Evidence Of Statistical Interaction Research Articles

Abstract PR-009: Associations between PM2.5, vegetation density and childhood brain tumors: a case-control registry-based study from Texas 1995-2011

Abstract Background: Air pollution has been reported to be associated with some childhood cancers, namely leukemias. Less is known about air pollution and childhood brain tumor risk. In adult cancers, increasing vegetation density, or greenness, has been inversely associated with cancer incidence and survival. The interplay between air pollution and greenness, which co-occur, in childhood cancer etiology is unclear. Therefore, we sought to estimate the association between prenatal and early life exposure to air pollution, greenness, and childhood cancer in Texas (1995-2011). Materials and Methods: We included 1,316 individuals with a childhood brain tumor diagnosed <17 years of age and 109,762 age- and sex-matched controls. We linked birth certificate residential address to census tract annual average particulate matter 2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI) to approximate prenatal and early life exposure to greenness and air pollution. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between PM2.5 and NDVI interquartile range (IQR) increases and brain tumors. Models were adjusted for birth year, sex, maternal race/ethnicity, and area-level socioeconomic status (Yost index). Results: The following brain tumor types were included: ependymoma (n=136), astrocytoma (n=619), medulloblastoma (n=187), PNET (n=57), ATRT (n=54), and other gliomas (n=263). Average birth year PM2.5 and NDVI exposure levels were similar in cases and controls, 11 µg/m³ and 0.4, respectively. Each IQR increase (2.6 µg/m³) in PM2.5 was associated with ependymoma (OR: 1.27, 95% CI: 1.01-1.60) when adjusting for control-derived quartiles of NDVI. Conversely, after adjusting for PM2.5 quartiles, each IQR increase in NDVI (0.13) was inversely associated with ependymoma in those diagnosed at 0-4 years of age (OR: 0.75, 95% CI: 0.56-0.97) and with medulloblastoma in those aged 0-16 years at diagnosis (OR: 0.75, 95% CI: 0.62-0.91). There was no evidence of statistical interaction between NDVI and PM2.5 (all Likelihood Ratio Test p-values>0.05) for any brain tumors. Conclusions: Increasing residential air pollution during prenatal and early life increased the risk of childhood ependymoma in Texas independent of greenness. Conversely, increasing greenness exposure in prenatal and early life decreased the risk of ependymoma and medulloblastoma independent of PM2.5. These findings highlight the complex relationship between air pollution and greenness in childhood cancer etiology. Citation Format: Lindsay Williams, David Haynes, Jeannette Sample, Laura McGuinn, Thanh Hoang, Philip Lupo, Michael Scheurer. Associations between PM2.5, vegetation density and childhood brain tumors: a case-control registry-based study from Texas 1995-2011 [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr PR-009.

PM2.5, vegetation density, and childhood cancer: a case-control registry-based study from Texas 1995-2011.

Air pollution is positively associated with some childhood cancers while greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early life air pollution and greenness exposure and childhood cancer in Texas (1995-2011). We included 6,101 cancer cases and 109,762 controls (aged 0-16 years). We linked residential birth address to census tract annual average particulate matter ≤2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (OR) and 95% confidence intervals (95% CI) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests). Increasing residential early life PM2.5 exposure was associated with all childhood cancers (OR 1.10, 95% CI: 1.06-1.15), lymphoid leukemias (OR: 1.15, 95% CI: 1.07-1.23), Hodgkin lymphomas (OR: 1.27, 95% CI: 1.02-1.58), non-Hodgkin lymphomas (OR: 1.24, 95% CI: 1.02-1.51), ependymoma (OR: 1.27, 95% CI: 1.01-1.60) and others. Increasing NDVI exposure was inversely associated with ependymoma (0-4-year-old OR: 0.75, 95% CI: 0.58-0.97) and medulloblastoma (OR: 0.75, 95% CI: 0.62-0.91), but positively associated with malignant melanoma (OR: 1.75, 95% CI: 1.23-2.47) and Langerhans cell histiocytosis (OR: 1.56, 95% CI: 1.07-2.28). There was evidence of statistical interaction between NDVI and PM2.5 (p < .04) for all cancers. Increasing early life exposure to PM2.5 increased the risk of childhood cancers. NDVI decreased risk of two cancers yet increased risk of others. These findings highlight the complexity between PM2.5 and NDVI in cancer etiology.

Lifetime alcohol consumption patterns and young-onset breast cancer by subtype among Non-Hispanic Black and White women in the Young Women's Health History Study.

The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50years of age. Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative). Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed. Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case–control study in an English population-based cohort

BackgroundMultiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups.AimTo determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds.MethodsWe conducted a nested case–control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity.ResultsWe included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis—smoking, obesity, infectious mononucleosis, low vitamin D, and head injury—were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses.Conclusions and relevanceEstablished modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality

Background and aimsElevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality. MethodsThe Copenhagen General Population Study randomly recruited white Danish individuals aged 20–100 years in 2003–2015 and followed them for a median 9.5 years. ASCVD was cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization. ResultsIn 103,221 individuals, we observed 2,454 (2.4%) myocardial infarctions, 5,437 (5.3%) ASCVD events, and 10,521 (10.2%) deaths. The hazard ratios increased with each of stepwise higher remnant cholesterol and stepwise higher C-reactive protein. In individuals with the highest tertile of both remnant cholesterol and C-reactive protein compared to individuals with the lowest tertile of both, the multivariable adjusted hazard ratios were 2.2 (95%CI:1.9–2.7) for myocardial infarction, 1.9 (1.7–2.2) for ASCVD, and 1.4 (1.3–1.5) for all-cause mortality. Corresponding values for only the highest tertile of remnant cholesterol were 1.6 (1.5–1.8), 1.4 (1.3–1.5), and 1.1 (1.0–1.1), and those for only the highest tertile of C-reactive protein were 1.7 (1.5–1.8), 1.6 (1.5–1.7), and 1.3 (1.3–1.4), respectively. There was no statistical evidence for interaction between elevated remnant cholesterol and elevated C-reactive protein on risk of myocardial infarction (p = 0.10), ASCVD (p = 0.40), or all-cause mortality (p = 0.74). ConclusionsDual elevated remnant cholesterol and C-reactive protein confers the highest risk of myocardial infarction, ASCVD, and all-cause mortality, that is, compared to either of these two factors individually.

Association Between Healthy Dietary Patterns and Markers of Oxidative Stress

ObjectivesOxidative stress is involved in chronic disease etiology and the aging process and is related to antioxidant intake. However, less is known about the relationship between dietary patterns and markers of oxidative stress. We assessed cross-sectionally the association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary F2-isoprostanes (8-iso-PGF2α and 8-iso-PGF2α-M), which are established biomarkers of oxidative stress. MethodsData were obtained from 844 premenopausal and 454 postmenopausal women participating in the Sister Study who had urinary samples analyzed for F2-isoprostanes. Responses from a 110-item validated food frequency questionnaire (FFQ) at baseline were used to calculate dietary pattern scores. Concentrations of 8-iso-PGF2α and its metabolite (8-iso-PGF2α-M) were measured by GC/MS for samples from premenopausal women and LC/MS for samples from postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes among pre-menopausal and post-menopausal women separately. ResultsAmong premenopausal women, we observed significant inverse associations between the four dietary indices and mean 8-iso-PGF2α (aMED βQ4vsQ1: –0.15, 95% CI: –0.25, –0.05; DASH βQ4vsQ1: –0.15, 95% CI: –0.25, –0.25; aHEI βQ4vsQ1: –0.15, 95% CI: –0.25, –0.05; HEI-2015 βQ4vsQ1: –0.17, 95% CI: –0.27, –0.07). These associations were modified by age, education, income, and BMI, though there was no evidence of statistical interaction. In a sensitivity analysis, estimates did not substantially differ by the presence or absence of chronic disease. Among postmenopausal women, aHEI was associated with mean 8-iso-PGF2α and 8-iso-PGF2α-M (β8-iso-PGF2α: –0.003, 95% CI: –0.01, –0.005, β8-iso-PGF2α-M: –0.003, 95% CI: –0.01, –0.005). No other significant findings were observed among postmenopausal women. ConclusionsHealthy dietary patterns may be associated with reduced oxidative stress, particularly among premenopausal women. Funding SourcesNational Institute of Environmental Health Sciences, NIH Office of Dietary Supplements, Avon Foundation, T32 from NIH-NIGMS.

Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study.

There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37-39weeks OR: 0.84, 95% CI 0.73-0.97) and ependymoma (female, 40 vs. 37-39 OR: 1.78, 95% CI 1.14-2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29-3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01-1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03-2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59-0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21-4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26-2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12-0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25-29 OR: 2.17, 95% CI 1.13-4.19; ≥ 35 vs. 25-29 OR: 2.44, 95% CI 1.28-4.64). These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.

Abstract 785: Is genetic ancestry associated with mortality risk after accounting for neighborhood socioeconomic status? A study of African American men

Abstract Background Genetic ancestry, a correlate of self-identified race/ethnicity, could be associated with mortality risk, allowing for more targeted treatments for cancer and other chronic diseases. However, associations may be confounded by neighborhood socioeconomic status (nSES). We investigated whether African ancestry and nSES were independently associated with all-cause mortality in a cohort of African American trial participants. Methods We constructed a cohort of American-born participants of African descent from the Prostate, Lung, Colorectal and Ovarian screening trial. Participants were enrolled from 1993-1998 and followed through 2019 or until death, whichever came first. Genetic ancestry (% African) was estimated using a principal components analysis of genome-wide SNP data and validated against European, African, and Asian panels. A nSES index was estimated using principal component analysis of census tract measures of income, housing, and employment. Census tract was assessed in 2012 for residences of living participants. Last known address was assigned to participants who died prior to 2012. We assigned 2000 census data to those who died prior to 2010, and assigned 2006-2010 American Community Survey data to those who were alive after 2010. Hazard ratios for associations between these variables and all-cause mortality were estimated using sequentially adjusted Cox proportional hazards models with sociodemographic, behavioral, and neighborhood contextual covariates. We tested whether mortality associations with ancestry varied by nSES using multiplicative interaction terms. All tests were two-sided with alpha=0.05. Results Among 2239 African American participants, there were 901 deaths over 40,767 person-years of follow-up. Mean baseline age was 61.7, 45% were men, and the mean percentage of African ancestry was 74.3. In unadjusted models, a 10% increase in African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12), but this attenuated to the null after adjusting for covariates (aHR: 1.01, 95% CI: 0.96, 1.06). Participants in nSES Q5 had 45% lower rate of mortality compared to those in Q1 in unadjusted models (HR: 0.55, 95% CI: 0.44, 0.68, Ptrend&amp;lt;.0001); similarly, this was attenuated after adjusting for covariates (aHR: 0.74, 95% CI: 0.57, 0.98, Ptrend=0.017). There was no evidence of statistical interaction between ancestry and nSES. Discussion Our findings suggest that nSES is a stronger independent correlate of mortality than genetic ancestry, which was only weakly associated with mortality after accounting for other factors. Larger studies with wider variability in African ancestry and geographic context are needed to confirm these findings. Citation Format: Hari S. Iyer, Scarlett L. Gomez, Iona Cheng, Timothy R. Rebbeck. Is genetic ancestry associated with mortality risk after accounting for neighborhood socioeconomic status? A study of African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 785.

Increased Serum Glucose is not a Covid-19 Mortality Predictor in Elderly Patients

COVID-19 is causing a current pandemic with high mortality, in which older age is an important risk factor. Few studies have examined whether risk factors for death by COVID-19 are similar in elderly and younger patients. We reviewed electronic hospital records of all consecutive adult patients admitted and analyzed reported COVID-19 mortality risk factors stratified by age group (under 60 vs. 60 and over). In univariate analyses admission date, sex, age, oxygen saturation, hyperglycemia (defined as admission glucose>180mg/dl) and lactate dehydrogenase were associated with COVID-19 mortality in younger patients, while only sex, oxygen saturation and lactate dehydrogenase were associated with mortality in the elderly. Mortality for younger subjects without hyperglycemia was 39.1%, while it was 66.7% in for younger subjects with hyperglycemia, similar to the mortality in the 60 and over age group (66.7% non-hyperglycemic, 60.3% hyperglycemic). This pattern was also observed in multivariate logistic regression with COVID-19 mortality as outcome, where after adjusting for admission date, sex, age, oxygen saturation, lactic dehydrogenase and D-dimer the OR for hyperglycemia was 2.34 (95% CI 1.11-5.03) in the younger age group, while in the elderly the OR was 0.50 (95% CI 0.17-1.37), with evidence of statistical interaction (p = 0.025). This behavior could be explained by an acute effect of SARS-CoV-2 on pancreatic tissue that affects mainly younger subjects. In conclusion, hyperglycemia is not associated with increased mortality in subjects aged over 60.

PDB62 INTERACTION OF HOUSEHOLD AND NEIGHBORHOOD SOCIOECONOMIC STATUS IN THE CHILDHOOD OBESITY EPIDEMIC IN THE UNITED STATES

To determine if the association between neighborhood socioeconomic status (SES) and childhood overweight or obesity varies across household SES levels. Second, determine if having higher household or neighborhood SES mitigates any negative effect of having lower levels in the other SES dimension. We used the first-grade round of 2012 Early Childhood Longitudinal Study (ECLS-K). Household SES was defined based on income, education and occupation. Neighborhood SES was defined by the percent of households living in poverty in the child’s school district. Utilizing sampling weights and accounting for sample design, log-binomial regression models were fitted to estimate the association between neighborhood SES and obesity prevalence and to test whether this association varied by household SES. Predicted probabilities of overweight/obesity were estimated for each combination of household and neighborhood SES. In adjusted models, low neighborhood SES was associated with increased prevalence of overweight/obesity (RR:1.84, 95%CI 1.48, 2.29). This association varied significantly by household SES (p-value of the interaction = 0.002). The multiplicative interaction indicated that having low neighborhood SES was associated with increased probability of overweight/obesity among children from high SES-households (Prevalence Ratio (PR)neighborhood SES:1.87, 95%CI 1.51,2.30) but having low neighborhood SES did was not associated with additionally increased probability of obesity for children from low SES-household (PRneighborhood SES:1.10, 95%CI 0.92,1.32). Children with either low SES-households or low neighborhood SES had the highest predicted probabilities of overweight/obesity, but the effects were not multiplicative. There is statistical evidence of interaction between the two dimensions of SES. However, lower SES in either of them is enough to place children at high risk of overweight or obesity. Higher levels in one dimension do not mitigate the association between low resources on the other dimension and childhood overweight/obesity.

Everyday Racial Discrimination and Hypertension among Midlife African American Women: Disentangling the Role of Active Coping Dispositions versus Active Coping Behaviors.

Racial discrimination, a psychosocial stressor, may contribute to disproportionate rates of hypertension among African American women. Coping moderates the effects of psychosocial stress on health. Coping dispositions describe stable personality characteristics, whereas contextual frameworks emphasize flexible coping behaviors in response to specific stressful encounters. Using data from the African American Women’s Heart and Health Study—a non-probability cross-section of 208 midlife African American women in Northern California—we estimated the association between everyday racial discrimination (Everyday Discrimination Scale, EDS) and prevalence of hypertension (HTN), and evaluated moderation by coping disposition (John Henryism Active Coping scale, JH) versus context-specific active coping behavior (Active Coping with Racism scale, ACR). There were no main associations between EDS, JH, or ACR on HTN prevalence. There was evidence of statistical interaction between EDS and ACR (p-int = 0.05), but not JH (p-int = 0.90). Among those with high levels of ACR, reporting monthly (prevalence ratio (PR) = 2.35, 95% confidence interval (CI) = 1.13, 4.87), weekly (PR = 2.15, 95% CI = 1.01, 4.61), or daily (PR = 2.36, 95% CI = 1.14, 4.88) EDS was associated with higher HTN prevalence, versus reporting racial discrimination yearly or less. In contrast, among those with low levels of ACR, reporting more chronic racial discrimination was associated with lower hypertension prevalence, although results were less precise. Findings suggest that ongoing active coping with chronic racial discrimination may contribute to hypertension risk among African American women.

Genetic variants in CYP and GST genes, smoking and risk for head and neck cancers: a gene-environment interaction hospital-based case-control study among Canadian Caucasians.

The evidence for genetic polymorphisms in genes encoding Cytochrome P450 (CYP) and Glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms (SNPs) and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada. The study involved 389 incident SCCHN cases and 429 controls, frequency-matched by age and sex, recruited from four main hospitals between 2005 and 2013. Life-course based interviews collected information on tobacco smoking history and other risk behaviors. DNA was isolated from oral exfoliated cells and genotyped for genetic variants. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for main, joint effect, stratum-specific and interaction estimates among non, moderate, and heavy smokers. Carriers of GSTP1 105Val (vs. non-carriers) had a lower risk of SCCHN (OR=0.71, 95% CI: 0.53, 0.95), which was observed for heavy smokers (OR=0.59, 95% CI: 0.36, 0.95) and non-smokers alike (OR= 0.49, 95% CI: 0.24, 0.98). The decreased risk associations were also conserved among HPV negative individuals. There was no evidence for statistical interaction with smoking on additive or multiplicative scales for any of the variants analysed. Of CYP and GST polymorphisms detected in Canadian Caucasians, only GSTP1 105Val was associated with a decreased risk for SCCHN.

New-generation drug-eluting stents for left main coronary artery disease according to the EXCEL trial enrollment criteria: Insights from the all-comers, international, multicenter DELTA-2 registry

BackgroundPercutaneous coronary intervention (PCI) has been established as an alternative treatment option to coronary artery by-pass graft (CABG) surgery in patients with left main coronary artery disease (LMCAD). Whether the findings of randomized controlled trials are applicable to a real-world patient population is unclear. MethodsWe compared the outcomes of PCI with new-generation DES in the all-comer, international, multicenter DELTA-2 registry retrospectively evaluating mid-term clinical outcomes with the historical CABG cohort enrolled in the DELTA-1 registry according to the EXCEL key inclusion or exclusion criteria. The primary endpoint was the composite of death, myocardial infarction, or stroke at the median time of follow-up time of 501 days. The consistency of the effect of DELTA-2 PCI versus DELTA-1 CABG according to the EXCEL enrollment criteria was tested using propensity score-adjusted Cox regression models. ResultsOut of 3986 patients enrolled in the DELTA-2 PCI registry, 2418 were EXCEL candidates and 1568 were not EXCEL candidates. The occurrence of the primary endpoint was higher among non-EXCEL candidates compared with EXCEL candidates (15.4% vs. 6.9%; hazard ratio 2.52; 95% confidence interval 2.00–3.16; p < 0.001). Among 901 patients enrolled in the historical DELTA-1 CABG cohort, 471 were EXCEL candidates and 430 were not EXCEL candidates. When comparing the DELTA-2 PCI with the DELTA-1 CABG cohort, the occurrence of the primary endpoint was lower in the PCI group compared with the historical CABG cohort among EXCEL candidates (6.9% vs. 10.7%; adjusted hazard ratio: 0.65; 95% confidence interval: 0.45–0.92), while no significant difference was observed among non-EXCEL candidates (15.4% vs. 12.5%; adjusted hazard ratio: 0.94; 95% confidence interval: 0.67–1.33) with evidence of statistical interaction (adjusted interaction p-value = 0.002). ConclusionsIn a real-world population, PCI can be selected more favorably as an alternative to CABG in patients fulfilling the enrollment criteria of the EXCEL trial.

Interaction Between Frailty and Access Site in Older Adults Undergoing Transcatheter Aortic Valve Replacement

ObjectivesThe authors sought to determine whether frail older adults undergoing nonfemoral transcatheter aortic valve replacement (TAVR) procedures had a higher risk of 30-day and 12-month mortality. BackgroundFrailty can help predict outcomes and guide therapy in older adults being considered for TAVR. Nonfemoral TAVR procedures are more invasive and impart a greater risk of adverse events, which may be less well tolerated in frail patients, compared with transfemoral TAVR procedures. MethodsThis study was a post hoc analysis of the FRAILTY-AVR (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions) prospective multicenter cohort that consisted of older adults undergoing TAVR from 2012 to 2017. Frailty was assessed using the Essential Frailty Toolset (EFT). Endpoints of interest were 30-day and 12-month all-cause mortality. Interaction tables and multivariable logistic regression models were used to investigate statistical interaction on the additive and multiplicative scales. ResultsThe cohort consisted of 723 patients with a mean age of 84 ± 6 years, of which 556 (77%) had femoral access and 167 (23%) had nonfemoral access. In frail patients with EFT scores ≥3 (35%), nonfemoral access was associated with increased 30-day mortality (odds ratio [OR]: 3.91; 95% confidence interval [CI]: 1.48 to 10.31); whereas in nonfrail patients with EFT scores <3 (65%), nonfemoral access had no effect (OR: 1.29; 95% CI: 0.34 to 4.94). There was statistical evidence of interaction between frailty and access site on 30-day mortality on the additive scale (relative excess risk due to interaction = 5.95). Nonfemoral access was associated with increased 1-year mortality in frail patients (OR: 1.98; 95% CI: 1.00 to 3.93) but not in nonfrail patients (OR: 1.83; 95% CI: 0.90 to 3.74), although there was no statistical evidence of interaction. ConclusionsFrail patients undergoing TAVR via a more invasive nonfemoral access face a substantially higher risk of 30-day mortality, whereas nonfrail older adults tolerate the procedure with a low short-term risk irrespective of access route.

The Combined Influence of Air Pollution and Home Learning Environment on Early Cognitive Skills in Children.

Cognitive skills are one component of school readiness that reflect a child’s neurodevelopment and are influenced by environmental and social factors. Most studies assess the impact of these factors individually, without taking into consideration the complex interactions of multiple factors. The objective of this study was to examine the joint association of markers of environmental pollution and of social factors on early cognitive skills in an urban cohort of children. For this, we chose isophorone in ambient air as a marker of industrial air pollution. Low quality home learning environments was chosen as a marker of the social factors contributing to cognitive development. Using a subpopulation from the Early Childhood Longitudinal Study, Birth Cohort (N = 4050), isophorone exposure was assigned using the 2002 National Air Toxics Assessment. Home learning environment was assessed with a modified version of the Home Observation for Measurement of the Environment (HOME) Inventory, and standardized math assessment scores were used as a measure of early cognitive skills. Multiple linear regression was used to estimate the effect of both exposures on math scores. After adjustment for confounders, children living in areas with ambient isophorone in the upper quintile of exposure (>0.49 ng/m3) had math scores that were 1.63 points lower than their less exposed peers [95% CI: −2.91, −0.34], and children with lower HOME scores (at or below 9 out of 12) had math scores that were 1.20 points lower than children with better HOME scores [95% CI: −2.30, −0.10]. In adjusted models accounting for identified confounders and both exposures of interest, both high isophorone exposure and low HOME score remained independently associated with math scores [−1.48, 95% CI: −2.79, −0.18; −1.05, 95% CI: −2.15, 0.05, respectively]. There was no statistical evidence of interaction between the two exposures, although children with both higher isophorone exposure and a low HOME score had a decrement in math scale score beyond the additive effect of each exposure. This was primarily observed among male children. These findings suggest that aspects of both the physical and social environments are independently associated with children’s early cognitive skills. Future research aiming to improve children’s early cognitive skills and subsequent school readiness should address both domains.

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. National Research Agency on AIDS and Viral Hepatitis (ANRS).

Influence of Cigarette Smoking on Rheumatoid Arthritis Risk in the Han Chinese Population.

Cigarette smoking has been shown in European populations to be associated with rheumatoid arthritis (RA) susceptibility. This study aims to examine the association of smoking with RA in the Han Chinese population. 718 Han Chinese RA patients and 404 healthy controls were studied. The associations of cigarette smoking (current, former or ever vs. never smokers, and pack-years of exposure) with RA, anti-cyclic citrullinated peptide antibody (ACPA) positive RA, IgM rheumatoid factor (RF) positive RA, and baseline radiographic erosions (modified van der Heijde-Sharp scores) were assessed. The interaction between smoking and the HLA-DRB1 shared epitope (SE) in RA was also examined. In this study, 11 (1.53%) cases and 6 (1.49%) controls were former smokers (p = 0.95), while 95 (13.23%) cases and 48 (11.88%) controls were current smokers (p = 0.52). Trends toward associations between smoking status (ever vs. never) with RA-overall (p = 0.15, OR = 1.44), ACPA-positive RA (p = 0.24, OR = 1.37), RF-positive RA (p = 0.14, OR = 1.46), or the presence of radiographic erosions (p = 0.66, OR = 1.28) were observed although individually here were not statistically significant. There was no evidence of statistical interaction between smoking status (ever vs. never) and SE for all RA, ACPA-positive RA, ACPA-negative RA, RF-positive RA, RF-negative RA (p = 0.37, 0.50, 0.24, 0.26, and 0.81 respectively), and the 95% CI for the attributable proportion for all interactions included 0. This is the first study to examine the association of cigarette smoking with RA in the Han Chinese population. This study shows a trend toward an interaction between smoking and SE carriage influencing the risk of RA, though findings were not statistically significant. It is possible that in the presence of universal exposure to heavy air pollution the effect of smoking on RA risk may be obscured.

Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry

ObjectivesThe aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BackgroundEarly DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. MethodsUsing data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. ResultsDuring 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. ConclusionsDAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation.

Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

We examined risks associated with joint exposure of gene variants and pesticides. Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications. Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time. We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A) 106:653-658, 2016. © 2016 Wiley Periodicals, Inc.