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Item A Review of Research on Disparities in the Care of Black and White Patients With Cancer in Detroit(Frontiers Media, 2021-07-07) Simon, Michael S.; Raychaudhuri, Sreejata; Hamel, Lauren M.; Penner, Louis A.; Schwartz, Kendra L.; Harper, Felicity W. K.; Thompson, Hayley S.; Booza, Jason C.; Cote, Michele; Schwartz, Ann G.; Eggly, Susan; Epidemiology, Richard M. Fairbanks School of Public HealthRacial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute's (KCI's) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.Item A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO(Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public HealthIntroduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.Item A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer(Hindawi, 2022-07-20) Shao, Changxia; Chang, Michael S.; Lam, Fred C.; Marley, Andrew R.; Tang, Huilin; Song, Yiqing; Miller, Chelsey; Brown, Madeline; Wan, Isabella; Han, Jiali; Adeboyeje, Gboyega; Epidemiology, Richard M. Fairbanks School of Public HealthPatients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.6-0.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.1-3.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.8-3.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43-1.02) for OS with HRD+ vs. HRD-. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7-1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.Item Age, inflammation, alkaline phosphatase, and coronary artery calcification in firefighters(Springer Nature, 2025-04-23) Li, Mingyue; Han, Jiali; Muegge, Carolyn; Zollinger, Terrell; Zhou, Laura Y.; Monahan, Patrick; Wessel, Jennifer; Kleinschmidt, Vanessa; Moffatt, Steven; Nan, Hongmei; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Firefighting involves exposure to hazardous conditions that may contribute to adverse long term health outcomes, including cardiovascular disease. While coronary artery disease (CAD) is a leading cause of morbidity among firefighters, the specific occupational contributions to Coronary Artery Calcification (CAC), a reliable predictor of CAD, are not well understood. Methods: We conducted a cross-sectional study involving 410 firefighters, aged 35-68, who underwent comprehensive health assessments, including CAC measurement using computed tomography. Multiple logistic regression models were built to examine the associations of demographic, lifestyle, and clinical variables with CAC score. Results: Our analysis revealed statistically significant associations between several clinical indicators and CAC score. Age (odds ratio (OR): 1.12; 95% confidence interval (95% CI): [1.05, 1.19]) and percentage of monocytes (OR: 1.29; 95% CI: [1.06, 1.58]) were positively correlated with higher CAC score, highlighting the role of inflammation in CAD among firefighters. Moreover, the enzyme alkaline phosphatase emerged as an independent predictor of CAC score (OR: 1.02; 95% CI: [1.01, 1.04]), suggesting a novel biomarker of cardiovascular risk in this population. Conclusion: Our study identified several risk factors associated with increased CAC score in firefighters, including age, inflammation, and alkaline phosphatase. These findings underscore the importance of tailored health monitoring and interventions to mitigate CAD risk in firefighters, considering both general and occupation-specific risk factors. This study contributes to a better understanding of the occupational health challenges faced by firefighters and provides a foundation for future research and preventive strategies in this high-risk group.Item Analyzing Perceptions of Community-Engaged Health Research Partnerships Comprising Hispanic Groups and Academic Allies in Indiana(IUI Office of Community Engagement, 2022) Gil, Cindy; Armenta, Karla; Espada, Camila; Ontiveros-Salinas, Leonel; Maupome, Gerardo; Epidemiology, Richard M. Fairbanks School of Public HealthObjectives: To analyze perceptions about multiple community-engaged oral health research partnerships with various local Hispanic-serving institutions and community-based organizations occurring in Indiana from 2010 through 2020, via interviews with actors involved in those partnerships. Methods: We designed key informant interview questions based on a literature review to inform the approach at synthesizing perspectives from community partners and academic allies. Statements were categorized using thematic analysis and grounded theory. Lessons Learned: Forty percent of respondents stated that community-engaged research projects connect communities with educational information about dental care and low-cost resources. In terms of capacity building, about half of respondents felt these projects had a positive impact. Conclusions: Community partners defined positive impact as increasing access to dental care educational resources, helping to enhance communication networks through social media with community partners, and contributing to local Hispanic health education through TV, internet, and radio partnerships. The partnerships uniting Hispanic groups and academic allies appear to have helped set a foundation of trust to support current and future efforts in Indiana.Item Assessing Progress Toward the Vision of a Comprehensive, Shared Electronic Care Plan: Scoping Review(JMIR, 2022-06-10) Norton, Jenna M.; Ip, Alex; Ruggiano, Nicole; Abidogun, Tolulope; Camara, Djibril Souleymane; Fu, Helen; Hose, Bat-Zion; Miran, Saadia; Hsiao, Chun-Ju; Wang, Jing; Bierman, Arlene S.; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Care plans are central to effective care delivery for people with multiple chronic conditions. But existing care plans-which typically are difficult to share across care settings and care team members-poorly serve people with multiple chronic conditions, who often receive care from numerous clinicians in multiple care settings. Comprehensive, shared electronic care (e-care) plans are dynamic electronic tools that facilitate care coordination and address the totality of health and social needs across care contexts. They have emerged as a potential way to improve care for individuals with multiple chronic conditions. Objective: To review the landscape of e-care plans and care plan-related initiatives that could allow the creation of a comprehensive, shared e-care plan and inform a joint initiative by the National Institutes of Health and the Agency for Healthcare Research and Quality to develop e-care planning tools for people with multiple chronic conditions. Methods: We conducted a scoping review, searching literature from 2015 to June 2020 using Scopus, Clinical Key, and PubMed; we also searched the gray literature. To identify initiatives potentially missing from this search, we interviewed expert informants. Relevant data were then identified and extracted in a structured format for data synthesis and analysis using an expanded typology of care plans adapted to our study context. The extracted data included (1) the perspective of the initiatives; (2) their scope, (3) network, and (4) context; (5) their use of open syntax standards; and (6) their use of open semantic standards. Results: We identified 7 projects for e-care plans and 3 projects for health care data standards. Each project provided critical infrastructure that could be leveraged to promote the vision of a comprehensive, shared e-care plan. All the e-care plan projects supported both broad goals and specific behaviors; 1 project supported a network of professionals across clinical, community, and home-based networks; 4 projects included social determinants of health. Most projects specified an open syntax standard, but only 3 specified open semantic standards. Conclusions: A comprehensive, shared, interoperable e-care plan has the potential to greatly improve the coordination of care for individuals with multiple chronic conditions across multiple care settings. The need for such a plan is heightened in the wake of the ongoing COVID-19 pandemic. While none of the existing care plan projects meet all the criteria for an optimal e-care plan, they all provide critical infrastructure that can be leveraged as we advance toward the vision of a comprehensive, shared e-care plan. However, critical gaps must be addressed in order to achieve this vision.Item Association between plasma L-carnitine levels and mitochondrial DNA copy number(Springer Nature, 2023-12-11) Li, Mingyue; Yang, Keming; De Vivo, Immaculata; Eliassen, A. Heather; Qureshi, Abrar A.; Nan, Hongmei; Han, Jiali; Epidemiology, Richard M. Fairbanks School of Public HealthMitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = −0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.Item Association of sun-seeking behaviors with indoor tanning behavior in US white females during high school/college in Nurses' Health Study II(Springer Nature, 2024-01-11) Seo, Bojung; Yang, Sheng; Cho, Eunyoung; Qureshi, Abrar A.; Han, Jiali; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Frequent exposure to ultraviolet light has more detrimental and longer-term effects on the skin in early life than in adulthood. Teenagers with strong sun-seeking behaviors may be more likely to use an indoor tanning bed than those who seek less sun. We aimed to examine associations between sun-seeking behaviors and indoor tanning behavior during high school/college in US females. Methods: In this cross-sectional study, we used data from The Nurses' Health Study II, a large prospective cohort of US female nurses. We included a total of 81,746 white females who provided responses on the average annual frequency of indoor tanning during high school/college. Our study exposures were number of times/week spent outdoors in a swimsuit and percentage of time wearing sunscreen at the pool/beach as a teenager, weekly hours spent outdoors in direct sunlight during the daytime during high school/college, and number of severe sunburns that blistered between ages 15-20 years. The main outcome was annual frequency of indoor tanning bed usage during high school/college. Results: In multivariable-adjusted logistic regression, we demonstrated positive associations between sun-seeking behaviors and indoor tanning use. Specifically, teenagers who spent 7 times/week outdoors in a swimsuit (adjusted odds ratio [aOR], 95% confidence interval [CI] for daily vs. <1/week: 2.68, 1.76-4.09) were more likely to use indoor tanning beds ≥ 12 times/year. Teenagers with ≥ 10 sunburns (aOR, 95% CI for ≥ 10 vs. never: 2.18, 1.53-3.10) were more likely to use indoor tanning beds ≥ 12 times/year. Also, teenagers/undergraduates who spent ≥ 5 h/week outdoors in direct sunlight (aOR, 95% CI for ≥ 5 h/week vs. <1 h/week: 2.18, 1.39-3.44) were more likely to use indoor tanning ≥ 12 times/year. However, there was not a significant association between average usage of sunscreen at the pool/beach and average usage of indoor tanning beds. Multivariable-adjusted linear regression models also showed similar results. Conclusions: Teenagers who spent more time outdoors in a swimsuit/direct sunlight or got more sunburns tended to use indoor tanning more frequently. These findings provide evidence that teenagers with stronger sun-seeking behaviors may have more exposure to artificial ultraviolet radiation as well.Item Associations between serum micronutrients and all-cause, cancer, and cardiovascular mortality in a national representative population: Mediated by inflammatory biomarkers(Elsevier, 2025) Liu, Chunliang; Wongsonegoro, Harrison; Sheng, Tianchen; Fan, Hao; Zhang, Jianjun; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Micronutrient intake was inversely associated with cancer and cardiovascular risk in previous studies, but obtained results were inconsistent and the biological mechanisms for this potential protective effect remain elusive. Therefore, we investigated the associations of serum vitamin C, 25(OH)D, α-tocopherol, β-carotene, lycopene, folate, and iron with all-cause, cancer, and cardiovascular mortality. We further evaluated whether these associations were mediated through altered inflammatory responses. Methods: Data were obtained from 11,539 participants aged ≥40 years in the National Health and Nutrition Examination Survey (NHANES) in 2001-2006 and 2017-2018. Mortality status of the participants with an average follow-up of 10.5 years was ascertained from the linked mortality files of the National Death Index. Cox proportional hazards regression was performed to evaluate mortality risk in relation to serum micronutrients, while mediation analysis was used to assess the mediating effects of serum C-reactive protein and white blood cell count on the associations of interest. Results: After adjustment for confounders, serum levels of vitamin C, 25(OH)D, β-carotene, and lycopene were associated with a reduced risk of death from all causes, cancer, and cardiovascular disease. For example, HRs (95 % CIs) for quartiles 2, 3, and 4 vs. quartile 1 of 25(OH)D were, respectively, 0.72 (0.62, 0.83), 0.70 (0.62, 0.79), and 0.66 (0.56, 0.78) (p-trend: <0.0001) for all-cause mortality, 0.68 (0.52, 0.91), 0.54 (0.39, 0.73), and 0.48 (0.32, 0.71) (p-trend: 0.0001) for cancer mortality, and 0.64 (0.50, 0.83), 0.66 (0.53, 0.83), and 0.59 (0.42, 0.82) (p-trend: 0.0012) for cardiovascular mortality. Additionally, serum C-reactive protein significantly mediated 5.3%-20.4 %, 4.5%-18.1 %, and 3.3%-15.7 % of the associations of vitamin C, 25(OH)D, β-carotene, and lycopene with all-cause, cancer, and cardiovascular mortality, respectively. Conclusion: This study suggested that serum levels of several antioxidants and vitamin D were inversely associated with all-cause, cancer, and cardiovascular mortality, mediated in part by mitigated inflammatory responses.Item Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region(American Association for Cancer Research, 2022) Jordahl, Kristina M.; Shcherbina, Anna; Kim, Andre E.; Su, Yu-Ru; Lin, Yi; Wang, Jun; Qu, Conghui; Albanes, Demetrius; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D.; Budiarto, Arif; Campbell, Peter T.; Carreras-Torres, Robert; Casey, Graham; Cenggoro, Tjeng Wawan; Chan, Andrew T.; Conti, David V.; Dampier, Christopher H.; Devall, Matthew A.; Díez-Obrero, Virginia; Dimou, Niki; Drew, David A.; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Gruber, Stephen B.; Gsur, Andrea; Gunter, Marc J.; Hampel, Heather; Harlid, Sophia; Harrison, Tabitha A.; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R.; Jenkins, Mark A.; Joshi, Amit D.; Keku, Temitope O.; Larsson, Susanna C.; Le Marchand, Loic; Lewinger, Juan Pablo; Li, Li; Mahesworo, Bharuno; Moreno, Victor; Morrison, John L.; Murphy, Neil; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Obón-Santacana, Mireia; Ogino, Shuji; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Peoples, Anita R.; Pharoah, Paul D. P.; Platz, Elizabeth A.; Potter, John D.; Prentice, Ross L.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Scacheri, Peter C.; Schmit, Stephanie L.; Schoen, Robert E.; Slattery, Martha L.; Stern, Mariana C.; Tangen, Catherine M.; Thibodeau, Stephen N.; Thomas, Duncan C.; Tian, Yu; Tsilidis, Konstantinos K.; Ulrich, Cornelia M.; van Duijnhoven, Franzel J. B.; Van Guelpen, Bethany; Visvanathan, Kala; Vodicka, Pavel; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Zemlianskaia, Natalia; Chang-Claude, Jenny; Gauderman, W. James; Hsu, Li; Kundaje, Anshul; Peters, Ulrike; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.