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Item Major Occupations and Private Insurance of Working Postpartum Women in Poverty in the United States, 2019(Mary Ann Liebert, 2023-10-18) Seo, Bojung; Nan, Hongmei; Epidemiology, School of Public HealthBackground: Although working postpartum women in poverty still have unmet medical needs, relevant research is lacking. Thus, we aimed to determine the five most frequent occupations of U.S. postpartum women in poverty and further examine whether the most frequent occupations are associated with poverty/being uninsured by an employer. Methods: This is a cross-sectional study. We included women who had a job and gave birth within the last 12 months from a 2019 American Community Survey Public Use Microdata Sample. To examine the associations between the most frequent occupations and being in poverty/uninsured through an employer/union, we used age- and race-adjusted and multivariable-adjusted logistic regression models. Results: A total of 14.3% of working postpartum women lived in poverty, and their most frequent major occupations were sales and related work, followed by food preparation and serving-related work, office and administrative support work, health care support work, and cleaning and ground maintenance. A total of 51.2% of women in the most frequent major occupations were uninsured through an employer/union. Compared with women in other occupations, women in the most frequent major occupations had fewer working hours and weeks that included paid leave. In particular, cleaners and ground maintenance workers and food preparation and serving-related workers were most likely to be in poverty and uninsured through an employer/union. Conclusions: Compared with other occupations, the most frequent occupations were more likely to be insecure and less likely to provide health insurance. Our U.S.-based study suggested that current policies regarding employee benefits needed to be improved especially for the most frequent major occupations.Item The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women(MDPI, 2023-10-04) Lawson, Andrew B.; Kim, Joanne; Johnson, Courtney; Ratnapradipa, Kendra L.; Alberg, Anthony J.; Akonde, Maxwell; Hastert, Theresa; Bandera, Elisa V.; Terry, Paul; Mandle, Hannah; Cote, Michele L.; Bondy, Melissa; Marks, Jeffrey; Peres, Lauren C.; Schildkraut, Joellen; Peters, Edward S.; Epidemiology, School of Public HealthBackground: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. Methods: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. Results: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. Conclusions: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen.Item The magnesium global network (MaGNet) to promote research on magnesium in diseases focusing on covid-19(JLE, 2021) Wolf, Federica I.; Maier, Jeanette A.; Rosanoff, Andrea; Barbagallo, Mario; Baniasadi, Shadi; Castiglioni, Sara; Cheng, Fu-Chou; Colaneri Day, Sherrie; Costello, Rebecca B.; Dominguez, Ligia J.; Elin, Ronald J.; Gamboa-Gomez, Claudia; Guerrero-Romero, Fernando; Kahe, Ka; Kisters, Klaus; Kolisek, Martin; Kraus, Anton; Iotti, Stefano; Mazur, Andre; Mercado-Atri, Moises; Merolle, Lucia; Micke, Oliver; Gletsu-Miller, Nana; Nielsen, Forrest; O-Uchi, Jin; Piazza, Ornella; Plesset, Michael; Pourdowlat, Guitti; Rios, Francisco J.; Rodriguez-Moran, Martha; Scarpati, Giuliana; Shechter, Michael; Song, Yiqing; Spence, Lisa A.; Touyz, Rhian M.; Trapani, Valentina; Veronese, Nicola; von Ehrlich, Bodo; Vormann, Juergen; Wallace, Taylor C.; CMER Center for Magnesium Education, Research; Gesellschaft für Magnesium-Forschung e.V. Germany; SDRM Society (International Society for the Development of Research on Magnesium); Epidemiology, School of Public HealthItem Characteristics of Veterans with non-VA encounters enrolled in a trial of standards-based, interoperable event notification and care coordination(American Board of Family Medicine, 2021) Kartje, Rebecca; Dixon, Brian E.; Schwartzkopf, Ashley L.; Guerrero, Vivian; Judon, Kimberly M.; Yi, Joanne C.; Boockvar, Kenneth; Epidemiology, School of Public HealthIntroduction: Understanding how veterans use Veterans Affairs (VA) for primary care and non-VA for acute care can help policy makers predict future health care resource use. We aimed to describe characteristics of veterans enrolled in a multisite clinical trial of non-VA acute event notifications and care coordination and to identify patient factors associated with non-VA acute care. Methods: Characteristics of 565 veterans enrolled in a prospective cluster randomized trial at the Bronx and Indianapolis VA Medical Centers were obtained by interview and chart review. Results: Veterans' mean age was 75.8 years old, 98.3% were male, and 39.2% self-identified as a minority race; 81.2% reported receiving the majority of care at the VA. There were 197 (34.9%) veterans for whom a non-VA acute care alert was received. Patient characteristics significantly associated with greater odds of a non-VA alert included older age (OR = 1.05; 95% CI, 1.04-1.05); majority of care received is non-VA (OR = 1.83; 95% CI, 1.06-3.15); private insurance (OR = 1.39; 95% CI, 1.19-1.62); and higher income (OR = 4.01; 95% CI, 2.68-5.98). Conclusions: We identified several patient-level factors associated with non-VA acute care that can inform the design of VA services and policies for veterans with non-VA acute care encounters and reintegration back into the VA system.Item Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study(Elsevier, 2021) Tsilidis, Konstantinos K.; Papadimitriou, Nikos; Dimou, Niki; Gill, Dipender; Lewis, Sarah J.; Martin, Richard M.; Murphy, Neil; Markozannes, Georgios; Zuber, Verena; Cross, Amanda J.; Burrows, Kimberley; Lopez, David S.; Key, Timothy J.; Travis, Ruth C.; Perez-Cornago, Aurora; Hunter, David J.; van Duijnhoven, Fränzel J. B.; Albanes, Demetrius; Arndt, Volker; Berndt, Sonja I.; Bézieau, Stéphane; Bishop, D. Timothy; Boehm, Juergen; Brenner, Hermann; Burnett-Hartman, Andrea; Campbell, Peter T.; Casey, Graham; Castellví-Bel, Sergi; Chan, Andrew T.; Chang-Claude, Jenny; de la Chapelle, Albert; Figueiredo, Jane C.; Gallinger, Steven J.; Giles, Graham G.; Goodman, Phyllis J.; Gsur, Andrea; Hampe, Jochen; Hampel, Heather; Hoffmeister, Michael; Jenkins, Mark A.; Keku, Temitope O.; Kweon, Sun-Seog; Larsson, Susanna C.; Le Marchand, Loic; Li, Christopher I.; Li, Li; Lindblom, Annika; Martín, Vicente; Milne, Roger L.; Moreno, Victor; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Offit, Kenneth; Pharoah, Paul D. P.; Platz, Elizabeth A.; Potter, John D.; Qi, Lihong; Rennert, Gad; Sakoda, Lori C.; Schafmayer, Clemens; Slattery, Martha L.; Snetselaar, Linda; Schenk, Jeanette; Thibodeau, Stephen N.; Ulrich, Cornelia M.; Van Guelpen, Bethany; Harlid, Sophia; Visvanathan, Kala; Vodickova, Ludmila; Wang, Hansong; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Zheng, Wei; Bueno-de-Mesquita, Bas; Boutron-Ruault, Marie-Christine; Hughes, David J.; Jakszyn, Paula; Kühn, Tilman; Palli, Domenico; Riboli, Elio; Giovannucci, Edward L.; Banbury, Barbara L.; Gruber, Stephen B.; Peters, Ulrike; Gunter, Marc J.; Epidemiology, School of Public HealthBackground: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.Item Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color(American Association for the Advancement of Science, 2021-03-10) Simcoe, Mark; Valdes, Ana; Liu, Fan; Furlotte, Nicholas A.; Evans, David M.; Hemani, Gibran; Ring, Susan M.; Smith, George Davey; Duffy, David L.; Zhu, Gu; Gordon, Scott D.; Medland, Sarah E.; Vuckovic, Dragana; Girotto, Giorgia; Sala, Cinzia; Catamo, Eulalia; Concas, Maria Pina; Brumat, Marco; Gasparini, Paolo; Toniolo, Daniela; Cocca, Massimiliano; Robino, Antonietta; Yazar, Seyhan; Hewitt, Alex; Wu, Wenting; Kraft, Peter; Hammond, Christopher J.; Shi, Yuan; Chen, Yan; Zeng, Changqing; Klaver, Caroline C. W.; Uitterlinden, Andre G.; Ikram, M. Arfan; Hamer, Merel A.; van Duijn, Cornelia M.; Nijsten, Tamar; Han, Jiali; Mackey, David A.; Martin, Nicholas G.; Cheng, Ching-Yu; 23andMe Research Team; International Visible Trait Genetics Consortium; Hinds, David A.; Spector, Timothy D.; Kayser, Manfred; Hysi, Pirro G.; Epidemiology, School of Public HealthHuman eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.Item Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation(Springer Nature, 2021-03-02) Wang, Kang; Li, Zhuyue; Chen, Xingxing; Zhang, Jianjun; Xiong, Yongfu; Zhong, Guochao; Shi, Yang; Li, Qing; Zhang, Xiang; Li, Hongyuan; Xiang, Tingxiu; Foukakis, Theodoros; Radivoyevitch, Tomas; Ren, Guosheng; Epidemiology, School of Public HealthThe increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975–2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted.Item Young Adult Cancer Survivorship: Recommendations for Patient Follow-up, Exercise Therapy, and Research(Oxford University Press, 2020-10-28) Adams, Scott C.; Herman, Jennifer; Lega, Iliana C.; Mitchell, Laura; Hodgson, David; Edelstein, Kim; Travis, Lois B.; Sabiston, Catherine M.; Thavendiranathan, Paaladinesh; Gupta, Abha A.; Epidemiology, School of Public HealthSurvivors of adolescent and young adult cancers (AYAs) often live 50 to 60 years beyond their diagnosis. This rapidly growing cohort is at increased risk for cancer- and treatment-related 'late effects' that persist for decades into survivorship. Recognition of similar issues in pediatric cancer survivors has prompted the development of evidence-based guidelines for late effects screening and care. However, corresponding evidence-based guidelines for AYAs have not been developed. We hosted an AYA survivorship symposium for a large group of multidisciplinary AYA stakeholders (approximately 200 were in attendance) at Princess Margaret Cancer Centre (Toronto, Ontario, Canada) to begin addressing this disparity. The following overview briefly summarizes and discusses the symposium's stakeholder-identified high-priority targets for late effects screening and care and highlights knowledge gaps to direct future research in the field of AYA survivorship. This overview, although not exhaustive, is intended to stimulate clinicians to consider these high-priority screening and care targets when seeing survivors in clinical settings and, ultimately, to support the development of evidence-based late effects screening and care guidelines for AYAs.Item Typical phthalic acid esters induce apoptosis by regulating the PI3K/Akt/Bcl-2 signaling pathway in rat insulinoma cells(Elsevier, 2021) Li, Liping; Wang, Faxuan; Zhang, Jianjun; Wang, Kai; De, Xiaoming; Li, Ling; Zhang, Yuhong; Epidemiology, School of Public HealthDi-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are representative phthalic acid esters (PAEs), a class of environmental endocrine disruptors used as plasticizers. PAEs exposure is associated with glucose metabolism, insulin resistance, and glucose tolerance; however, the mechanism and various PAE effects on human glucose metabolism remain largely unknown. In this study, we investigated the effects of DEHP, DBP, and their mixture on rat insulinoma (INS-1) cell apoptosis and the mechanism involved in vitro. The INS-1 cells were cultured in RPMI-1640 + 10% fetal bovine serum for 24 h and pretreated with dimethyl sulfoxide (vehicle, <0.1%), DEHP (30 μM), DBP (30 μM), and their mixture (30 μM DEHP + 30 μM DBP). The methyl-thiazolyl tetrazolium bromide test was used to measure cell viability. Hoechst 33342/propidium iodide (PI) staining and Annexin V-FITC/PI staining, 2',7'-dichlorofluorescein diacetate assay, and glucose-induced insulin secretion assay were used to detect cell apoptosis rates, intracellular reactive oxygen species (ROS), and insulin secretion in INS-1, respectively. The mRNA expression levels of Bcl-2, Bax, Caspase 9, Caspase 8, Caspase 3, phosphoinositide 3-kinase (PI3K), and Akt were detected using real-time quantitative reverse transcription PCR; their protein expression levels were detected using western blotting. To the best of our knowledge, this study was the first to show that the combined effect of the two PAEs promotes a ROS-mediated PI3K/Akt/Bcl-2 pathway-induced pancreatic β cell apoptosis that is significantly higher than the effects of each PAE. Thus, safety standards and studies do not consider this effect as a significant oversight when blending PAEs. We assert that this must be addressed and corrected for establishing more impactful and safer standards.Item Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants(Oxford University Press, 2021) Campbell, Peter T.; Lin, Yi; Bien, Stephanie A.; Figueiredo, Jane C.; Harrison, Tabitha A.; Guinter, Mark A.; Berndt, Sonja I.; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Gallinger, Steven J.; Gapstur, Susan M.; Giles, Graham G.; Giovannucci, Edward; Gruber, Stephen B.; Gunter, Marc; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Marchand, Loic Le; Li, Li; McLaughlin, John R.; Murphy, Neil; Milne, Roger L.; Newcomb, Polly A.; Newton, Christina; Ogino, Shuji; Potter, John D.; Rennert, Gad; Rennert, Hedy S.; Robinson, Jennifer; Sakoda, Lori C.; Slattery, Martha L.; Song, Yiqing; White, Emily; Woods, Michael O.; Casey, Graham; Hsu, Li; Peters, Ulrike; Epidemiology, School of Public HealthBackground: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.