Gansu Provincial Academy of Medical science

Lanzhou, China

Gansu Provincial Academy of Medical science

Lanzhou, China
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Chen Y.,Lanzhou University | Chen Y.,Yale University | Zheng T.,Yale University | Lan Q.,U.S. National Cancer Institute | And 11 more authors.
Blood | Year: 2011

We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 P forinteraction = .016) for NHL overall; IL7R (rs1494555 P forinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P forinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P forinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.


Kim C.,Yale University | Zheng T.,Yale University | Lan Q.,U.S. National Cancer Institute | Chen Y.,Yale University | And 9 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012

Background: Being overweight and obese increases oxidative stress in the body. To test the hypothesis that genetic variations in oxidative stress pathway genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL), we conducted a population-based case-control study in Connecticut women. Methods: Individuals who were overweight/obese (BMI ≥ 25) were compared with normal and underweight individuals (BMI < 25), and their risk of NHL stratified assuming a dominant allele model for each oxidative stress pathway single-nucleotide polymorphism. Results: Polymorphisms in AKR1A1, AKR1C1, AKR1C3, CYBA, GPX1, MPO, NCF2, NCF4, NOS1, NOS2A NOS3, OGG1, ATG9B, SOD1, SOD2, SOD3, RAC1, and RAC2 genes after false discovery rate adjustment did not modify the association between BMI and risk of NHL overall and histologic subtypes. Conclusions: The results suggest that common genetic variations in oxidative stress genes do not modify the relationship between BMI and risk of NHL. Impact: Studies of BMI and oxidative stress independently may elevate NHL risk, but this study suggests no interaction of the two risk factors. Future studies with larger study populations may reveal interactions. ©2012 AACR.


Lu L.,Yale Cancer Center | Zhu G.,Yale Cancer Center | Zhu G.,Gansu Provincial Academy of Medical Science | Zhang C.,Yale Cancer Center | And 12 more authors.
Breast Cancer Research and Treatment | Year: 2012

Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12, interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene activities. Recent work suggests that it may have effects on breast cancer progression and survival. We evaluated HOTAIR expression and the methylation status of its downstream intergenic CpG island in primary breast cancers, and examined associations of these factors with clinical and pathologic features and patient survival. HOTAIR expression and DNA methylation were analyzed in tissue from 348 primary breast cancers with quantitative RT-PCR and methylation-specific PCR, respectively. HOTAIR expression and methylation varied widely in the tissues. A positive correlation was found between DNA methylation and HOTAIR expression. Methylation was associated with unfavorable disease characteristics, whereas no significant associations were found between HOTAIR expression and clinical or pathologic features. In multivariate, but not in univariate, Cox proportional hazard regression models, patients with high HOTAIR expression had lower risks of relapse and mortality than those with low HOTAIR expression. These findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies. © 2012 Springer Science+Business Media New York.


Lu L.,Yale University | Zhang C.,Yale University | Zhang C.,Gansu Provincial Hospital for the Protection of Mother and Babys Health | Zhu G.,Yale University | And 7 more authors.
Breast Cancer Research | Year: 2011

Introduction: Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis.Methods: qPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality.Results: Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy.Conclusions: Overall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy. © 2011 Lu et al.; licensee BioMed Central Ltd.


Zhu G.,Lanzhou University | Zhu G.,Gansu Provincial Academy of Medical science | Su H.,Gansu Provincial Academy of Medical science | Lu L.,Yale University | And 7 more authors.
Oncotarget | Year: 2016

Background: Balance of DNA damage and proper repair plays an important role in progression of bladder cancer. Here we aimed to assess the associations of nineteen polymorphisms from seven DNA repair-associated genes (PRAP1, OGG1, APEX1, MUTYH, XRCC1, XRCC2 and XRCC3) with bladder cancer and their interactions in the disease in a Han Chinese population. Methodology/Principal Findings: A chip-based TaqMan genotyping for the candidate genes was performed on 227 bladder cancer patients and 260 healthy controls. APEX1 rs3136817, MUTYH rs3219493, three SNPs (rs3213356, rs25487 and rs1799782) in XRCC1, and three SNPs (rs1799794, rs861531 and rs861530) in XRCC3 showed significant associations with the risk of bladder cancer. In haplotype analysis, elevated risks of bladder cancer were observed in those with either haplotype GT (OR = 1.56, P = 0.003) of APEX1, or GGGTC (OR = 2.05, P = 0.002) of XRCC1, whereas decreased risks were in individuals with either GCGCC (OR = 0.40, P = 0.001), or GCGTT (OR=0.60, = 0.005) of XRCC1, or CCC (OR = 0.65, P = 0.004) of MUTYH, or TTTAT (OR = 0.36, P = 0.009) of XRCC3. Interaction analysis showed that the two-loci model (rs1799794 and rs861530) was the best with the maximal testing accuracy of 0.701, and the maximal 100% cross-validation consistency (P = 0.001). Conclusions: Polymorphisms and haplotypes of DNA repair genes are associated with the risk of bladder cancer, and of which the SNPs (rs1799794 and rs861530) in XRCC3 gene might be two major loci in relation to the susceptibility to bladder cancer in a northwest Chinese population.


PubMed | Gansu Provincial Academy of Medical science, Lanzhou University and Key Laboratory of TCM Pharmacology and Toxicology of Gansu Province
Type: | Journal: BMC complementary and alternative medicine | Year: 2016

Cedrus deodara is one of the traditional Chinese medicinal herbs that exhibits a line of biological activities. The current study extracted the total flavonoids from the pine needles of Cedrus deodara (TFPNCD), and investigated its anti-cancer effects in tumor cell lines.The total flavonoids was extracted from pine needles of Cedrus deodara by ethanol hot refluxing and purified by HPD722 macroporous resin. The contents of total flavonoids and the active ingredients of TFPNCD were analyzed through UV and HPLC. MTT assay was used to investigate its inhibitory effect on tumor cell lines. The flow cytometry was employed to determine the apoptosis and cell cycle distribution after treated TFPNCD on HepG2 cells.The TFPNCD, in which the contents of total flavonoid reached up to 54.28 %, and the major ingredients of myricetin, quercetin, kaempferol and isorhamnetin in TFPNCD were 1.89, 2.01, 2.94 and 1.22 mg/g, respectively. The MTT assays demonstrated that TFPNCD inhibited the growth of HepG2 cells in a dose-dependent manner, with the IC50values of 114.12 g/mL. By comparison, TFPNCD inhibited the proliferation to a less extent in human cervical carcinoma HeLa, gastric cancer MKN28 cells, glioma SHG-44 cells and lung carcinoma A549 than HepG2 cells. We found that even at the lower doses, the total flavonoids effectively inhibited the proliferation of HepG2 cells. Comparison of IC50 values implicated that HepG2 cells might be more sensitive to the treatment with total flavonoids. TFPNCD was able to increase the population of HepG2 cells in G0 /G1 phase. Meanwhile, TFPNCD treatment increased the percentage of apoptotic HepG2 cells.These data suggested that TFPNCD might have therapeutic potential in cancer through the regulation of cell cycle and apoptosis.


PubMed | Xigu District of Lanzhou City Peoples Hospital, Gansu Provincial Academy of Medical science, Lanzhou University and Yale University
Type: Journal Article | Journal: Oncotarget | Year: 2016

Balance of DNA damage and proper repair plays an important role in progression of bladder cancer. Here we aimed to assess the associations of nineteen polymorphisms from seven DNA repair-associated genes (PRAP1, OGG1, APEX1, MUTYH, XRCC1, XRCC2 and XRCC3) with bladder cancer and their interactions in the disease in a Han Chinese population.A chip-based TaqMan genotyping for the candidate genes was performed on 227 bladder cancer patients and 260 healthy controls. APEX1 rs3136817, MUTYH rs3219493, three SNPs (rs3213356, rs25487 and rs1799782) in XRCC1, and three SNPs (rs1799794, rs861531 and rs861530) in XRCC3 showed significant associations with the risk of bladder cancer. In haplotype analysis, elevated risks of bladder cancer were observed in those with either haplotype GT (OR = 1.56, P = 0.003) of APEX1, or GGGTC (OR = 2.05, P = 0.002) of XRCC1, whereas decreased risks were in individuals with either GCGCC (OR = 0.40, P = 0.001), or GCGTT (OR = 0.60, = 0.005) of XRCC1, or CCC (OR = 0.65, P = 0.004) of MUTYH, or TTTAT (OR = 0.36, P = 0.009) of XRCC3. Interaction analysis showed that the two-loci model (rs1799794 and rs861530) was the best with the maximal testing accuracy of 0.701, and the maximal 100% cross-validation consistency (P = 0.001).Polymorphisms and haplotypes of DNA repair genes are associated with the risk of bladder cancer, and of which the SNPs (rs1799794 and rs861530) in XRCC3 gene might be two major loci in relation to the susceptibility to bladder cancer in a northwest Chinese population.


Kim C.,Yale University | Bi X.,Yale University | Bi X.,Chinese Academy of Sciences | Pan D.,Yale University | And 7 more authors.
Thyroid | Year: 2013

Background: Thyroid cancers have increased dramatically over the past few decades. Comorbidities may be important, and previous studies have indicated elevated second cancer risk after initial primary thyroid cancers. This study examined the risk of second cancers after development of a thyroid cancer, primary utilizing the Surveillance, Epidemiology, and End Results (SEER) program database. Methods: The cohort consisted of men and women diagnosed with first primary thyroid cancer who were reported to a SEER database in 1973-2008 (n=52,103). Standardized incidence ratios (SIR) were calculated for all secondary cancers. Confidence intervals and p-values are at 0.05 significance alpha level and are two-sided based on Poisson exact methods. Results: In this cohort, 4457 individuals developed second cancers. The risk of developing second cancers after a primary thyroid cancer varied from 10% to 150% depending on different cancer types. Cancers in all sites, breast, skin, prostate, kidney, brain, salivary gland, second thyroid, lymphoma, myeloma, and leukemia were elevated. The magnitude of the risk varied by histology, tumor size, calendar year of first primary thyroid cancer diagnosis, and the treatment of the primary thyroid cancer. The risk of a second cancer was elevated in patients whose first primary thyroid carcinomas were small, or were diagnosed after 1994, or in whom some form of radiation treatment was administered. Conclusions: This large population-based analysis of second cancers among thyroid cancer patients suggests that there was an increase of second cancers in all sites, and the most commonly elevated second cancers were the salivary gland and kidney. Additionally, the increase in second cancers in patients with recently diagnosed thyroid microcarcinomas (<10 mm) suggests that aggressive radiation treatment of the first primary thyroid cancer, the environment, and genetic susceptibility, may increase the risk of a second cancer. © 2013, Mary Ann Liebert, Inc.


PubMed | Gansu Provincial Academy of Medical science
Type: Journal Article | Journal: Frontiers in oncology | Year: 2012

We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR = 0.5, 95%CI: 0.3-0.9), IL13 (rs20541) GG genotype (OR = 0.6, 95%CI: 0.4-0.9), and IL13 (rs1295686) CC genotype (OR = 0.6, 95%CI: 0.4-0.8), but not among women who carried IFNGR2 CC, IL13 AG/AA, and IL13CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 P(for interaction) = 0.024), IL13(rs20541 P(for interaction) = 0.005), IL13 (rs1295686 P(for interaction) = 0.008), and IL15RA (rs2296135 P(for interaction) = 0.049) for NHL overall; IL13 (rs20541 P(for interaction) = 0.0009), IL13(rs1295686 P(for interaction) = 0.0002), and IL15RA (rs2296135 P(for interaction) = 0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between HRT and NHL risk.


PubMed | Gansu Provincial Academy of Medical science
Type: Journal Article | Journal: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus | Year: 2012

The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted.

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