Entity

Time filter

Source Type


Sun Y.,Peking Union Medical College | Shi N.,Peking Union Medical College | Lu H.,Peking Union Medical College | Zhang J.,Peking Union Medical College | And 9 more authors.
Carcinogenesis | Year: 2014

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cause of cancer-related death worldwide. However, previous genome-wide single nucleotide polymorphism association analyses have not explained the high heritability associated with ESCC. In this study, we performed genome-wide copy number variation (CNV) analysis on 128 discordant sibling pairs to identify novel genes that contribute to ESCC susceptibility. A total of 57 774 individual CNVs were identified, and an interactive network of common CNVassociated genes was constructed, which showed that several ABC transporter genes contain CNVs in ESCC patients. Independent validation of a CNV at 13q32.1 in 1048 northern Chinese Han subjects demonstrated that the amplification of ABCC4 significantly correlated with ESCC risk [odds ratio: 3.36 (1.65-7.93), P = 0.0013]. Immunohistochemistry staining suggested that high copy numbers correlated with increased protein levels. High expression of ABCC4 was an independent poor prognostic factor for ESCC [relative risk: 1.73 (1.10-2.73), P = 0.0181]. The CNV region showed strong enhancer activity. Furthermore, inhibition of ABCC4 protein in ESCC cells decreased cell proliferation and motility via the inhibition of COX-2, PGE2 receptors and c-Myc expression; AKT, extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation; and β-catenin nuclear translocation in ESCC cells. In conclusion, the CNV at 13q32.1 is associated with ESCC susceptibility, and a gene within this locus, ABCC4, activates the oncogenic pathways in ESCC and thus facilitates cancer cell development and progression. A direct genetic contribution of ESCC risk through CNV common variants was determined in this study, and ABCC4 might therefore have predictive and therapeutic potential for ESCC. © The Author 2014.Published by Oxford University Press. All rights reserved. Source


Sun Y.-L.,Peking Union Medical College | Zhang J.-Q.,Peking Union Medical College | Mao Y.-H.,Yangquan Cancer Prevention and Treatment Institute | Han L.-F.,Yangquan Cancer Prevention and Treatment Institute | And 6 more authors.
World Chinese Journal of Digestology | Year: 2010

AIM: To explore the main environmental risk factors for esophageal squamous cell carcinoma (ESCC) based on discordant sib pairs (DSPs) in a moderately high-incidence area, Yangquan City, Shanxi Province, and to provide theoretical evidence for developing effective control and prevention measures in this area. METHODS: A 1:1 matched case-control study was carried out. One hundred and twenty-seven DSPs were recruited from the cancer registration and follow-up system of the local hospital. All ESCC cases and their matched unaffected sibs were subjected to a survey to obtain demographic information along with personal and family history, and lifestyle factors. The McNemar test was used for data analysis. RESULTS: Compared with matched unaffected sibs, low family income (OR = 2.00, 95% CI: 1.14-3.52, P = 0.0143), hot food eating and drinking (OR = 2.56, 95% CI: 1.44-4.57, P = 0.0009) and heavy drinking (P = 0.0027) were risk factors for ESCC in the area. These factors play important roles in the development of ESCC, even in cases with a family history of ESCC, and the odds ratios (95% CI) were 2.18 (1.07-4.45), 5.00(1.91-13.06) and infinity, respectively. CONCLUSION: Besides genetic factors, lack of nutrition, hot food eating and heavy drinking are main risk factors for ESCC in Yangquan City. Prevention and control of ESCC should be intervened at multiple levels, such as genetic factors and lifestyles. Source

Discover hidden collaborations