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Biomedical subjects

G N Stemmermann

Publications and source records attributed to G N Stemmermann.

At least 19 recordsLinked to original sources

Adenocarcinoma of the proximal small intestine. A marker for familial and multicentric cancer?

BACKGROUND: Adenocarcinoma of the small intestine is uncommon. The Hawaii Tumor Registry (HTR) has identified 49 of these tumors since 1960, and the Japan-Hawaii Cancer Study (JHCS) has identified only four of these tumors among a cohort of 8006 Hawaiian-Japanese men followed up for a period of 22 years. Each of the four men reported by the JHCS had multicentric gastrointestinal cancers. METHODS: Newly diagnosed cancers are recorded separately by the HTR and JHCS, and linkage is maintained between the two files. Family histories are available from the JHCS, and these are supplemented by a state population file maintained by the Department of Genetics, University of Hawaii. RESULTS: Five men, all Japanese, were found to have carcinoma of the proximal small intestine. Each had multicentric carcinomas of the gastrointestinal tract. Carcinoma of the stomach and colon was found in the primary relatives of each of four men whose families lived in Hawaii. CONCLUSIONS: The familial clustering of uncommon neoplasms (small bowel carcinoma and multicentric large bowel carcinoma), and the concurrence of gastric and colonic carcinoma suggests that these subjects have a genetic trait that increases susceptibility to a broad range of carcinogens.

Adenocarcinoma

Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet.

BACKGROUND: Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. PURPOSE: The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. METHODS: p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. RESULTS: Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. CONCLUSION: Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. IMPLICATIONS: The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC.

Adult

A prospective study of gastric and duodenal ulcer and its relation to smoking, alcohol, and diet.

The effects of environmental exposures on the development of gastric and duodenal ulcers were investigated in a prospective study of 7,624 American men of Japanese ancestry in Hawaii. After 149,291 person-years of observation, there were 280 incident cases of gastric ulcer and 149 incident cases of duodenal ulcer. The risk of both gastric and duodenal ulcers progressively increased with increasing pack-years of cigarette smoking. In contrast, alcohol intake was not associated with either type of ulcer. The risk of gastric ulcer was positively associated with the use of table salt/soy sauce, but there was no association with the consumption of other oriental foods. The risk of duodenal ulcer was inversely associated with western style diet around 1940 and with bread intake of two or more servings per day. The authors did not find any protective or adverse effect of milk and fruit consumption on peptic ulcer risk.

Age Factors

Prospective study of the association of alcohol with cancer of the upper aerodigestive tract and other sites.

The association of alcohol consumption with cancers of the upper aerodigestive tract, hepato-biliary-pancreatic system, urogenital organs (except for prostate), and lymphohematopoietic tissue was evaluated in a prospective study of 6,701 American men of Japanese ancestry living in Hawaii. Compared with cancer-free subjects, subjects who subsequently developed cancers of the upper aerodigestive tract (oral-pharynx, esophagus, and larynx), liver, biliary tract, and lymphohematopoietic tissue consumed significantly larger amounts of total alcohol--mainly in the form of beer. Subjects who developed oral-pharyngeal and esophageal cancer also consumed larger amounts of wine and spirits. Because the upper aerodigestive tract cancers were associated positively with cigarette smoking, age-adjusted relative risks (RR) were calculated, based on joint exposure to cigarette smoking and heavy alcohol intake (greater than or equal to 30 ml/day) in this population. A markedly increased risk was observed among subjects who were both heavy alcohol drinkers and smokers (RR = 17.3, 95 percent confidence interval [CI] = 6.7-44.2), compared with subjects who who did not smoke and did not drink heavily. The risk for these cancers also was increased among heavy alcohol drinkers who were nonsmokers (RR = 8.6, CI = 2.1-36.0).

Aged

Prospective study of clinical gallbladder disease and its association with obesity, physical activity, and other factors.

The association of anthropometric measurements, serum tests, and life-style factors with the risk of clinical gallbladder disease was investigated in a prospective study of 7831 American men of Japanese ancestry in Hawaii. After 152,831 person-years of observation, 471 incident cases of gallbladder disease were diagnosed by histology or radiology. There was an increase in risk of gallbladder disease with a progressive increase in body mass index, height, pack-years of cigarette smoking, and diastolic blood pressure. There was a decrease in risk with an increase in physical activity, after controlling for the effect of other variables. There was also an inverse association with total caloric intake that could be related to dietary restriction in obese subjects or to the limitations of the 24-hr diet history. Serum cholesterol levels and the intake of total fat were not related to clinical gallbladder disease in this cohort.

Age Factors

Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.

Aged

Determinants of sex hormone levels in men as useful indices in hormone-related disorders.

Because the determinants of serum sex hormone levels in men have been infrequently studied, we investigated the relation of several personal characteristics to serum levels of testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2) and sex hormone-binding globulin (SHBG) among 98 Japanese American men in Hawaii, aged 52-74. The SHBG levels and T/(E1 + E2) ratios decreased progressively with increasing body mass index. The SHBG levels were also inversely associated with hematocrit levels. Serum androgen and estrogen levels did not correlate with smoking, alcohol intake, serum cholesterol, serum uric acid and blood pressure. Some of the associations observed in the present study may be implicated in the etiology of hormone-related neoplasms in men.

Aged

A prospective study of the attributable risk of cancer due to cigarette smoking.

BACKGROUND: The goals of this study were to measure the impact of cigarette smoking on cancer incidence and to determine the attributable risk of cancer due to smoking. METHODS: A cigarette smoking history was obtained from 8006 Japanese-American men examined from 1965 through 1968. After 22 years, 1389 incident cases of cancer were identified. There were 212 men with lung cancer; 202 with oral, esophageal, laryngeal, pancreatic, renal, ureteral, or bladder (oral-bladder) cancer; and 975 with cancer at other sites. RESULTS: Current smokers at time of examination had a higher incidence than nonsmokers for each of the three cancer site categories. Eighty-five percent of lung cancer cases diagnosed among current and never smokers can be attributed to cigarette smoking. The attributable risks were 46%, 16%, and 29%, respectively, for oral-bladder cancers, other cancers, and all cancers combined. In turn, the corresponding attributable risks were 60%, 26%, 13%, and 21% in comparing current smokers with past smokers. CONCLUSIONS: Current smokers can greatly reduce their risk of cancer, especially lung cancer, if they quit smoking.

Age Factors

The association of blood pressure with cancer incidence in a prospective study.

A cohort of 8,006 Japanese-American men living in Hawaii was examined from 1965 to 1968 and followed for about 20 years. The study identified 1,155 incident cases of histologically confirmed cancer and 648 deaths due to cancer. There was no association between systolic or diastolic blood pressure and total cancer incidence or deaths due to cancer. The relative risk was 1.03 for cancer incidence and 1.00 for cancer mortality for subjects with a systolic pressure of 160 mmHg or greater. Adjustment was made for age, smoking, alcohol, and measures related to obesity. When cancers of specified sites were studied, blood pressure was positively associated with the incidence of kidney cancer (17 cases). After adjustment for the significant effect of taking antihypertensive medication, the effect of blood pressure became nonsignificant. Among seven other cancer sites, there were no statistically significant associations with blood pressure after adjustment for confounding factors.

Antihypertensive Agents

Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii.

BACKGROUND: Helicobacter pylori are gram-negative spiral bacteria that are associated with chronic gastritis, a known precursor of gastric carcinoma. Persons at high risk for gastric carcinoma have been shown to have a high prevalence of H. pylori infection. METHODS: We studied the relation of H. pylori infection and gastric carcinoma in a cohort of Japanese American men living in Hawaii. The 5908 men were enrolled and examined from 1967 to 1970. By 1989, 109 cases of pathologically confirmed gastric carcinoma had been identified. The store serum of each patient with gastric carcinoma and of each matched control subject were tested for the presence of serum IgG antibody to H. pylori. RESULTS: Ninety-four percent of the men with gastric carcinoma and 76 percent of the matched control subjects had a positive test for H. pylori antibodies, for an odds ratio of 6.0 (95 percent confidence interval, 2.1 to 17.3). As the level of antibody to H. pylori increased, there was a progressive increase in the risk of gastric carcinoma (P for trend = 0.0009). The association was strong even for men in whom the diagnosis was made 10 or more years after the serum sample was obtained (odds ratio, 10.5; 95 percent confidence interval, 2.5 to 44.8). CONCLUSIONS: Infection with H. pylori is strongly associated with an increased risk of gastric carcinoma. However, most persons infected with H. pylori will never have gastric carcinoma. Therefore, other factors that increase the risk of gastric carcinoma among persons infected with H. pylori need to be identified.

Antibodies, Bacterial

Prospective study of serum cholesterol levels and large-bowel cancer.

Based on previous reports, it is uncertain whether serum cholesterol levels are inversely related to colon cancer risk. In this study, serum cholesterol levels were measured in 7926 Japanese-American men who were followed for over 20 years. Two hundred thirty-one incident cases of colon cancer and 97 cases of rectal cancer were identified. An increase in serum cholesterol levels was associated with a decrease in risk for colon cancer (P value for trend = .01) but not for rectal cancer. This association appeared stronger as the site of cancer moved from the sigmoid colon to the cecum. The data were further analyzed by interval from examination to diagnosis. The inverse association was present for colon cancer cases diagnosed within 10 years of examination (P value for trend less than .01), especially for cecum-ascending colon cancer cases (P less than .01). A similar inverse pattern was found for cecum-ascending colon cancer cases diagnosed after 10 years, but the association was not statistically significant. The results suggest that the preclinical effects of undiagnosed colon cancer contributed to the inverse association, but these effects do not entirely explain why the relationship with hypocholesterolemia was stronger in men who were subsequently diagnosed with right-sided colon cancer.

Aged

The pathology of breast cancer in Japanese women compared to other ethnic groups: a review.

Review of comparative pathology studies of breast cancer among Japanese women and other ethnic groups reveals consistent differences in tumor morphology and host response. Japanese women show lower rates of breast cancer than Caucasian women, a difference that is accounted for by increased rates of this cancer in postmenopausal Caucasian women. Postmenopausal breast cancer is also less common among Japanese who migrated to a western environment. Autopsy studies of Japanese women without breast cancer indicate a lower prevalence of ductal hyperplasia, a breast cancer precursor, among indigenous Japanese women and first generation migrants than among second generation Japanese women in Hawaii who have higher rates of breast cancer. Postmenopausal breast cancers in Caucasian women are more likely to have estrogen receptors than cancers in postmenopausal Japanese women or premenopausal women of either race. Postmenopausal Japanese women are more likely to have in situ tumors than Caucasian women, even after adjusting for tumor size. A more vigorous host response to breast cancer among Japanese women, as compared to Caucasians, is suggested by more intense lymphocytic infiltration, greater degrees of lymph node sinus histiocytosis and fewer lymph node metastases in the Japanese.

Asian People

Cancer incidence following subtotal gastrectomy.

Hawaiian Japanese men (n = 432) who had undergone subtotal gastrectomy for peptic ulcers before 1971-1975 were followed up for detection of cancer development. They showed a significant increase in colon cancer risk (P = 0.008) and lung cancer risk (P = 0.002) compared with 6161 nongastrectomized men. The association with lung cancer persisted after adjustment for cigarette use (P = 0.03). Alcohol consumption was associated with colonic cancer in this cohort, and gastrectomized men consumed more alcohol than nongastrectomized men; however, the association of gastrectomy with colon cancer persisted after adjustment for alcohol use (P = 0.02). Gastrectomized men were lighter and had lower serum lipid levels than controls, suggesting that undernutrition might favor the development of some cancers. The type of gastroenteric anastomosis did not influence the cancer risk level in the colon or lung.

Alcohol Drinking

The effects of non-response in a prospective study of cancer: 15-year follow-up.

Out of 11,136 Japanese men identified on the island of Oahu, Hawaii in 1965 by the Honolulu Heart Program, 8006 responded to a mailed questionnaire and were examined. Some 1871 responded only to the mailed questionnaire, and 1259 did not respond at all. After 15 years of follow-up, the examined men had significantly lower risk of death from all causes and death from cancer. Minor differences were also noted between the two groups in the risk of cancer of the lung, stomach, colon, and rectum. However, the examined men had a significantly higher risk of prostate cancer. In general, the strength of these non-response effects was mainly due to risk differences in the first five years of the 15-year follow-up period. The relative risk (RR) of each of the seven endpoint events tended towards 1.0 as each of the three successive five-year follow-up intervals were considered. An exception to this was the prostate cancer incidence RR which favoured the unexamined men throughout the entire 15 years, but significantly so only in the last five-year follow-up interval. When the 8006 examined and 1871 unexamined men who responded to the mailed questionnaire were evaluated with respect to the association of cigarette smoking with lung cancer incidence, the RR for smokers was 9.77 for the examined men, and 6.73 for the unexamined men. Since these RRs are not significantly different, there should be little bias in RR estimates of cigarette smoking for lung cancer if the observation was limited to only the examined men. With regard to the association of body mass index (BMI) with colon cancer in older men, the RRs for men in the highest BMI quintile were quite comparable, at 1.37 for the examined group and 1.60 for the unexamined men. We conclude that although some non-response effects on cancer incidence exist in this cohort, they do not appear to be serious enough to have changed conclusions drawn about risk relationships.

Bias

Ciliated gastric cells among Japanese living in Hawaii.

A total of 129 consecutive gastrectomy specimens from Japanese (99), Philippinos (11), Hawaiians (8), Koreans (5), Chinese (4) and Caucasians born in Hawaii (2) were examined under high-power light microscopy (1000 x) for the presence of ciliated gastric cells. Fifty-two of the 129 gastrectomy specimens (40.3%) contained ciliated cells. Ciliated cells were found in the basal segments of antral glands (usually cystically dilated) whose superficial segments had undergone intestinal metaplasia. The presence of ciliated cells in the gastric mucosa was influenced by the age of the patient and by the degree of intestinal metaplasia: the older the patient, the greater the degree of intestinal metaplasia and the greater the frequency of specimens with ciliated cells. The presence of ciliated cells was also influenced by the type of lesion in the specimen. Although the highest frequency (47.2%) was found in stomachs removed for adenocarcinoma, a substantial number of stomachs removed for gastric ulcer also showed that change (36%). The data suggest that increasing age and advanced atrophic gastritis, especially of the antrum, provide the necessary conditions that lead to the development of cilia, not only in Japanese subjects, but in other Hawaiian ethnic groups as well.

Adult

Cancer incidence in Hawaiian Japanese: migrants from Okinawa compared with those from other prefectures.

Japanese men in Hawaii whose ancestral roots were in Okinawa were compared to Japanese migrants from all other prefectures. The Okinawan migrants have acquired fewer cancers than men from other prefectures (P = 0.12). No one primary site accounts for this difference. Stomach cancer rates showed the largest difference between the two migrant groups. This replicates the experience of Okinawans and non-Okinawans in Japan itself. Lymphosarcoma mortality rates are much higher in Okinawa than in all Japan, but this difference is not reproduced in Hawaiian migrants. This could be explained by a post migrational decrease in HTLV-I-related acute T-cell lymphoma/leukemia. Cancer of the mouth, pharynx and esophagus has decreased in all Japanese migrants, but the decrease is much greater among Okinawan migrants, suggesting they have escaped exposure to risk factors peculiar to the Okinawan environment. Colon cancer is more common in migrant Japanese than in U.S. whites. The dramatic increase in the frequency of this tumor affects Okinawan and non-Okinawan migrants to an equal degree.

Adult

Prospective study of pulmonary function and lung cancer.

The role of pulmonary function as an independent predictor of lung cancer risk was studied in a community-based cohort of 6,317 Japanese-American men who were aged 45 to 68 at the time of examination. After a follow-up period of about 22 yr, 172 incident cases of lung cancer were identified. The percentage of the predicted FEV1 was inversely related to lung cancer (p value for trend = 0.01) after adjustment for age and cigarette smoking history. The subjects in the lowest quartile of pulmonary function (% predicted FEV1 less than 84.5) had a relative risk of 2.1 (95% confidence interval = 1.3 to 3.5) for lung cancer compared with subjects in the highest quartile (% predicted FEV1 = 103.5+). For the 84 cases with a squamous or small cell histologic type of lung cancer, the subjects in the lowest quartile had a relative risk of 2.5 (95% Cl = 1.2 to 5.6) compared with subjects in the highest quartile of pulmonary function. For the 84 patients with lung cancer whose tumors were located within 4 cm of the pulmonary hilum, the subjects in the lowest quartile had a relative risk of 4.0 (95% Cl = 1.7 to 9.7). The results suggest that impaired pulmonary function in a community-based population is a predictor of lung cancer.

Aged