Browsing by Author "Yang, Keming"
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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 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 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 An Epidemiological Review of Diet and Cutaneous Malignant Melanoma(AACR, 2018-10) Yang, Keming; Fung, Teresa T.; Nan, Hongmei; Epidemiology, School of Public HealthIncidence of cutaneous malignant melanoma has continued to rise despite public efforts to promote sun protection behaviors among populations at risk. However, dietary factors may also affect the development of melanoma. In the past few decades, findings from epidemiologic and experimental research have linked consumption of several foods and other nutrients to the risk of melanoma. Caffeine has been associated with a lower risk of melanoma, and citrus fruits and alcohol with increased risk. Associations between polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D with melanoma remain controversial. Diet likely influences melanoma development through several potential mechanisms, such as enhancing UV-induced apoptosis and increasing photosensitivity. We conducted a narrative review to summarize recent epidemiologic studies of diet and melanoma based on published literature. Given the high prevalence of the food items and nutrients covered in this review and the decades-long rising melanoma incidence worldwide, the associations we discuss may have important public health implications in terms of reducing melanoma incidence through dietary modification.Item Genetic variants of EML1 and HIST1H4E in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival(e-Century Publishing, 2021-06-15) He, Yuanmin; Liu, Hongliang; Luo, Sheng; Amos, Christopher I.; Lee, Jeffrey E.; Yang, Keming; Qureshi, Abrar A.; Han, Jiali; Wei, Qingyi; Epidemiology, School of Public HealthBoth in vivo and in vitro evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown. Methods: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients. Results: we identified two SNPs (EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, P=0.001) and 1.66 (1.22-2.26, P=0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets (P trend<0.001 and 0.002, respectively). Additional functional analysis revealed that both EML1 rs10151787 G and HIST1H4E rs2069018 C alleles were associated with elevated mRNA expression levels in normal tissues. Conclusions: Our findings suggest that EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS.Item Higher susceptibility to sunburn is associated with decreased plasma glutamine and increased plasma glutamate levels among US women: An analysis of the Nurses' Health Study I and II(Elsevier, 2021) Yang, Keming; Li, Xin; Zeleznik, Oana A.; Eliassen, A. Heather; Clish, Clary B.; Cho, Eunyoung; Somani, Ally-Khan B.; Qureshi, Abrar A.; Giovannucci, Edward L.; Nan, Hongmei; Epidemiology, School of Public HealthTo the Editor: The metabolism of glutamine and glutamate, 2 important amino acids synthesized in the human body, may have an etiologic role in melanoma, an aggressive skin malignancy. 1 , 2 Preclinical experiments and clinical trials have found that metabotropic glutamate receptor 1 blocker and glutamate release inhibitor (eg, Riluzole) can suppress melanoma cell migration, invasion, and proliferation. 2 Additionally, inhibiting glutaminase, the enzyme that converts glutamine to glutamate, further reduced glutamate bioavailability and suppressed tumor progression. 1 Susceptibility to sunburn, a pigmentary trait, is a well-known risk factor for melanoma. 3 However, it is unclear whether plasma glutamate and glutamine are affected by this host factor even before cancer onset.Item Indoor tanning use among white female students aged 18–30(Elsevier, 2017) Yang, Keming; Han, Jiali; Epidemiology, School of Public HealthItem Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults(Elsevier, 2020-08-01) Yang, Keming; Forman, Michele R.; Monahan, Patrick O.; Graham, Brett H.; Chan, Andrew T.; Zhang, Xuehong; De Vivo, Immaculata; Giovannucci, Edward L.; Tabung, Fred K.; Nan, Hongmei; Epidemiology, School of Public HealthBackground: Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives: Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods: This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results: We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.05 ± 0.05 (P-trend = 0.0004). Conclusions: Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.Item Meta‐analysis of the association between sodium‐glucose co‐transporter‐2 inhibitors and risk of skin cancer among patients with type 2 diabetes(Wiley, 2018) Tang, Huilin; Yang, Keming; Song, Yiqing; Han, Jiali; Epidemiology, School of Public HealthA slight increase in melanoma risk was observed among sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta‐analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT‐2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80‐5.89; I2, 0%). Similar results were observed in the subgroup analyses according to the type of SGLT‐2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non‐melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47‐1.07; I2, 0%), while a significantly decreased risk was observed among trials with duration <52 weeks (Peto OR, 0.12; 95% CI, 0.02‐0.59; I2, 0%). No evidence of publication bias was detected in the analyses. Current evidence from RCTs did not support a significantly increased risk of skin cancer associated with SGLT‐2 inhibitors.Item Mitochondrial DNA Copy Number, Insulinemic Potential of Lifestyle, and Colorectal Cancer(2020-03) Yang, Keming; Nan, Hongmei; Forman, Michele R.; Graham, Brett H.; Han, Jiali; Monahan, Patrick O.Because colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer death in the US, identifying biomarkers that might inform disease prevention and early diagnosis is of great public health importance. Mitochondria are key cytoplasmic organelles containing an independent genome, i.e., mitochondrial DNA (mtDNA). It has been increasingly recognized that mtDNA copy number (mtDNAcn) is a biomarker for mitochondrial function and cellular oxidative stress. To date, the few studies that have assessed associations between mtDNAcn and CRC outcomes have yielded inconsistent findings. Further, no epidemiologic study has examined the relationship between insulinemic potential of lifestyle and mtDNAcn. Therefore, in this dissertation, three studies were conducted using data from the Nurses’ Health Study and the Health Professionals Follow-Up Study. First, the association between pre-diagnostic leukocyte mtDNAcn and CRC risk was studied in a nested casecontrol study (324 cases/658 controls). Lower mtDNAcn was significantly associated with increased risk of CRC and proximal colon cancer. That inverse association remained significant among individuals with ≥ 8 years’ follow-up since blood collection, suggesting that mtDNAcn might serve as a long-term predictor of CRC risk. Second, possible associations of pre-diagnostic mtDNAcn with overall and CRC-specific survival were examined among 587 CRC patients. MtDNAcn was not significantly associated with survival overall or in subgroups by cancer location, grade, or stage. Among current smokers, there was an inverse association between one standard deviation (SD) decrease in mtDNAcn and increased overall death risk. Among patients diagnosed at or before 70.5 years of age and those with anti-inflammatory diets, reduced mtDNAcn was associated with lower CRC-specific death risk. Lastly, the cross-sectional association between empirical lifestyle index for hyperinsulinemia (ELIH) and mtDNAcn was investigated among 2,835 subjects without major chronic diseases (cancers, diabetes, and cardiovascular diseases). A significant inverse association was found: least-squares means ± SD of mtDNAcn z-score decreased dramatically across ELIH quintiles. Overall, the findings from this dissertation will contribute to the evaluation of mtDNAcn as a potential biomarker for CRC risk and prognosis, and inform future interventions designed to reduce the insulinemic potential of lifestyle factors to preserve mitochondrial function.