Common genetic variants in the 9p21 region and their associations with multiple tumours

Background:

The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers.

Methods:

We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9–32.8 Mb) in eight case–control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction.

Results:

Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10⁻⁶). The CDKN2A-ESCC association was further supported by gene-based analyses (P_gene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10⁻⁴). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007).

Conclusion:

Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.     

2014年山西省肿瘤登记地区恶性肿瘤发病与死亡分析

目的探讨2014年山西省肿瘤登记地区恶性肿瘤发病与死亡情况。方法收集2014年全省12个肿瘤登记地区的数据资料,分析不同地区、不同年龄和性别的恶性肿瘤发病率与死亡率特点,同时与全国数据进行比较。结果2014年山西省肿瘤登记地区新发恶性肿瘤11703例(男性6559例,女性5144例),发病率为221.21/10万,中国人口标化发病率为163.91/10万,世界人口标化发病率为163.25/10万;城市地区发病率、中国人口标化发病率分别为247.02/10万、171.35/10万,农村地区分别为205.98/10万、159.03/10万。男性常见恶性肿瘤发病以胃癌、肺癌、食管癌、肝癌、结直肠癌为主,女性以乳腺癌、子宫颈癌、肺癌、食管癌、胃癌为主。恶性肿瘤死亡病例7283例(男性4548例,女性2735例),恶性肿瘤死亡率为137.66/10万,中国人口标化死亡率为99.67/10万,世界人口标化死亡率为100.11/10万;城市地区死亡率、中国人口标化死亡率分别为141.03/10万、92.84/10万,农村地区分别为135.68/10万、103.69/10万。男性常见恶性肿瘤死亡以肺癌、胃癌、肝癌、食管癌、结直肠癌为主,女性以肺癌、胃癌、肝癌、食管癌、子宫颈癌为主。结论山西省肿瘤登记地区恶性肿瘤发病与死亡均以肺癌、上消化道恶性肿瘤和女性子宫颈癌为主,胃癌、子宫颈癌的发病率较高。     

苏木精对人类膀胱癌T24细胞的杀伤及诱导凋亡作用

目的观察苏木精对人类膀胱癌T24细胞的杀伤及诱导凋亡的作用，探讨其对靶细胞杀伤的作用机制。方法将靶细胞培养于含药量分别为0、12．5、25、50、100、200μg／ml的RPMI1640培养基中，培养24h，倒置显微镜下观察细胞的形态学变化，收集靶细胞，采用锥虫蓝拒染法测定药物对靶细胞的杀伤作用。采用流式细胞术（FCM）检测不同药物质量浓度对靶细胞凋亡的影响。结果随着药物质量浓度的逐步增加，细胞发生形态学变化，且细胞死亡率逐步增加，对照组细胞死亡率为（2．63±0．29）％，各组细胞死亡率分别为（10．00±4．82）％、（21．88±3．42）％、（76．41±4．82）％、（92．27±7．62）％和（96．34±8．78）％。对照组细胞凋亡的自然发生率为0．47％；含药量为50μg／ml时，细胞凋亡率显著增高，达到43．18％，死细胞率为48．47％，活细胞率为8.35％；随着药物质量浓度的增大，细胞凋亡率逐渐降低。而死细胞率则逐渐上升。结论苏木精可通过诱导细胞凋亡和直接杀伤作用于靶细胞，在较低浓度下，可诱导靶细胞发生凋亡，药物浓度超过100μg／ml时，则能直接杀死靶细胞。     

Expression of Neuropeptide Y in Human Pituitary Adenoma

OBJECTIVE Neurppeptide Y (NPY) acts as a neuroendocrine modulator in the anterior pituitary, and NPY mRNA and NPY-immunoreactivity have been detected in normal human anterior pituitaries. However, only a few studies of NPY expression in human pituitary adenomas have been published. Our study was conducted to determine whether or not adenoma-tous cells express NPY, to investigate the relationship between NPY expression and the subtypes of pituitary adenoma and to explore the clinical significance of NPY. METHODS The study included tissues from 58 patients with pituitary adenomas who underwent surgery because of their clinical diagnosis. Using a highly specific anti-NPY polyclonal antibody, immunohistochemi-cal analysis was performed on the surgically removed pituitary adenomas. Six fresh specimens also were examined using immuno-electron microscopy. NPY was labeled with colloidal gold in order to study the distribution of NPY at the subcellular level. RESULTS The NPY expression level was significantly different among subgroups of pituitary adenomas (P<0.05). NPY was immuno-detected in 58.6% of all adenomas, in 91.7% of gonadotrophic adenomas and in 14.3% of prolactinomas. NPY expression was slightly lower in invasive pituitary adenomas compared to noninvasive adenomas, but the difference was not significant (t=1.81, P>0.05). Of particular interest was the finding that vascular endothelial cells showed positive NPY expression in some pituitary adenomas. Parts of strongly positive tumor cells were seen in channels formed without endothelial cells, but which contained some red blood cells in a formation similar to so-called vasculogenic mimicry. Im-muno-electron microscopy demonstrated that 4 of the 6 fresh specimens displayed positive NPY staining with a high density of gold particles located mainly in the secretory granulas. In addition, gold particles were sparsely detected in the rough endoplasmic reticulum and cell matrix. CONCLUSION NPY exists in pituitary adenomas and its expression level was related to the types and biological characteristics of the pituitary adenomas. NPY may have a depressive effect on tumor cellular proliferation in pituitary adenomas. NPY possibly participates in modulating an-giogenesis and hemodynamic changes in pituitary adenomas.     

Influence of Age and Histology on Outcome in Adult Non-Hodgkin Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation (HCT): A Report from The Center For International Blood & Marrow Transplant Research (CIBMTR)

To compare the clinical outcomes of older (age ≥55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged ≥55 years to 1949 NHL patients <55 years during the years 1990–2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended.     

Chromosomal fragile sites to lymphoma with observation of 40 patients

Chromosomal fragile sites studies were performed in 40 patients with lymphoma and 30 individuals as healthy controls. The results showed that there was a statistical difference of chromosomal aberration between the two groups; The patients carried 46 fragile sites totally; 21 out of 46 fragile sites in lymphoma corresponded with cancer breakpoints, and 9 fragile sites were located in the bands where concogenes exist. These suggest a certain association between fragile sites, cancer breakpoints and oncogenes and thus indicate a possible important role of fragile sites in the pathogenesis of lymphoma.     

肝癌射频消融后肝脓肿的发生率及危险因素分析

目的探讨肝癌射频消融(RFA)后肝脓肿形成的发生率及危险因素。方法回顾性分析2000年1月—2016年6月接受RFA治疗的1 643例肝癌患者的资料,包括原发性肝细胞癌(HCC)942例、胆管细胞癌(CCC)31例、转移性肝癌(MLC)670例,采用Logistic回归对影响因素进行分析。结果肝癌RFA治疗后肝脓肿发生率为0.79%(13/1 643)。单因素分析显示,糖尿病史、肝功能Child-Pugh分级、手术史及肿瘤位置与肝癌RFA治疗后肝脓肿形成相关(P均0.05);多因素分析显示,糖尿病史、手术史及肿瘤位置为肝癌RFA治疗后肝脓肿形成的独立危险因素。结论糖尿病史、手术史、肿瘤位置是影响肝癌RFA治疗后肝脓肿形成的重要因素。     

Silencing LINC01234 represses pancreatic cancer progression by inhibiting the malignant phenotypes of pancreatic cancer cells

ObjectivePrevious works have outlined the pivotal involvement of long intergenic non-coding RNA (lincRNA) in cancer progression, while the efficiency of LINC01234 in pancreatic cancer remained obscure. The purpose of this research is to unravel the regulatory mechanism of LINC01234 in pancreatic cancer via modulating microRNA (miR)-513a-3p and hexose 6-phosphate dehydrogenase (H6PD).MethodsPancreatic cancer cells were cultured and clinical tissue specimens were collected. LINC01234, miR-513a-3p and H6PD levels in pancreatic cancer cells and tissues were examined. Plasmids altering LINC01234, miR-513a-3p and H6PD expression were transfected into pancreatic cancer cells to assess the change in biological behaviors of pancreatic cancer cells. The targeting relations among LINC01234, miR-513a-3p and H6PD were validated.ResultsLINC01234 and H6PD levels were elevated while miR-513a-3p level was reduced in pancreatic cancer cells and tissues. LINC01234 deficiency hindered the malignant biological activities of pancreatic cancer cells. MiR-513a-3p depletion or H6PD elevation could abrogate the inhibitory effects of LINC01234 silencing on pancreatic cancer cells. LINC01234 sponged miR-513a-3p that targeted H6PD.ConclusionThe reduced LINC01234 exerts inhibitory impacts on pancreatic cancer cells via targeting miR-513a-3p to restrain H6PD level. The current study broadens the understanding of LINC01234 function and affords novel therapeutic targets for pancreatic cancer treatment.