Browsing by Author "Sun, Yan"

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    A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
    (International journal of cancer, 2018-09) Tao, Ye; Sturgis, Erich M; Huang, Zhigang; Sun, Yan; Dahlstrom, Kristina R; Wei, Qingyi; Li, Guojun
    TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility. HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma (OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic white population, and used logistic regression models to evaluate the joint effects on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6-960.4) or never-drinkers (OR, 196.0; 95% CI, 28.2-1,000.0), respectively. Younger subjects had a higher risk of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3-87.0 vs. OR, 6.0; 95% CI, 1.7-17.9, respectively). The significant associations between this polymorphism and HPV16-associated OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results. Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects who are never-smokers, never-drinkers and young. This result may help us understand the tumorigenesis process and improve early detection, which are critical for prevention and intervention strategies. However, larger studies are needed to validate our findings.
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    Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
    (Int J Cancer, 2015-11-15) Zhang, Fenghua; Sturgis, Erich M; Sun, Yan; Zhang, Yang; Wei, Qingyi; Zhang, Caiyun; Zheng, Hongliang; Li, Guojun
    Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.
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    Lymphocyte Telomere Length Predicts Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.
    (Carcinogenesis, 2019-02-05) Luo, Xiaoning; Sturgis, Erich M; Yang, Zheng; Sun, Yan; Wei, Peng; Liu, Zhensheng; Wei, Qingyi; Li, Guojun
    Since lymphocyte telomere length (LTL) plays critical roles in the maintenance of genomic stability and integrity, LTL thus may influence the etiology and prognosis of squamous cell carcinoma of the oropharynx (SCCOP). However, given the association between LTL and risk of HPV-associated SCCOP and between LTL and tumor HPV status of SCCOP, we hypothesized that LTL is associated with SCCOP prognosis, particularly in HPV-positive patients after definitive radiotherapy. LTL and tumor HPV type 16 (HPV16) status were determined in 564 incident SCCOP patients before radiotherapy or chemoradiation. Both univariate and multivariable Cox regression analyses were performed to estimate the association between LTL and prognosis. Eighty-five percent of the patients had HPV16-positive tumors. Patients with shorter telomeres had significantly better overall, disease-specific, and disease-free survival than did those with longer telomeres (log-rank p < 0.001). Moreover, patients with shorter telomeres had significantly lower risk of death overall (hazard ratio [HR], 0.2; 95% confidence interval [CI], 0.1-0.4), death due to SCCOP (HR, 0.2; 95% CI, 0.1-0.4), and SCCOP recurrence (HR, 0.3; 95% CI, 0.2-0.5) after adjusting for other important prognostic confounders. Finally, we found more pronounced effects of LTL on survival in HPV16-positive SCCOP patients after stratified analysis according to tumor HPV status. These findings indicate that LTL plays a significant role in the survival of patients with SCCOP, especially HPV16-positive patients who undergo definitive radiotherapy. Therefore, pretreatment LTL may be an independent prognostic biomarker for HPV16-positive SCCOP. Prospective studies with larger sample sizes are needed to confirm these findings.
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    Perception of Stigma and Its Associated Factors Among Patients With Major Depressive Disorder: A Multicenter Survey From an Asian Population.
    (Frontiers in psychiatry, 2019-01) Sun, Yan; Chen, Gang; Wang, Li; Li, Nan; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chen, Chia-Hui; Udomratn, Pichet; Bae, Jae Nam; Fang, Yi-Ru; Chua, Hong Choon; Liu, Shen-Ing; George, Tom; Bautista, Dianne; Chan, Edwin; Rush, A John; Yang, Hong; Su, Yun-Ai; Si, Tian-Mei
    Stigma of major depressive disorder (MDD) is an important public health problem. This study aimed to examine the level of perceived stigma and its associated factors in MDD patients in five Asian countries, including China, Korea, Malaysia, Singapore, and Thailand. A total of 547 outpatients with MDD were included from Asian countries. We used the stigma scale of the Explanatory Model Interview Catalogue (EMIC) to assess stigma. The Montgomery-Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R), Fatigue Severity Scale (FSS), Sheehan Disability Scale (SDS), 36-Item Short-Form Health Survey (SF-36), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess symptoms, clinical features, functional impairment, health status, and social support. The stigma scores of patients under 55 years old were significantly higher than those equal to or greater than 55 years old (P < 0.001). The stigma scores exhibited significant negative correlation with age; MSPSS scores of family, friends, and others; and SF-36 subscale of mental health, but significant positive correlation with MADRS, FSS, SDS, and SCL-90-R subscale scores of depression, interpersonal sensitivity, obsession-compulsion, psychoticism, and somatization. Multivariate regression analysis revealed that age, SCL-90-R interpersonal sensitivity, obsession-compulsion, psychoticism, MSPSS scores of friends and others, and SF-36 of mental health were significantly associated with the level of perceived stigma. These findings suggest that MDD patients who are young, have a high degree of interpersonal sensitivity and psychoticism, have low health-related quality of life, and have low social support are the target population for stigma interventions in Asia.
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    Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck.
    (BMC cancer, 2016-02-08) Sun, Yan; Yu, Wenbin; Sturgis, Erich M; Peng, Wei; Lei, Dapeng; Wei, Qingyi; Song, Xicheng; Li, Guojun
    FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.
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    The Effects of Negative Ion Indoor Air Filtration on Selected Biomarkers in Healthy Adults: A Randomized Double-Blind Crossover Trial
    (2020-04-24) Sun, Yan
    Air pollution is a significant challenge in environmental health. According to the World Health Organization (WHO), about 91% of world’s population live in areas where WHO’s air quality guidelines were not met. Ambient air pollution causes approximately 4.2 million premature deaths worldwide. While outdoor ambient air quality is associated with global mortality, indoor air pollution also possesses a significant challenge to people’s health and well-being. In countries with less desirable air quality, the use of air filtration devices is common. Despite the rise of negative ion air filtration device usage, the purification efficiency and health effects of these devices remain unclear. The goal of this project is to evaluate health impacts of indoor negative ion air filtration intervention in healthy young adults. The intervention is hypothesized to reduce indoor fine particulate matter exposure and reduce adverse health effects associated with indoor PM2.5 pollution. We conducted a randomized, double-blind, cross-over study with two specific aims: first, to evaluate the effectiveness of PM2.5 removal by negative ion air filtration device; second, to evaluate differences in health endpoints associated with PM2.5 exposure between the two interventions. Fifty-five healthy adults participated in this study. Each participant received a random sequence of true and sham filtration intervention, with two weeks of washout period in between. Before and after each intervention period, these participants provided biological samples so we could measure specific biomarkers of interest to assess health impacts of each intervention. My project only assessed urinary biomarkers. Overall, only one out of the five biomarkers selected has statistically significant result. No significant difference between true and sham intervention is observed for urinary fMDA and (biomarkers of lipid peroxidation, reflecting cell membrane damage), 8-OHdG (a biomarker of oxidative damage to DNA), and 11-OHTXB1 (a biomarker of platelet activation, reflecting thrombosis risk). The findings indicate that the negative ion filtration did not lead to significant changes in biomarkers expected to be associated with fine particle exposure reduction. More research is needed to investigate other health endpoints and long-term changes associated with the use of negative ion air filtration device.