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Browsing by Author "Han, Jiali"
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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 Addressing disparities in delivery of cancer care for patients with melanoma brain metastases—Not just a simple case of rurality(Society for NueroOncology, 2023-09-28) Riggs, Joseph; Ahn, Hyejeong; Longmoore, Hailee; Jardim, Pedro; Kim, Min J.; Kasper, Ekkehard M.; Han, Jiali; Lam, Fred C.Item Alcohol intake is associated with increased risk of squamous cell carcinoma of the skin: three US prospective cohort studies(Taylor & Francis, 2016-05) Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung; Nijsten, Tamar; Qureshi, Abrar; Department of Epidemiology, School of Public HealthThe association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RRs) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13-1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09-1.59). We found no increased risk of cSCC with other alcoholic beverages. The population-attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC.Item Association Between Built Environment or Health Behavior and Good Health Status Using ACSM American Fitness Index® Data Between 2018 and 2022(2023-12) Seo, Bojung; Han, Jiali; Nan, Hongmei; Monahan, Patrick O.; Duszynski, Thomas J.The US cities still have room for improvement in residents’ health and there are significant differences in general health measures between the cities. High quality environment assets and personal healthier behaviors of residents were known as factors related to better health. Because both sufficient sleep and higher level of personal physical activity are well-known indicators to attain optimal health of individuals, city-level measures of resident health behaviors, such as sleep quantity, and environmental assets that support physical activity may jointly improve residents’ general health. Further, sufficient sleep may mediate the effect of activity-related environmental factors on general health. However, evidence regarding such associations at the city level is lacking. The American College of Sports Medicine (ACSM) American Fitness Index® (AFI) data currently provide both environment assets and health indicators for the 100 largest US cities. The aim of this research was to test the following three hypotheses using the 2018 to 2022 AFI data. First, the association between environment indicators of cities and good health status of residents was examined. Second, the association between personal health behaviors of residents and good health status was also examined. Lastly, the moderating or mediating effect of sleep on the association between significant environmental factors and good health status was examined. This study discovered that activity-related environment factors, such as availability of parks within a 10-minute walk, Walk Score®, Bike Score®, and adoption of Complete Streets policy, were significantly associated with the self-reported general health status of residents. This study also demonstrated all measured healthy behaviors including meeting physical activity guidelines, using active transport to work, sufficient intake of fruits and vegetables, sufficient sleep, and non-smoking were positively related to general health status of city residents. This study also identified the synergistic interaction between sufficient daily sleeping and environment factors related to the level of physical activity on residents’ good health status. Overall, these findings will provide evidence for better understanding the health-related unmet needs of residents in US cities, and also create valuable context and support for development and targeting of more efficacious public health interventions and messaging.Item The Association Between Citrus Consumption and Skin Cancer: An Analysis of Risk and Nutrient-Gene Interaction(2020-12) Marley, Andrew Raymond; Han, Jiali; Sibg, Yiqing; Li, Xin; Li, Ming; Champion, Victoria L.Purpose. In the US, melanoma and non-melanoma skin cancer (NMSC) rates have increased substantially in recent decades. While many skin cancer risk factors have been established, the impact of dietary citrus, which is naturally abundant in photocarcinogenic psoralens, remains enigmatic. The purpose of this research was to investigate associations between citrus consumption and risks of melanoma and NMSC, and to conduct a genome-wide study to identify genetic variants that may modify this association. Methods. Participants from the UK Biobank were leveraged for these analyses. Citrus consumption was collected via five rounds of 24-hour recall questionnaires, with complete citrus data available for n=210,126 participants. Ascertainment of melanoma and NMSC cases were identified by international classification of disease codes via linkage with national registries. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between citrus consumption and skin cancer outcomes. Individual citrus products were assessed for independent associations with skin cancer risk, and established skin cancer risk factors were tested for interaction. Joint 2-degree-of-freedom (df) and 1-df tests were used to assess interaction between total citrus consumption and genetic variants. Results. After controlling for covariates, high total citrus consumption was significantly associated with increased melanoma risk, an association primarily driven by orange and orange juice consumption. Skin color was found to be a significant effect modifier for the association between total citrus consumption and melanoma risk, but only before adjusting for multiple comparisons. No significant associations were observed for high total citrus consumption or consumption of any individual citrus products and NMSC risk. Significant associations for half a serving of citrus consumption and NMSC risk were likely due to chance or confounding. Index SNPs on chromosomes 3, 9, and 16 were significant according to the joint 2-df test, and 7 SNPs on chromosome 16 displayed evidence of a citrus-gene interaction. Conclusion. My analyses provide evidence in support of high citrus consumption significantly increasing risk of melanoma, but not NMSC. I also identified SNPs on AFG3L1P that may modify this association. Future research should further explore these associations, particularly for NMSC and to confirm my genetic findings.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 Association study of genetic variation in DNA repair pathway genes and risk of basal cell carcinoma(Wiley, 2017-09-01) Lin, Yuan; Chahal, Harvind S.; Wu, Wenting; Cho, Hyunje G.; Ransohoff, Katherine J.; Song, Fengju; Tang, Jean Y.; Sarin, Kavita Y.; Han, Jiali; Epidemiology, School of Public HealthDNA repair plays a critical role in protecting the genome from ultraviolet radiation and maintaining the genomic integrity of cells. Genetic variants in DNA repair-related genes can influence an individual's DNA repair capacity, which may be related to the risk of developing basal cell carcinoma (BCC). We comprehensively assessed the associations of 2,965 independent single-nucleotide polymorphisms (SNPs) across 165 DNA repair pathway genes with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified three SNPs (rs2805831 upstream of XPA: OR = 0.93, P = 1.35 × 10-6 ; rs659857 in exon of MUS81: OR = 1.06, P = 3.09 × 10-6 and rs57343616 in 3' UTR of NABP2: OR = 1.11, P = 6.47 × 10-6 ) as significantly associated with BCC risk in meta-analysis, and all of them were nominally significant in both data sets. Furthermore, rs659857 [T] was significantly associated with decreased expression of MUS81 mRNA in the expression quantitative trait locus (eQTL) analysis. Our findings suggest that the inherited common variation in three DNA repair genes-XPA, MUS81 and NABP2-may be involved in the development of BCC. To our knowledge, our study is the first report thoroughly examining the effects of SNPs across DNA repair pathway genes on BCC risk based on a genome-wide association meta-analysis.Item Associations Between Vitamin D Biomarkers and Cardiometabolic Outcomes Among Women(2020-02) Xia, Jin; Song, Yiqing; Nan, Hongmei; Tu, Wanzhu; Han, JialiThere is growing evidence that vitamin D endocrine system may be associated with multiple cardiometabolic outcomes, such as gestational diabetes mellitus (GDM), type 2 diabetes, and other relevant cardiometabolic comorbidities, as well as some intermediate cardiometabolic biomarkers. African Americans tend to have lower 25-hydroxyvitamin D[25(OH)D] levels and higher cardiometabolic risk than whites. However, the temporal relation between vitamin D status and cardiometabolic outcomes remains unclear due to the lack of longitudinal data. Further, whether adding information on parathyroid hormone (PTH) can explain black-white disparities in cardiometabolic health is unknown. In this dissertation, I first prospectively and longitudinally investigated vitamin D status during early to mid-pregnancy in relation to GDM risk in a multiracial cohort of women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort. I also analyzed the data from the Women’s Health Initiative-Observational Study to 1) cross-sectionally examine race (black-white)-specific linear and non-linear relations of 25(OH)D and PTH with a panel of cardiometabolic biomarkers, including high-sensitive C-reactive protein, estimated glomerular filtration rate, and homeostatic model assessment of insulin resistance and beta-cell function, and 2) cross-sectionally and prospectively evaluate the combined associations of 25(OH)D and PTH with risk of diabetes and related cardiometabolic comorbidities (obesity, hypertension, chronic kidney disease, and cardiovascular disease) in U.S. white and black postmenopausal women. This research provides evidence of the temporal association between vitamin D status and cardiometabolic risk among women from racially/ethnically diverse groups, and possible black-white differences in these associations. The findings enhance our understanding of the contribution of vitamin D-PTH endocrine system to racial disparities in cardiometabolic health.Item Bayesian Adaptive Designs for Early Phase Clinical Trials(2023-07) Guo, Jiaying; Zang, Yong; Han, Jiali; Zhao, Yi; Ren, JieDelayed toxicity outcomes are common in phase I clinical trials, especially in oncology studies. It causes logistic difficulty, wastes resources, and prolongs the trial duration. We propose the time-to-event 3+3 (T-3+3) design to solve the delayed outcome issue for the 3+3 design. We convert the dose decision rules of the 3+3 design into a series of events. A transparent yet efficient Bayesian probability model is applied to calculate the event happening probabilities in the presence of delayed outcomes, which incorporates the informative pending patients' remaining follow-up time into consideration. The T-3+3 design only models the information for the pending patients and seamlessly reduces to the conventional 3+3 design in the absence of delayed outcomes. We further extend the proposed method to interval 3+3 (i3+3) design, an algorithm-based phase I dose-finding design which is based on simple but more comprehensive rules that account for the variabilities in the observed data. Similarly, the dose escalation/deescalation decision is recommended by comparing the event happening probabilities which are calculated by considering the ratio between the averaged follow-up time for at-risk patients and the total assessment window. We evaluate the operating characteristics of the proposed designs through simulation studies and compare them to existing methods. The umbrella trial is a clinical trial strategy that accommodates the paradigm shift towards personalized medicine, which evaluates multiple investigational drugs in different subgroups of patients with the same disease. A Bayesian adaptive umbrella trial design is proposed to select effective targeted agents for different biomarker-based subgroups of patients. To facilitate treatment evaluation, the design uses a mixture regression model that jointly models short-term and long-term response outcomes. In addition, a data-driven latent class model is employed to adaptively combine subgroups into induced latent classes based on overall data heterogeneities, which improves the statistical power of the umbrella trial. To enhance individual ethics, the design includes a response-adaptive randomization scheme with early stopping rules for futility and superiority. Bayesian posterior probabilities are used to make these decisions. Simulation studies demonstrate that the proposed design outperforms two conventional designs across a range of practical treatment-outcome scenarios.