Age of gastric cancer patients and susceptibility to chronic gastritis in their relatives. A mathematical approach using Poisson's process and scoring of gastritis state.
OBJECTIVE: To estimate the risk of malignant diseases in families of probands with the same mutation in the BRCA2 gene. DESIGN: A cohort study using record linkage of a breast cancer family resource and the Icelandic Cancer Registry. SETTING: Iceland. SUBJECTS: Families of 995 breast cancer patients, from which 887 were tested for a single founder 999del5 mutation; 90 had the mutation and 797 did not. RESULTS: Relatives of probands with the mutation had significantly increased relative risk (RR) of breast cancer. For first degree relatives, the RR was 7.55 (95% CI 6.04 to 9.03) but was 1.72 (95% CI 1.49 to 1.96) in first degree relatives of probands without the mutation. For prostate and ovarian cancer, the first and second degree relatives of probands with the mutation had a significantly increased RR, but in families of probands without the mutation no significant familial risk was found. CONCLUSIONS: The 999del5 mutation in the BRCA2 gene explains a substantial proportion of familial risk of breast cancer in Iceland, but significant familial risk remains in relatives of probands without the mutation. For prostate and ovarian cancer, the mutation accounts for most of the familiality observed in families of breast cancer patients.
Epidemiology of intestinal and diffuse types of gastric carcinoma: a time-trend study in Finland with comparison between studies from high- and low-risk areas.
Reliable data on familial risks are important for clinical counselling and cancer genetics. However, the estimates of familial risk of gastric cancer vary widely. We examined the risk of familial gastric cancer using the updated Swedish Family-Cancer Database with 5358 patients among offspring and 36,486 patients among parents. There were 133 families with one parent and one offspring diagnosed with gastric cancer, and 20 families with two affected offspring. Familial standardised incidence ratios (SIRs) were 1.63 and 2.93 when parents and siblings presented with gastric cancer, respectively. The high sibling risk was owing to cancer in the corpus (SIR 7.28). The SIR for cardia cancer was 1.54 when parents were diagnosed with any gastric cancer. Cardia cancer associated with oesophageal cancer, particularly with oesophageal adenocarcinoma. Among specific histologies, signet ring cancer showed an increase. A few associations were noted for discordant sites, including the urinary bladder and the endometrium. H. pylori infection, although not measured in the present study, is probably an important risk factor for the high sibling risk of corpus cancer. Familial clustering of cardia cancer is independent of H. pylori infection, and may have a genetic basis. The familial association of cardia cancer with oesophageal adenocarcinoma may provide aetiological clues.
This report is devoted to the genetic study of stomach cancer within the limits of classic and multiple models. Also, analysis of phenotypic and genetic correlations in the system of stomach cancer--pre-cancer and that of the association of this disease with genetic markers were conducted. The reliable dependence of the development of stomach cancer on genetic factors is shown and its genetic stipulation with individual forms of ulcer disease and gastritic is determined. The problem of their genetic heterogeneity has been discussed based on these findings. The values of recurrence risk of the development of stomach cancer in population of Moscow and those of the expressivity of connection of ulcer disease forms and stomach cancer with genetic variants of the ABO and Rhesus systems were obtained.
Heredity predisposition was analysed in cancer and precancer stomach diseases in distinct populations. Some phenotypic and genetic characters of the stomach "precancer--cancer" system were studied. Similarity in the degree of stomach cancer inheritance, its segregation frequency and recurrent risk was revealed for populations. However, the degree of correlation between cancer and precancer stomach disease was different in distinct populations, this being more pronounced in "cancer--gastric ulcer" system.
BACKGROUND: Association between gastric cancer and environmental factors (diet and infections) has been established, and genetic changes are well described in adenocarcinomas of the stomach. Less is known about clinical features of hereditary gastric cancer and whether the disease is associated with family clustering. STUDY DESIGN: Family trees of patients diagnosed with gastric cancer in Iceland between 1955 and 1999 were identified in the Genealogical Database of the University of Iceland. All probands with age of onset younger than 60 years were used in the study. Families of all probands (n = 455 men and 161 women) were traced to third degree. Through linkage of the genealogic data obtained by the Icelandic Cancer Registry (between 1955 and 1999), all reported cancers were identified in those families. The expected number of cases was calculated using age-specific population rates in Iceland. RESULTS: A relative risk (RR) of 2.2 (95% confidence interval [CI] = 1.6-3.0) and 1.3 (95% CI = 1.0-1.7) for the gastric cancer risk was observed among 2,846 first- and 8,658 second-degree relatives of male probands. For female probands the corresponding relative risks were 1.6 (95% CI = 1.1-2.6, n = 7,396) and 1.4 (95% CI = 0.9-2.0, n = 2,764). The increased risk was more pronounced for relatives of men and women diagnosed with gastric cancer before the age of 50 years. A minor difference in relative risk was found between relatives of probands who were diagnosed with intestinal type or diffuse type gastric cancer. Fifty-eight families with two or more relatives with cancer were identified. In 32 families 2 relatives with gastric cancer were identified and in 26 families 3 or more relatives had gastric cancer. CONCLUSIONS: Relatives of gastric cancer patients have two- to three-fold increased risk of developing gastric cancer. The risk is elevated for both genders.
OBJECTIVE: Helicobacter pylori (H. pylori) infection stimulates the production of interleukin (IL)-1 beta, a pro-inflammatory cytokine and suppressor of gastric acid secretion. As both inflammation and hypochlorhydria, which might facilitate proximal colonization of H. pylori and other bacterial species alike, have been implicated in gastric carcinogenesis, much attention has been directed to functional genetic polymorphisms that affect the production of IL-1 beta. The purpose of this study was to clarify the role of these polymorphisms. MATERIAL AND METHODS: We analysed a population-based, case-control study in 5 Swedish counties and a hospital-based, case-control study conducted in 8 Swedish hospitals, with a total of 351 gastric cancer cases and 539 controls. The IL1B-31, IL1B-511 and IL1B+3954 biallelic polymorphisms were genotyped using pyrosequencing. The variable number of tandem repeats (VNTR) polymorphism of IL1-RN was analysed using polymerase chain reaction (PCR) followed by gel electrophoresis. Relative risks were estimated by odds ratios with 95% confidence intervals, derived from unconditional logistic regression. RESULTS: The risk of gastric cancer was unrelated to genotype in all of the studied polymorphic loci, and the absence of any association was confirmed in both the population-based and hospital-based case-control studies. Analyses confined to histological subtypes (intestinal or diffuse) and site-specific tumours (cardia or distal stomach), as well as analyses stratified by H. pylori infection status and family history of gastric cancer, did not reveal any significant increases or decreases in risk. CONCLUSION: Our results do not lend support to the hypothesis that human genetic polymorphisms related to the production of IL-1 beta are associated with the risk of gastric cancer.
A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene.
