for this nationwide register-based case-control study. Five matched controls without vertebral malformations were randomly selected. Analyzed maternal risk factors included maternal age, body mass index, parity, smoking, history of miscarriages, chronic diseases, and prescription drug purchases in early pregnancy. The register search identified 256 cases with congenital vertebral malformations. After excluding 66 syndromic cases, 190 non-syndromic malformations (74 formation defects, 4 segmentation defects, and 112 mixed anomalies) were included in the study. Maternal smoking was a significant risk factor for formation defects (adjusted odds ratio 2.33, 95% confidence interval 1.21-4.47). Also, pregestational diabetes (adjusted odds ratio 8.53, 95% confidence interval 2.33-31.20) and rheumatoid arthritis (adjusted odds ratio 13.19, 95% confidence interval 1.31-132.95) were associated with mixed vertebral anomalies. Maternal pregestational diabetes and rheumatoid arthritis were associated with an increased risk of mixed vertebral anomalies. Maternal smoking increases the risk of formation defects and represents an avoidable risk factor for congenital scoliosis. III.

Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

Association between sun exposure habits and disease progression in multiple sclerosis.

Higher latitude has been associated with increased occurrence of multiple sclerosis (MS) and with more severe disease. The aim was to study the impact of sun exposure habits on MS disease progression and health-related quality of life. Patients from a population-based case-control study were categorized based on sun exposure habits at diagnosis and were followed up to 15 years post-diagnosis through the Swedish MS registry (n = 3314) with regard to changes in Expanded Disability Status Scale (EDSS). Linear mixed models were used to analyse long-term changes, while Cox regression models, with 95% confidence intervals, were used to investigate outcomes, including 24-week confirmed diasability worsening, EDSS3, EDSS4, and physical worsening as measured by the physical component of the Multiple Sclerosis Impact Scale 29. Compared to average sun exposure (median value), low exposure to sunlight was associated with faster EDSS progression, increased risk of confirmed disability worsening (hazard ratio [HR] 1.48, 95% CI 1.21-1.81), increased risk of reaching EDSS 3 (HR 1.35, 95% CI 1.02-1.79), EDSS 4 (HR 1.47, 95% CI 1.01-2.20) and self-reported physical worsening (HR 1.27, 95% CI 1.00-1.62). Significant trends revealed a lower risk of unfavourable outcomes with increasing sun exposure. Very low levels of sun exposure are associated with worse disease progression and health-related quality of life in patients with MS.

XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis.

Endometrial carcinoma's (EC) etiology is complex and involves DNA repair gene polymorphisms like XRCC1-Arg399Gln and hOGG1-Ser326Cys, but their association with the disease is unclear. Following PRISMA, we conducted a systematic review and meta-analysis, collecting data from four databases. The studies needed to be population-based case-control studies examining the association between the named polymorphisms and EC. Quality was assessed with the Newcastle-Ottawa Scale. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated, and subgroup analyses were conducted based on ethnicity. Seven studies were included. Both polymorphisms were found to significantly increase EC risk, particularly in Caucasians. XRCC1-Arg399Gln showed a dominant model OR of 1.14 (95% CI: 1.01-1.29) and a homozygous model OR of 1.59 (95% CI: 1.12-2.25). The heterozygote model OR for hOGG1-Ser326Cys was 1.29 (95% CI: 1.02-1.63), and the allele OR was 1.31 (95% CI: 1.07-1.60). XRCC1-Arg399Gln and hOGG1-Ser326Cys may increase EC risk, primarily in Caucasian women, emphasizing the role of DNA repair in disease susceptibility. More extensive studies are needed to validate these findings in diverse ethnicities and investigate other DNA repair gene polymorphisms.

Increasing Risk of Dementia Among Patients with Subsequent Epilepsy Within 2 Years Post-Traumatic Brain Injury: A Population-Based Case-Control Study.

Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial. This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period. This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression. Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a >3.03 times risk of dementia after correcting for age, sex, and comorbidities. These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.

A search for factors associated with reduced carbohydrate intake and NTD risk in two population-based studies.

Two population-based case-control studies have reported an increased risk of neural tube defect (NTD)-affected pregnancies among women with low carbohydrate diet in the periconceptional period. Given that only two studies have investigated this association, it is unclear to what degree the findings could be impacted by residual confounding. Here, we further interrogated both studies that observed this association with the objective to identify factors from a much larger number of factors that might explain the association. By employing a machine learning algorithm (random forest), we investigated a baseline set of over 200 variables. These analyses produced the top 10 variables in each data set for cases and controls that predicted periconceptional low carbohydrate intake. Examining those prediction variables with logistic regression modeling, we did not observe any particular variable that substantially contributed to the NTD-low carbohydrate association in either data set. If there are underlying factors that explain the association, our findings suggest that none of the 200+ variables we examined were sufficiently correlated with what that true explanatory exposure may be. Alternatively, our findings may suggest that there are other unidentified factor(s) at play, or the association observed in two independent data sets is directly related to low carbohydrate intake.

Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis.

A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow-up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31-52) were considered PwUD. They completed a modified questionnaire, previously used in a population-based case-control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS-like symptoms. Compared to controls (n=548) and PwMS (n=277), fewer PwUD were currently smoking (p=.4 and p=.03), consumed less alcohol (p=.04 and p=.01), and had children (p=.02 and p=.002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p<.001 and p<.001). UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.

Association between sinusitis and incident rheumatic diseases: a population-based study

ObjectivesTo determine whether antecedent sinusitis is associated with incident rheumatic disease.MethodsThis population-based case–control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three...

Linkage and association of rs3110045 and rs28499085 variants in the thyrotropin-releasing hormone receptor (TRHR) gene with the risk of familial type 2 diabetes

Type 2 diabetes (T2D) is a chronic and prevalent multisystemic disease that significantly increases morbidity and mortality. Dysfunction of the thyroid hormone system is common in patients with T2D, increasing their risk of both hyperthyroidism and hypothyroidism. Several components of the thyroid system are candidate risk genes for T2D. The thyrotropin-releasing hormone receptor (TRHR) gene encoding for TRHR is of particular interest since it is expressed by the dorsomedial hypothalamus neurons, which are known to regulate food intake. In humans, a variant in the TRHR gene has been previously reported in T2D patients in a population-based case-control study but not in familial T2D. We recruited 212 multigenerational families with T2D originated from the Italian peninsula with multiple cases of T2D and tested, via Pseudomarker 9 single nucleotide polymorphisms (SNPs) in the TRHR gene for linkage and linkage disequilibrium (i.e., linkage plus association) to/with T2D. We identified 2 novel risk variants (rs3110045 and rs28499085) significantly linked to and associated with the risk of T2D in the Italian families across several inheritance models. Our study is the first to confirm the previously reported association of TRHR gene with T2D and extends the risk to familial inheritance. However, functional and replication studies are still needed to confirm these results.