Browsing by Author "Zhang, Zhen"

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    Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy.
    (OncoTargets and therapy, 2015-01) Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen
    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.
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    Life expectancy and disparity: an international comparison of life table data.
    (BMJ Open, 2011-07-29) Vaupel, James W; Zhang, Zhen; van Raalte, Alyson A
    OBJECTIVES: To determine the contribution of progress in averting premature deaths to the increase in life expectancy and the decline in lifespan variation. DESIGN: International comparison of national life table data from the Human Mortality Database. SETTING: 40 developed countries and regions, 1840-2009. POPULATION: Men and women of all ages. MAIN OUTCOME MEASURE: We use two summary measures of mortality: life expectancy and life disparity. Life disparity is a measure of how much lifespans differ among individuals. We define a death as premature if postponing it to a later age would decrease life disparity. RESULTS: In 89 of the 170 years from 1840 to 2009, the country with the highest male life expectancy also had the lowest male life disparity. This was true in 86 years for female life expectancy and disparity. In all years, the top several life expectancy leaders were also the top life disparity leaders. Although only 38% of deaths were premature, fully 84% of the increase in life expectancy resulted from averting premature deaths. The reduction in life disparity resulted from reductions in early-life disparity, that is, disparity caused by premature deaths; late-life disparity levels remained roughly constant. CONCLUSIONS: The countries that have been the most successful in averting premature deaths have consistently been the life expectancy leaders. Greater longevity and greater equality of individuals' lifespans are not incompatible goals. Countries can achieve both by reducing premature deaths.
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    Losses of expected lifetime in the United States and other developed countries: methods and empirical analyses.
    (Demography, 2011-02) Shkolnikov, Vladimir M; Andreev, Evgeny M; Zhang, Zhen; Oeppen, James; Vaupel, James W
    Patterns of diversity in age at death are examined using e (†), a dispersion measure that equals the average expected lifetime lost at death. We apply two methods for decomposing differences in e (†). The first method estimates the contributions of average levels of mortality and mortality age structures. The second (and newly developed) method returns components produced by differences between age- and cause-specific mortality rates. The United States is close to England and Wales in mean life expectancy but has higher life expectancy losses and lacks mortality compression. The difference is determined by mortality age structures, whereas the role of mortality levels is minor. This is related to excess mortality at ages under 65 from various causes in the United States. Regression on 17 country-series suggests that e (†) correlates with income inequality across countries but not across time. This result can be attributed to dissimilarity between the age- and cause-of-death structures of temporal mortality reduction and intercountry mortality variation. It also suggests that factors affecting overall mortality decrease differ from those responsible for excess lifetime losses in the United States compared with other countries. The latter can be related to weaknesses of health system and other factors resulting in premature death from heart diseases, amenable causes, accidents and violence.
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    Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma (ESCC) in Eastern Chinese populations.
    (PloS one, 2012-01) Zhu, Mei-Ling; Shi, Ting-Yan; Hu, Hai-Chuan; He, Jing; Wang, Mengyun; Jin, Li; Yang, Ya-Jun; Wang, Jiu-Cun; Sun, Meng-Hong; Chen, Huan; Zhao, Kuai-Le; Zhang, Zhen; Chen, Hai-Quan; Xiang, Jia-Qing; Wei, Qing-Yi
    BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies.
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    TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy.
    (Medicine, 2015-11) Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen
    Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings.