Gary D. Friedman

Helicobacter pylori Infection and the Risk of Gastric Carcinoma

BACKGROUND Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition.

Helicobacter pylori infection and gastric lymphoma

BACKGROUND Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkins lymphoma. METHODS This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkins lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkins lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay. RESULTS Thirty-three cases of gastric non-Hodgkins lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkins lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0). CONCLUSIONS Non-Hodgkins lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

A Case–Control Study of Screening Sigmoidoscopy and Mortality from Colorectal Cancer

BACKGROUND The efficacy of sigmoidoscopic screening in reducing mortality from colorectal cancer remains uncertain. A randomized trial would be ideal for clarifying this issue but is very difficult to conduct. Case-control studies provide an alternative method of estimating the efficacy of screening sigmoidoscopy. METHODS Using data on the 261 members of the Kaiser Permanente Medical Care Program who died of cancer of the rectum or distal colon from 1971 to 1988, we examined the use of screening by rigid sigmoidoscopy during the 10 years before the diagnosis and compared it with the use of screening in 868 control subjects matched with the case subjects for age and sex. RESULTS Only 8.8 percent of the case subjects had undergone screening by sigmoidoscopy, as compared with 24.2 percent of the controls (matched odds ratio, 0.30; 95 percent confidence interval, 0.19 to 0.48). Adjustment for potential confounding factors increased the odds ratio to 0.41 (95 percent confidence interval, 0.25 to 0.69). The negative association was as strong when the most recent sigmoidoscopy was 9 to 10 years before diagnosis as it was when examinations were more recent. By contrast, for 268 subjects with fatal colon cancer above the reach of the sigmoidoscope and for 268 controls, the adjusted odds ratio was 0.96 (95 percent confidence interval, 0.61 to 1.50). The specificity of the negative association for cancer within the reach of the sigmoidoscope is consistent with a true efficacy of screening rather than a confounding by unmeasured selection factors. CONCLUSIONS Screening by sigmoidoscopy can reduce mortality from cancer of the rectum and distal colon. A screening once every 10 years may be nearly as efficacious as more frequent screening.

CARDIA: study design, recruitment, and some characteristics of the examined subjects.

In 1984, a prospective cohort study, Coronary Artery Risk Development in Young Adults (CARDIA) was initiated to investigate life-style and other factors that influence, favorably and unfavorably, the evolution of coronary heart disease risk factors during young adulthood. After a year of planning and protocol development, 5,116 black and white women and men, age 18-30 years, were recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of major risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors. This report presents the recruitment and examination methods as well as the mean levels of blood pressure, total plasma cholesterol, height, weight and body mass index, and the prevalence of cigarette smoking by age, sex, race and educational level. Compared to recent national samples, smoking is less prevalent in CARDIA participants, and weight tends to be greater. Cholesterol levels are representative and somewhat lower blood pressures in CARDIA are probably, at least in part, due to differences in measurement methods. Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education.

Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection.

BACKGROUND AND AIMS: It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated. SUBJECTS: 242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected. METHODS: Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons. RESULTS: Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 < 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy. CONCLUSIONS: When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori are less strongly linked to malignancy and may only be associated with diffuse type disease.

Alcohol and mortality

OBJECTIVE To study the relation between alcohol intake and mortality in a large ambulatory population with attention to causes of death and differences related to age, sex, race, and baseline risk. DESIGN Prospective cohort study. SETTING Prepaid comprehensive health care program facilities in Oakland and San Francisco, California. PARTICIPANTS Adults (n = 128,934) who supplied data at health evaluations between 1978 and 1985. MEASUREMENTS Demographic data and health history were supplied using questionnaires. Death was ascertained by an automated linkage system and was individually validated. Relative risk for death at various levels of drinking was calculated by Cox proportional hazards models using lifelong nondrinkers as the reference and controlling for eight covariables. RESULTS Heavier drinkers were at greater risk for death from noncardiovascular causes (relative risk at greater than or equal to 6 drinks per day compared with no alcohol = 1.6, 95% Cl, 1.3 to 2.0) especially cirrhosis, unnatural death, and tobacco-related cancers. This alcohol-associated risk was higher in women (relative risk for death from all causes at greater than or equal to 6 drinks per day = 2.2; Cl, 1.4 to 3.8) and younger persons (for persons less than 50 years of age, relative risk for death from all causes at greater than or equal to 6 drinks per day = 1.9; Cl, 1.3 to 2.9). Lighter drinkers were at lower risk for death from cardiovascular disease, especially coronary heart disease (relative risk at 1 to 2 drinks per day = 0.7; Cl, 0.6 to 0.9), independent of baseline risk, with the greatest reduction of risk in older persons. Lighter drinkers over 60 years of age also had a slightly lower risk for noncardiovascular death, but this finding was not independent of baseline coronary heart disease risk. CONCLUSIONS Women and younger persons appear more susceptible to the increased mortality risk of heavy drinking. The reduced cardiovascular risk of lighter drinkers is more pronounced in older persons. Lower coronary disease prevalence may reduce the noncardiovascular mortality risk of lighter drinkers.

Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins.

SummaryConcordance for Type 2 (non-insulin-dependent) diabetes was determined in 250 monozygotic and 264 dizygotic white male twin pairs who participated in the National Heart, Lung, and Blood Institute Twin Study. These twins were born between 1917 and 1927 and were identified from military records without regard to disease status. We examined surviving members of the cohort twice — at mean ages of 47 and 57 years — and obtained 1-h post-load glucose tests and medication histories. Diagnostic criteria for Type 2 diabetes included a glucose value≥13.9 mmol/l or current use of antidiabetic medication; possible Type 1 (insulin-dependent) diabetic twins were excluded. A strong genetic predisposition to Type 2 diabetes was suggested by 3 lines of evidence from the second examination: (1) 58% of monozygotic co-twins of diabetic twins were themselves diabetic compared with an expected prevalence of 10%; (2) only 1 of 15 originally disease-discordant, monozygotic twin pairs remained discordant for diabetes; and (3) 65% of non-diabetic monozygotic co-twins of diabetic twins had elevated glucose values. Because concordance for diabetes was less than 100% for twins aged 52–65 years and because twins varied in age at onset of disease, non-genetic factors may also influence diabetes development. Among the 19 monozygotic twins pairs discordant for diabetes, diabetic twins did not differ from their non-diabetic co-twins in obesity, diet, alcohol consumption, or education. However, compared with unrelated nondiabetic twins of the same ages, non-diabetic co-twins of diabetic twins gained more weight as adults (p<0.02) and had higher glucose levels (p<0.03).

The Leukocyte Count as a Predictor of Myocardial Infarction

Abstract The multiphasic-examination findings of 464 persons in whom a first myocardial infarction later developed were compared with those of two control groups, one matched for age, sex and race (ordinary controls), and the other matched in addition for standard coronary risk factors (risk controls). The total leukocyte count, measured, on the average, 16.8 months before the myocardial infarction, was strikingly related to development of infarction. The mean leukocyte count in cases was significantly higher (p<0.001) than in either control group. Ascending from lowest to highest quartile in the cases and ordinary controls the increase in risk of myocardial infarction associated with the leukocyte count was similar to that found for cholesterol and blood pressure. Cigarette smoking, which was strongly related to the leukocyte count, may account for about two thirds of the relation of the count to infarction. The leukocyte count may prove valuable in the routine assessment of risk of myocardial infarction...

Pain Tolerance: Differences According to Age, Sex and Race

The nature and extent of group differences in pain tolerance according to age, sex and race were examined. The method of pain tolerance determination was mechanical pressure on the Achilles tendon, performed on 41 , 119 subjects as part of the Kaiser-Permanente Automated Multiphasic Screening examination. The results showed that, on the average, a) pain tolerance decreases with age; b) men tolerate more pain than women; and c) Whites tolerate more pain than Orientals, while Blacks occupy an intermediate position. When the results of this study are compared with earlier work, it appears that, with increasing age, tolerance to cutaneous pain increases and tolerance to deep pain decreases.

Risk Factors in Coronary Heart Disease: An Evaluation of Several Serum Lipids as Predictors of Coronary Heart Disease: The Framingham Study

A T FRAMINGHAM, MASSACHUSETTS, the Na± \ . tional Heart Institute has been following 5,127 men and women aged 30 to 60 years in a study of factors related to the development of coronary heart disease (CHD) and hypertension. Data for a decade of follow-up studies of this population are available for analysis. From a study of those who have developed disease under observation in comparison to those who have remained free of the disease, factors of risk and susceptible individuals have been identified. The factors associated with excess risk that have been identified are: serum cholesterol level, blood pressure, cigarette smoking, vital capacity, relative weight, and certain electrocardiographic findings. Efforts are being made to assess the independent contribution of each of these factors to the development of coronary heart disease because of the therapeutic, preventive, and pathogenetic implications of this information. This report focuses on the serum lipids. Attempt will be made to assess the relative efficacy of the various lipids as predictors of coronary heart disease and to determine their independent contribution to risk of the development of the disease. The present report deals with three types of lipids: cholesterol, phospholipids, and various beta-lipoprotein fractions. The relationship of various indexes, based on these lipids, to development of disease will also be assessed. Evaluation of the serum triglycerides in relation to development of disease will not be included, since this measurement was introduced in the study too recently for prospective analysis.