National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.

ObjectivesTo estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China.DesignThis multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group.ResultsOur cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively.ConclusionAmong individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study including 1,053 incident gastric cancer patients and 1,100 cancer-free controls in a high-risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR 51.37, 95% CI 5 1.15-1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal-type gastric cancer (p 5 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR 5 1.14, 95% CI 5 0.96-1.36). A small meta-analysis including 5 case-control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR 5 1.83, 95% CI: 1.29-2.60 and OR 5 1.84, 95% CI: 1.33-2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.Approximately 40% gastric cancer cases occur in China, 1 which remains a huge burden for Chinese and is one of the key public health issues in cancer prevention and control for Chinese government. Gastric cancer, predominantly adenocarcinoma, could be further classified as intestinal and diffuse subtypes.2 Intestinal-type tumors are characterized by a corpus-dominated gastritis with gastric atrophy and intestinal metaplasia, whereas diffuse-type tumors are characterized by gastritis throughout the stomach.3 Intestinal-type tumors are found predominantly in geographic areas with a high incidence of gastric cancer, whereas diffuse-type tumors are found more uniformly throughout the world.The exact mechanism of gastric cancer development remains unclear. Although some exogenous factors, such as diet, tobacco smoke and Helicobacter pylori, have been proposed to play important role in gastric carcinogenesis, the genetic susceptibility factors may also contributed to gastric cancer development, especially to diffuse-type gastric cancer. 4,5 The prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein, which is a cell surface antigen. PSCA is highly expressed by a large proportion of human prostate tumors, incl...

To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiologic study in China. One hundred and twentyfive histologically confirmed ESCC patients having undergone surgery in the Yangzhong People's Hospital between January 2005 and March 2006 were recruited. The aberrant CpG island hypermethylation of P16, MGMT, and hMLH1 genes could be found in cancer tissues with frequency of about 88.0%, 27.2%, and 3.2%, respectively, and in remote normal-appearing esophageal tissues with frequency of about 36.8%, 11.2%, and 0.0%, respectively. No hypermethylation was found in the normal esophageal tissues from healthy controls. Compared with those patients without lymph node metastasis, MGMT gene showed a higher proportion of hypermethylation in cancer tissues, whereas P16 gene showed a higher proportion of hypermethylation in remote normal-appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues, with odds ratio of 3.34 (95% confidence interval, 1.07-10.39) and 3.83 (95% confidence interval, 1.13-12.94), respectively. This study indicated that the aberrant CpG island hypermethylation of cancerrelated genes was associated with ESCC and might be a promising biomarker in diagnosis and prognosis.

Growing evidence suggests that the transforming growth factor b (TGF-b) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGFb1 and its receptor TGF-bRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastric cancer [adjusted odds ratio (OR) 5 0.65, 95% confidence interval (CI) 5 0.52-0.82 for 2509CT/TT and adjusted OR 5 0.67, 95% CI 5 0.53-0.85 for 2875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR 5 0.44, 95% CI 5 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. ' 2006 Wiley-Liss, Inc.

ObjectiveThis study aims to describe the findings from a massive endoscopic screening program in a high-risk area of China and to evaluate the prognosis of patients diagnosed through endoscopic screening compared with those diagnosed at usual hospital visits because of illness.MethodsIn 2006, an early detection and treatment program was initiated in Yangzhong county, China. Local residents aged 40–69 years were eligible for free endoscopic screening. Endoscopic examination was performed with Lugol’s iodine staining, followed by biopsies. Patients diagnosed with esophageal or gastric cancer were referred for treatment and followed to assess their long-term survival status.ResultsFrom 2006 through 2012, we screened 12453 participants, including 5334 (42.8%) men and 7119 (57.2%) women. The average age was 52.8±8.0 years. We detected 166 patients with upper digestive tract cancers, including 106 cancers in the esophagus (detection rate: 0.85%) and 60 cancers in the stomach (detection rate: 0.48%). Of these patients, 98.11% with esophageal cancer and 100% with gastric cancer were defined as at the early stage. In the process of follow-up, 17 patients died from cancer-related causes, and the median survival time was greater than 85 months. The overall survival rates for 1, 3 and 5 years were 98.0%, 90.0% and 89.0%, respectively. A significant positive effect was observed for the long-term survival of patients diagnosed through massive endoscopic screening.ConclusionsIn a high-risk population, massive endoscopic screening can identify early stage carcinoma of esophageal and gastric cancers and improve patients’ prognosis through early detection and treatment.

Purpose: Accumulative evidence suggests that folate has a protective effect on gastric cancer.The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase (MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results: The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for 401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TTgenotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls (P < 0.01), and the upper quartile of tHcy (>13.6 Amol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy (V8.0 Amol/L; adjusted OR, 1.82; 95% CI, 1.20-2.75). Conclusions: The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.

In contrast to children and adults with TOF/APV, neonates and small infants presenting with respiratory symptoms require prolonged ventilation and additional reinterventions for airway compression. Our current surgical approach which includes reduction and suspension of pulmonary arteries, reconstruction of a competent RVOT, and aggressive postoperative ventilatory management to relieve airway obstruction offers satisfactory outcomes.