- Browse by Author
Browsing by Author "Nan, Hongmei"
Now showing 1 - 10 of 49
Results Per Page
Sort Options
Item A Modified Tumor-Node-Metastasis Classification for Primary Operable Colorectal Cancer(Oxford University Press, 2020-10-16) Zhang, Chundong; Mei, Zubing; Pei, Junpeng; Abe, Masanobu; Zeng, Xiantao; Huang, Qiao; Nishiyama, Kazuhiro; Akimoto, Naohiko; Haruki, Koichiro; Nan, Hongmei; Meyerhardt, Jeffrey A.; Zhang, Rui; Li, Xinxiang; Ogino, Shuji; Ugai, Tomotaka; Community and Global Health, School of Public HealthBackground: The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods: We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results: We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P < .001) and better model fitting (Akaike information criteria = 70 937 vs 71 238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts. Conclusions: The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.Item Aberrant cholesterol metabolism in colorectal cancer represents a targetable vulnerability(Elsevier, 2023-07) Xie, Jingwu; Nguyen, Chi Mai; Turk, Anita; Nan, Hongmei; Imperiale, Thomas F.; House, Michael; Huang, Kun; Su, Jing; Biostatistics, School of Public HealthItem 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 Association between indoor tanning frequency during early life and other potentially addictive behaviors among US women(Elsevier, 2021) Tsibris, Hillary C.; Nan, Hongmei; Li, Xin; Global Health, School of Public HealthItem 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 between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients(Elsevier, 2020-10) Yang, Keming; Forman, Michele R.; Graham, Brett H.; Monahan, Patrick O.; Giovannucci, Edward L.; De Vivo, Immaculata; Chan, Andrew T.; Nan, Hongmei; Epidemiology, School of Public HealthBackground Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival. Methods We examined the association of pre-diagnostic leukocyte mtDNAcn (measured by qPCR) with overall and CRC-specific survival among 587 patients in Nurses’ Health Study and Health Professionals Follow-Up Study. Cox models were constructed to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Results During a mean follow-up of 10.5 years, 395 deaths were identified; 180 were due to CRC. Overall, we did not observe significant associations between mtDNAcn and either overall or CRC-specific survival among all cases or by cancer location, grade, or stage. In an exploratory stratified analysis, a suggestive inverse association of mtDNAcn and overall death risk appeared among current smokers [HR (95 % CI) for 1 SD decrease in mtDNAcn = 1.50 (0.98, 2.32), P-trend = 0.06]. Reduced mtDNAcn and lower CRC-specific death risk was observed among patients aged ≤ 70.5 at diagnosis [HR (95 % CI) for 1 SD decrease of mtDNAcn = 0.71 (0.52, 0.97), P-trend = 0.03], ≤ 5 years from blood collection to diagnosis [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.65 (0.44, 0.96), P-trend = 0.03] and those consuming a low-inflammatory diet [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.61 (0.42, 0.88), P-trend = 0.009]. Conclusion no significant associations between pre-diagnostic leukocyte mtDNAcn and either overall or CRC-specific survival appeared but exploratory analysis identified potential sub-group associations.Item Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival(AME Publishing, 2021-03) Wang, Haijiao; Liu, Hongliang; Dai, Wei; Luo, Sheng; Amos, Christopher I.; Lee, Jeffrey E.; Li, Xin; Yue, Ying; Nan, Hongmei; Wei, Qingyi; Epidemiology, School of Public HealthBackground: Peroxisomes are ubiquitous and dynamic organelles that are involved in the metabolism of reactive oxygen species (ROS) and lipids. However, whether genetic variants in the peroxisome pathway genes are associated with survival in patients with melanoma has not been established. Therefore, our aim was to identify additional genetic variants in the peroxisome pathway that may provide new prognostic biomarkers for cutaneous melanoma (CM). Methods: We assessed the associations between 8,397 common single-nucleotide polymorphisms (SNPs) in 88 peroxisome pathway genes and CM disease-specific survival (CMSS) in a two-stage analysis. For the discovery, we extracted the data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center (MDACC). We then replicated the results in another dataset from the Nurse Health Study (NHS)/Health Professionals Follow-up Study (HPFS). Results: Overall, 95 (11.1%) patients in the MDACC dataset and 48 (11.7%) patients in the NHS/HPFS dataset died of CM. We found 27 significant SNPs in the peroxisome pathway genes to be associated with CMSS in both datasets after multiple comparison correction using the Bayesian false-discovery probability method. In stepwise Cox proportional hazards regression analysis, with adjustment for other covariates and previously published SNPs in the MDACC dataset, we identified 2 independent SNPs (TMEM135 rs567403 C>G and PEX5 rs7969508 A>G) that predicted CMSS (P=0.003 and 0.031, respectively, in an additive genetic model). The expression quantitative trait loci analysis further revealed that the TMEM135 rs567403 GG and PEX5 rs7969508 GG genotypes were associated with increased and decreased levels of mRNA expression of their genes, respectively. Conclusions: Once our findings are replicated by other investigators, these genetic variants may serve as novel biomarkers for the prediction of survival in patients with CM.Item Association of omega-3 and omega-6 fatty acid intake with leukocyte telomere length in US males(Elsevier, 2022-12) Seo, Bojung; Yang, Keming; Kahe, Ka; Qureshi, Abrar A.; Chan, Andrew T.; De Vivo, Immaculata; Cho, Eunyoung; Giovannucci, Edward L.; Nan, Hongmei; Community and Global Health, Richard M. Fairbanks School of Public HealthBackground Omega-3 (n–3) and omega-6 (n–6) fatty acids may contribute to oxidative stress and inflammation, which are related to telomere shortening. Evidence supporting an association between intake of n–3 or n–6 fatty acids and leukocyte telomere length (LTL) in males has been limited. Objectives We conducted a cross-sectional study to examine the associations of total or individual n–3 or total n–6 fatty acid intake with LTL in US males. Methods We included 2,494 US males with LTL measurement from 4 nested case–control studies within the Health Professionals Follow-Up Study. Individuals with previous histories of cancers, diabetes, and cardiovascular diseases at or before blood collection were excluded. Blood collection was performed between 1993 and 1995, and relevant information including n–3 and n–6 intake was collected in 1994 by questionnaire. The LTL was log-transformed and Z scores of the LTL were calculated for statistical analyses by standardizing the LTL in comparison with the mean within each selected nested case–control study. Results We found that consumption of DHA (22:6n–3) was positively associated with LTL. In the multivariable-adjusted model, compared with individuals who had the lowest intake of DHA (i.e., first quartile group), the percentage differences (95% CIs) of LTL were −3.7 (−13.7, 7.5), 7.0 (−4.3, 19.7), and 8.2 (−3.5, 21.3) for individuals in the second, third, and fourth quartiles of consumption, respectively (P-trend = 0.0498). We did not find significant associations between total n–3 or total n–6 fatty acid intakes and LTL. In addition, we found that males who consumed canned tuna had longer LTL than those who did not; in the multivariable-adjusted model, the percentage difference of LTL was 10.5 (95% CI: 1.3, 20.4) (P = 0.02). Conclusions Our results suggest that higher intakes of DHA and canned tuna consumption are associated with longer LTL.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 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.