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J F Fraumeni

Publications and source records attributed to J F Fraumeni.

At least 145 records · Page 8Linked to original sources
PubMed1996

Risks of non-Hodgkin's lymphoma, multiple myeloma, and leukemia associated with common medications.

We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97).

Adult↗
PubMed1996

Obesity and risk of renal cell cancer.

In a population-based case-control study including 449 directly interviewed cases and 707 controls, we assessed the risk of renal cell cancer associated with height, weight, body mass index (BMI), and frequency of weight changes. Odds ratios and 95% confidence intervals were estimated by using logistic regression models. Among women, risk increased with increasing usual BMI (P for trend < 0.001). A nearly 4-fold risk was found among the 10% of women with the highest usual BMI (odds ratio = 3.8; confidence interval = 1.7-8.4). Among men, no clear trend was observed with usual weight or BMI, although the highest risk (30-50%) generally was seen among those in the upper deciles of weight or BMI. There was no clear indication that excess BMI early or late in life disproportionately affected risks. Risk also was not related to patterns of weight fluctuations or use of diet pills. Our study supports previous observations linking renal cell cancer risk to increased BMI among women and suggests a weaker association in men. Given the increasing prevalence of obesity and the rising incidence of renal cell cancer in the United States, additional studies are needed to disentangle the effects of BMI from various correlates and to identify the mechanisms by which obesity affects risk.

Adult↗
PubMed1996

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.

Adult↗
PubMed1996

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.

Adult↗
PubMed1996

Smoking and adrenal cancer mortality among United States veterans.

Adrenal cancer is a rare and heterogenous group of tumors the etiology of which is largely unknown. Tobacco use was suggested as a potential risk factor in a recent case-control study of adults dying from adrenal cancers, most of which were adrenocortical carcinomas. In a cohort study of nearly 250,000 United States veterans whose mortality was followed for up to 26 years, we evaluated the risk of adrenal cancer associated with tobacco use. Relative risks and corresponding 95% confidence intervals were calculated. A total of 27 adrenal cancer deaths were observed during the follow-up period. Relative to nonusers of any tobacco, risk was elevated 5-fold (relative risk = 5.1; confidence interval = 1.1-22.4) among current cigarette smokers, with risks further increased among those who smoked > 20 cigarettes/day (P for trend < 0.01). Nonsignificant increases in risk occurred among smokers of other forms of tobacco. This cohort study provides support for an etiological relationship between tobacco smoking and adrenal cancer, although further confirmatory studies are needed.

Adrenal Gland Neoplasms↗
PubMed1995

Cancer in the parents of children with cancer.

BACKGROUND: Certain types of cancer in children and young adults have been linked with an increased risk of cancer in close relatives. However, the relation between childhood cancer and familial risk remains to be fully assessed in population-based studies. METHODS: We conducted a nationwide study in Denmark of 11,380 parents of children with cancer. The children were identified from records in the Danish Cancer Registry; their parents were identified from population registers. The occurrence and rate of cancer in the parents were determined with use of the Cancer Registry's files and compared with national incidence rates for various categories of tumor. RESULTS: Overall, 1445 cancers were diagnosed in the parents, as compared with 1496 expected from national incidence rates, to yield standardized incidence ratios of 1.0 (95 percent confidence interval, 0.9 to 1.0) for all parents, 1.0 for mothers, and 0.9 for fathers. The lower rate of cancer among fathers reflected their lower standardized incidence ratio for lung cancer (0.8; 95 percent confidence interval, 0.6 to 0.9), as calculated from 144 observations. CONCLUSIONS: Genetic determinants are important in several types of childhood cancer, but the genetic susceptibility to tumors does not generally extend to the parents of children with cancer, nor do the patterns of incidence point to the influence of shared environmental factors. Thus, cancer in children should not be viewed as a general marker for an increased risk of cancer in the patients' parents.

Adolescent↗
PubMed1995

The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia.

OBJECTIVE: To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). DESIGN: A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status. SETTING: A large prepaid health plan. SUBJECTS: Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. MAIN OUTCOME MEASURES: Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]). RESULTS: Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08) CONCLUSIONS: This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC.

Adenocarcinoma↗
PubMed1995

Analgesics and cancers of the renal pelvis and ureter.

To evaluate renal pelvis and ureter (RPU) cancer risk in relation to lifetime use of analgesics, a population-based case-control study was carried out in 3 areas of the United States. Among 502 cases and 496 controls diagnosed and interviewed during 1983-1986, no significant increases in risk were found for any of the non-prescription and prescription analgesics evaluated or among regular users of phenacetin, acetaminophen or aspirin. Neither cumulative lifetime ingestion nor duration of regular use of these 3 drugs, whether alone or in combination, was associated with significantly increased risk of RPU cancer, although a slight excess was observed among long-term users of acetaminophen. Risk was not increased among persons reporting highest cumulative dose and/or longest duration of phenacetin use. Although our study of RPU cancer is the largest to date, it was nonetheless limited by the small number of regular analgesic users and the relatively low response rates. Because of the relatively recent onset of widespread use of acetaminophen, its pharmacologic similarity to phenacetin, a known urothelial carcinogen, and the elevation in risk seen in long-term users, further surveillance of this analgesic is warranted.

Acetaminophen↗
PubMed1995

Mutations of the K-ras and p53 genes in gastric adenocarcinomas from a high-incidence region around Florence, Italy.

K-ras and p53 gene mutations in intestinal-type gastric carcinomas from a high-incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single-strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (including two at a previously unreported site in codon 11), a significantly higher frequency than reported in countries other than Japan. No K-ras mutations were identified in stage III tumors. Single-strand conformation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, with mutations identifiable by direct sequencing in 65% of the cases. Of these, 91% were base substitutions, a value similar to that usually reported, but the percentage of G:C to A:T transitions (90% in this study, 89% in all published European cases combined) differed significantly from that in Oriental cases (48%). The percentage of A:T to G:C transitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European tumors). The frequency of mutations at CpG sites (14%) varied significantly from the 67% in cases from a neighboring region in Italy. Helicobacter pylori infection was established in 19 cases and was somewhat more common in cases lacking a p53 mutation.

Adenocarcinoma↗
PubMed1995

Mutagens from heated Chinese and U.S. cooking oils.

BACKGROUND: The lung cancer incidence in Chinese women is among the highest in the world, but tobacco smoking accounts for only a minority of the cancers. Epidemiologic investigations of lung cancer among Chinese women have implicated exposure to indoor air pollution from wok cooking, where the volatile emissions from unrefined cooking oils are mutagenic. PURPOSE: This study was conducted to identify and quantify the potentially mutagenic substances emitted from a variety of cooking oils heated to the temperatures typically used in wok cooking. METHODS: Several cooking oils and fatty acids were heated in a wok to boiling, at temperatures (for the cooking oils) that ranged from 240 degrees C to 280 degrees C (typical cooking temperatures in Shanghai, China). The oils tested were unrefined Chinese rapeseed, refined U.S. rapeseed (known as canola), Chinese soybean, and Chinese peanut in addition to linolenic, linoleic, and erucic fatty acids. Condensates of the emissions were collected and tested in the Salmonella mutation assay (using Salmonella typhimurium tester strains TA98 and TA104). Volatile decomposition products also were subjected to gas chromatography and mass spectroscopy. Aldehydes were detected using high-performance liquid chromatography and UV spectroscopy. RESULTS: 1,3-Butadiene, benzene, acrolein, formaldehyde, and other related compounds were qualitatively and quantitatively detected, with emissions tending to be highest for unrefined Chinese rapeseed oil and lowest for peanut oil. The emission of 1,3-butadiene and benzene was approximately 22-fold and 12-fold higher, respectively, from heated unrefined Chinese rapeseed oil than from heated peanut oil. Lowering the cooking temperatures or adding an antioxidant, such as butylated hydroxyanisole, before cooking decreased the amount of these volatile emissions. Among the individual fatty acids tested, heated linolenic acid produced the greatest quantities of 1,3-butadiene, benzene, and acrolein. Separately, the mutagenicity of individual volatile emission condensates was correlated with linolenic acid content (r = .83; P = .0004). Condensates from heated linolenic acid, but not linoleic or erucic acid, were highly mutagenic. CONCLUSIONS: These studies, combined with experimental and epidemiologic findings, suggest that high-temperature wok cooking with unrefined Chinese rapeseed oil may increase lung cancer risk. This study indicates methods that may reduce that risk. IMPLICATIONS: The common use of wok cooking in China might be an important but controllable risk factor in the etiology of lung cancer. In the United States, where cooking oils are usually refined for purity, additional studies should be conducted to further quantify the potential risks of such methods of cooking.

China↗
PubMed1995

Recent cancer trends in the United States.

BACKGROUND: Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer. PURPOSE: We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns. METHODS: Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population. Similar rates were computed using national mortality data. Cancers were ranked according to the change in incidence rates over the two periods. RESULTS: Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due largely to rising rates for prostate cancer among men and for breast and lung cancers among women. National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining. Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non-Hodgkin's lymphoma, and melanoma among young and middle-aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons. CONCLUSIONS: Trends in cancer incidence and mortality differ. For most cancers, incidence rates are rising, while mortality rates are generally stable or declining. IMPLICATIONS: Much of the recent increase in cancer incidence can be explained by known factors. Improved detection appears to account for most of the increases in breast cancer among women and prostate cancer among men. On the other hand, cigarette smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non-Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified.

Age Distribution↗
PubMed1995

Reproductive factors and the risk of renal cell cancer among women.

In etiologic studies of renal cell carcinoma the role of reproductive variables and the use of exogenous hormones have not been well examined. In a population-based case-control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2-fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2-fold risk (OR = 2.2, 95% CI = 1.2-4.0) relative to those with 1 or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above-median body mass index than among those without these conditions. In addition, risk was reduced among long-term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study.

Adult↗
PubMed1995

Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark.

A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population.

Adult↗