Cigarette smoking and other risk factors for progression of precancerous stomach lesions.

BACKGROUND: Stomach cancer is generally thought to evolve through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. PURPOSE: Our purpose was to assess risk factors for intestinal metaplasia and gastric dysplasia arising from chronic atrophic gastritis in a general population at high risk for stomach cancer. METHODS: A population-based gastroscopic screening of more than 3000 residents was conducted in a county in China with one of the world's highest rates of stomach cancer. Information on the lifestyle and other characteristics of the participants was obtained by interview, and responses were compared between those in whom the most advanced gastric lesion was dysplasia or intestinal metaplasia versus those with chronic atrophic gastritis. RESULTS: Cigarette smoking was found to nearly double the risk of transition to dysplasia and to be a mild risk factor for intestinal metaplasia. Smoking accounted almost entirely for the 55% higher prevalence of dysplasia among men than among women. Risk of transition to dysplasia had a weak association with several dietary factors and was increased among those participants with a family history of stomach cancer and with blood type A. CONCLUSIONS: The findings provide strong evidence for a role of tobacco consumption and offer clues to other environmental and genetic factors involved in the process of gastric carcinogenesis.

Precancerous gastric lesions in a population at high risk of stomach cancer.

A population-based screening for detection of early cancers evaluated the prevalence of precancerous gastric lesions in an area in Shandong province, China, with one of the world's highest rates of stomach cancer. A total of 3433 residents aged 35 to 64 yr received gastroscopical examinations with biopsies taken from standard locations. Chronic atrophic gastritis was nearly universal; less than 2% of the population had biopsies showing entirely normal mucosa or only superficial gastritis. Intestinal metaplasia was the most advanced lesion for 33% and gastric dysplasia for 20%, although the prevalence of each increased significantly with age. Intestinal metaplasia and gastric dysplasia were detected throughout the stomach, but the lesions were more pronounced along the lesser curvature, especially in the angulus and antrum. There was no sex difference in rates of chronic atrophic gastritis, but males had a slightly higher prevalence of intestinal metaplasia, a 1.6-fold increase in dysplasia, and a 3-fold excess of gastric cancer. The data quantify the extensiveness of gastric lesions likely to be involved in the natural history of stomach cancer in this high-risk population.

Technology transfer: a review for biomedical researchers.

Why is technology transfer important for cancer and other biomedical researchers? What do biomedical researchers need to know about technology transfer? This report will address these questions in the context of the United States technology transfer system, which is now approximately 20 years old. To accomplish this goal, this report first summarizes the importance of technology transfer and the role of intellectual property rights. Then it describes the sequential steps in technology transfer from universities to industry. Next, it describes technology transfer from the NIH intramural laboratories and other federal laboratories to industry. Finally, it describes unique aspects of technology transfer involving clinical trials. URL citations to the latest federal guidelines and regulations governing technology transfer are provided. Where appropriate, comparisons will be made with technology transfer systems in other countries. I hope that this step-by-step description of the technology transfer process will enable cancer researchers to play a more proactive role in this process and thus increase the likelihood that their discoveries will be successfully commercialized. I also hope that this report will assist such researchers to understand the policy and institutional considerations that underlie current debates concerning technology transfer.

Risk factors for stomach cancer in sixty-five Chinese counties.

Stomach cancer mortality data were compared with dietary and biochemical data from 65 Chinese counties to provide clues to reasons for the marked geographic variation of stomach cancer mortality rates in China. Sex-specific correlation and multivariate regression analyses showed significant positive associations with consumption of salted vegetables and eggs, prevalence of antibodies to Helicobacter pylori, and levels of plasma albumin; and significant negative associations with intake of green vegetables and levels of plasma selenium and beta-carotene. Limitations of ecological data preclude causal inferences, but these findings suggest factors that may contribute to making stomach cancer the leading cause of cancer death in China and other countries.

Serum pepsinogens in relation to precancerous gastric lesions in a population at high risk for gastric cancer.

Concentrations of serum pepsinogens (PG) I and II were determined for 3252 randomly selected adults who participated in a population-based gastroscopic screening in an area of China with one of the world's highest rates of gastric cancer. PG I and II concentrations in both sexes tended to be higher than reported in other countries, with levels generally higher among males than females. PG I tended to decrease and PG II to increase with age, but the most pronounced associations were between PG I:II ratios and gastric histology. Median PG I:II ratios monotonically declined from 9.1 to 7.2 to 5.7 to 5.4 to 3.8 among those with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and stomach cancer, respectively. The prevalence of dysplasia was nearly 3 times greater among those with PG I:II ratios less than 3 compared with those whose PG I:II ratios were greater than 10. While average levels differed significantly among the histologic groups, the PG I:II ratios were neither sensitive nor specific markers of an individual's likelihood of advanced gastric lesions in this population.

Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population.

Helicobacter pylori infection is a major cause of gastritis and may be a key risk factor for stomach cancer, but its role in the process of gastric carcinogenesis is not well understood. Herein, we examine H. pylori prevalence in relation to demographic and lifestyle factors and to severity of precancerous lesions in an area of China with one of the highest rates of stomach cancer in the world. H. pylori serum IgG antibody positivity was assayed among 2646 adults, ages 35-64, participating in a population-based gastroscopic screening survey in the high-risk area. The prevalence of positivity was evaluated according to gastric histology, environmental and lifestyle variables determined by interviews during the screening, and level of serum pepsinogens. The odds of advanced precancerous lesions (intestinal metaplasia and dysplasia) of the stomach among those with antibody positivity were estimated by logistic regression. Seventy-two % of the population was H. pylori antibody-positive, with nonsignificant variation by sex, age, income, education, family size, and cigarette smoking habits. H. pylori positivity was higher among those who ate sour pancakes, a fermented indigenous staple that is a risk factor for gastric dysplasia and stomach cancer in this population. The prevalence of H. pylori varied most notably, however, with gastric pathology. The percent of H. pylori positivity increased from 55 to 60 to 87% among those with superficial (nonatrophic) gastritis, mild chronic atrophic gastritis, and severe chronic atrophic gastritis, respectively, before falling to 78% among those with intestinal metaplasia or dysplasia. H. pylori antibody positivity also was strongly correlated with serum pepsinogen concentrations, particularly pepsinogen II, but knowledge of H. pylori status did not markedly improve serological identification of advanced precancerous lesions above that provided by pepsinogen ratios alone. The findings suggest that H. pylori infection contributes to the process of gastric carcinogenesis, particularly during the early stages, in this high-risk area.

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Apolipoproteins and coronary artery disease.

In this study, we compared the relative utility of plasma levels of cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins in identifying men with angiographically significant coronary artery disease in a combined sample of consecutive male patients undergoing coronary angiography (N = 304) and healthy, normal male control subjects (N = 135). The plasma apolipoprotein levels were measured by using specific radioimmunoassays. We found that plasma levels of apolipoprotein A-I, followed by those of apolipoproteins A-II and B, were better discriminators than plasma cholesterol, triglycerides, or HDL cholesterol levels for identifying those with coronary artery disease. In confirmation of previous findings, the presence of coronary artery disease resulted in lower levels of apolipoproteins A-I and A-II and HDL cholesterol and higher levels of apolipoprotein B, cholesterol, and triglycerides. Linear and quadratic discriminant function analysis demonstrated that by using the age of the patients and apolipoprotein A-I, A-II, and B levels, one could correctly classify patients either as being normal or as having angiographically significant coronary artery disease in more than 75% of the cases. Thus, plasma apolipoprotein levels (especially A-I and A-II) may be considerably better markers for coronary artery disease than traditional lipid determinations.

Cancer incidence following hospitalization for multiple sclerosis in Denmark.

Incidence of various cancers was evaluated in a cohort of 5359 multiple sclerosis (MS) patients, identified through hospital discharge records between 1977 and 1987 and followed for an average of 5.2 years. Computerized linkage with the Danish Cancer Registry uncovered 210 cancer cases which was significantly more than expected based on national rates (relative risk (RR) = 1.29). Over half of the excess, however, was observed for non-melanoma skin cancer and tumors of the urinary tract, which may be related to increased medical surveillance among MS patients compared to the Danish population as a whole. There was a significant excess of nasopharyngeal carcinomas in the cohort (RR = 17.3), but based on only 3 cases and seen only among women. Hematologic and lymphatic malignancies were not increased, adding little support to previous suggestions of a possible association of these malignancies with MS. An excess of brain tumors, seen only in women, may represent situations where the tumor caused symptoms which were interpreted as MS. Overall, the data suggest that a patient with MS is not at unusual risk for subsequent cancer development, but the relatively short follow-up of the population is a limitation of the investigation.

Rising incidence of adenocarcinoma of the esophagus and gastric cardia.

Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer. In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach. Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women. By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites. The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.

Etiological research on gastric cancer and its precursor lesions in Shandong, China.

Research over the past several years in an area of Shandong, China, with one of the world's highest rates of gastric cancer, has yielded clues to the environmental determinants of this tumour. Interviews with 564 gastric cancer patients and 1131 population-based controls revealed increased risks associated with consumption of sour pancakes, a fermented staple unique to the area, in samples of which volatile N-nitrosamines have been detected. Lower risks were found among people who had a higher intake of fresh vegetables, including garlic and other Allium vegetables which contain constituents that can inhibit carcinogenesis by N-nitrosamines and other substances in experimental animals. A pilot study involving assays of urine and gastric juice from 60 individuals in a screening programme showed higher levels of N-nitrosoproline and of cis- and trans-N-nitroso-2-methylthiazolidine 4-carboxylic acid among persons with gastric dysplasia than in either normal controls or those with chronic atrophic gastritis. We are trying to characterize the transition and progression of precursor lesions to gastric cancer and to evaluate the role of dietary variables, nutrients, N-nitroso compounds and other factors in particular stages of the carcinogenic process.

A cohort study of stomach cancer in a high-risk American population.

Demographic, smoking and dietary information was obtained from a cohort of 17,633 white American men, largely of Scandinavian and German descent, who responded to a mailed questionnaire in 1966. After 20 years of follow-up, 50% to 90% increases in mortality from stomach cancer (75 deaths) were found among foreign-born, their children, and among residents of the North Central states. An association was seen with low educational attainment and laboring or semiskilled occupations, primarily among immigrants and their children. Risk was evaluated in subjects who regularly smoked cigarettes (RR = 2.6, 95% CI = 1.1 to 5.8). A significant dose-response trend was observed, with subjects who smoked 30 or more cigarettes per day having more than a five-fold increased risk compared with those who never smoked. Elevated risks were also found for pipe smoking and smokeless tobacco use, but not for alcohol consumption. Analysis of dietary consumption of nine food groups revealed no significant associations with stomach cancer. However, total carbohydrate intake and a few individual food items (salted fish, bacon, cooked cereal, milk, and apples) were associated with increased risk. The findings of this prospective study of a high-risk population add to the limited evidence relating tobacco consumption to stomach cancer risk and suggest clues to ethnic, geographic, and dietary risk factors.

Occupational risk factors for gastric cancer in Shanghai, China.

Occupational data for over 13,000 incident stomach cancer cases reported to the Shanghai Cancer Registry between 1980 and 1984 were compared with 1982 census employment information to calculate standardized incidence ratios for stomach cancer in the Shanghai urban area. Several occupations were found to have statistically significantly increased risks for stomach cancer, most notably grain farming and several jobs involving potential for exposure to metal, wood, and other dusts and to fossil fuel combustion products. Because of the large numbers involved and consistency of associations, the findings raise hypotheses regarding occupational exposures that warrant further investigation.

Comparison of the anatomic distribution of stomach cancer and precancerous gastric lesions.

The anatomic distribution of precancerous gastric lesions among 3,400 residents in Linqu, Shandong Province of China, was compared with the anatomic distribution of stomach cancer (SC) among 959 patients in Tokyo, Japan. The incidence of SC is high in both areas, and locations within the stomach of the precancerous and malignant lesions were classified using similar criteria. Chronic atrophic gastritis (CAG) affected 98% of the population in Linqu, with intestinal metaplasia (IM) the most severe diagnosis in 33% and dysplasia (DYS) in 20%. Neither the SC nor precancerous lesions were uniformly distributed in the stomach. Among the DYS 3% were along the greater curvature of the body, 15% along the lesser curvature of the body, 25% in the angulus, 22% along the lesser curvature of the antrum, and 34% elsewhere in the antrum. Among the SC the corresponding percentages were 2, 16, 28, 25 and 29. The similarity to the SC distribution increased gradually from CAG to IM to DYS, providing further evidence for the multistage progression of precancerous gastric lesions.

Serum micronutrients in relation to pre-cancerous gastric lesions.

Serum levels of retinol, beta-carotene, ascorbic acid, alpha-tocopherol, selenium, ferritin, copper, and zinc were assayed for approximately 600 adults aged 35 to 64 with pre-cancerous gastric lesions in an area of China with one of the world's highest rates of stomach cancer. Previous studies have shown that the cancers generally are preceded by chronic atropic gastritis (CAG), intestinal metaplasia (IM) and dysplasia. Concentrations of beta-carotene and ascorbic acid were significantly lower among individuals with IM than among those whose most severe lesion was superficial gastritis or CAG. The associations with IM for these nutrients were strong and independent. In combination, the odds of CAG progressing to IM were only 1/6 as high among those with upper tertile levels of beta-carotene and ascorbic acid as among those with lower tertile levels of both nutrients. The serum levels of beta-carotene and ascorbic acid were similar for individuals having IM with or without accompanying dysplasia. Risk of IM was also somewhat increased among those with low serum ferritin, but no significant effects were observed in multivariate analyses for the other nutrients assayed. The findings point to a major influence of specific nutrient deficits in the mechanisms of gastric carcinogenesis in this high-risk area.