BackgroundFamily history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse.Methods600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated.ResultsIncreased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29).ConclusionThese data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.

ObjectiveTo profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy.MethodsWe performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62) and gastric noncardia adenocarcinomas (n = 72) and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases.ResultsPrincipal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude) in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47%) dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%), and about one-fourth in noncardia only (n = 144, 28%). Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers.ConclusionsThe dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.

Dietary, smoking, and drinking habits, as well as sociopsychological factors and familial history, were investigated in a case-control study on the etiology of esophageal cancer (EC) in two areas of Shanxi (Yangcheng and Linfen), north central China. Data were analyzed from 326 cases and 396 controls. We identified several factors associated with high or low risk; some were common across the areas and others were area-specific. Consumption of millet gruel was associated positively with EC, in a dose-response relationship. An increase in EC risk was seen for consumption of millet soup with noodles, and also with certain sociopsychological factors, in both areas. A large increase in risk was found with consumption of boiled vegetables in Linfen, with a dose-response relationship. EC risk tended to become greater with the increasing intake of moldy foods and of pickled vegetable juice. A positive association between EC risk and family history of EC was observed only in Yangcheng. Soybean consumption was found to be associated with reduced risk. Dental hygiene (brushing teeth) was associated with reduced risk in Linfen. There was a suggestion of increased risk associated with heavy tobacco smoking, but it was not significant in either area. Alcohol consumption had a marginally significant association with risk in the high risk area, but not in Linfen.

Esophageal cancer is one of the most common fatal cancers worldwide. Deletions of genomic regions are thought to be important in esophageal carcinogenesis. We conducted a genomewide scan for regions of allelic loss using microdissected DNA from 11 esophageal squamous‐cell carcinoma patients with a family history of upper gastrointestinal tract cancer from a high‐risk region in north central China. Allelic patterns of 366 fluorescently labeled microsatellite markers distributed at 10‐cM intervals over the 22 autosomal chromosomes were examined. We identified 14 regions with very high frequency (≥ 75%) loss of heterozygosity (LOH), including broad regions encompassing whole chromosome arms (on 3p, 5q, 9p, 9q, and 13q), regions of intermediate size (on 2q, 4p, 11p, and 15q), and more discrete regions identified by very high frequency LOH for a single marker (on 4q, 6q, 8p, 14q, and 17p). Among these 14 regions were 7 not previously described in esophageal squamous‐cell carcinoma as having very high frequency LOH (on 2q, 4p, 4q, 6q, 8p, 14q, and 15q). The very high frequency LOH regions identified here may point to major susceptibility genes, including potential tumor suppressor genes and inherited gene loci, which will assist in understanding the molecular events involved in esophageal carcinogenesis and may help in the development of markers for genetic susceptibility testing and screening for the early detection of this cancer. Genes Chromosomes Cancer 27:217–228, 2000. Published 2000 Wiley‐Liss, Inc.

Allelic loss on chromosome 17p has been reported frequently in esophageal squamous cell carcinoma (ESCC) and generally encompasses the p53 locus at 17p13.1. However, a good correlation between allelic loss on 17p and mutation of p53 has not been found. This suggests the possibility that unknown tumor suppressor genes near p53 may be involved in the development of ESCC. To evaluate this possibility, we analyzed 30 microsatellite markers covering the entire short arm of chromosome 17 in 56 ESCC patients from a high risk population in northern China, including 34 with a family history of upper gastrointestinal (UGI) cancer and 22 without a family history of any cancer. Cancer lifestyle risk factors and clinical/pathological characteristics were also collected. We found frequent allelic loss (>/=65%) at 28 of the 30 markers evaluated in these ESCC patients. The highest frequencies of allelic loss (> or =80%) were found in three smaller regions: deletion region I located at 17p13.3-p13.2 (between D17S849 and D17S1828); deletion region II located at 17p13.2-p13.1 (between D13S938 and TP53); deletion region III located at 17p13.1-p12 (between D17S804 and D17S799). A number of genes have already been identified in these deleted regions, including: OVCA1, OVCA2 and HIC-1 in deletion region I; p53 in deletion region II; ZNF18, ZNF29, ALDH3 and ALDH10 in deletion region III. These results will help us direct future testing of candidate genes and narrow the search region for major new tumor suppressor genes that may play a role in the pathogenesis of ESCC.