Faculty Bibliography

The mortality risk of nonmalignant respiratory disease among hematite workers in the Longyan and Taochong mines of China was investigated in a retrospective cohort study covering the period 1970-1982. The cohort was limited to men and consisted of 5406 underground miners, of whom 1335 (25%) were diagnosed as having silicosis. Among those with silicosis, 560 (42%) were diagnosed as having silicotuberculosis. Among the 490 underground miners who died, 278 (57%) died of nonmalignant respiratory disease. The relative risk for death due to nonmalignant respiratory disease for stage III silicotics compared to nonsilicotics was almost 100-fold. High dust exposure was associated with a statistically significant increase in risk of death due to nonmalignant respiratory disease (relative risk 5.3). The relative risk associated with jobs with high dust exposure before the introduction of industrial hygiene controls was 7.7, and the corresponding value for after their introduction was 2.3. There is a need for continued close monitoring of industrial hygiene in these mines

The biological activity of recombinant Interleukin-2 (rIL-2) administered intraperitoneally (ip) has not been determined and may differ significantly from the maximum tolerated dose (MTD). In this trial, the pharmacokinetics, toxicity, and biologic activity of a single ip dose were studied initially followed a week later by a 5-day ip rIL-2 given for 2 weeks every 28 days. Planned dose escalation was from 2 x 10(3) to 2 x 10(7) U given in 2 liters of D5W. Drug was obtained from the NCI and was administered through an ip port. Four patients received 1 U/ml and four patients received 10 U/ml. Preliminary data demonstrate an increase in the peritoneal fluid mononuclear cell count. Mononuclear cell phenotyping tested in the first eight patients showed a modest increase in Leu 2a+, Leu 15- cells, corresponding to CTL. A similar increase in Leu 19+ cells was also demonstrated (NK cells). Soluble IL-2 receptor was elevated in peritoneal fluid. Cytotoxicity against K562 and Daudi cell lines was not observed at the first two dose levels. Toxicity of treatment was minimal and related to abdominal distention. No objective responses were seen but in one patient we documented a reduction in serum CA-125 levels. The observed biologic response and lack of toxicity is promising and justifies further exploration of this immune-modulating approach

The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer

The concept of latency period has developed in chronic disease epidemiology by analogy with the incubation period associated with infectious diseases. We discuss the use of the concept of mean latency period to describe the temporal development of cancer and the underlying conceptual and methodologic problems. The respective roles of age at diagnosis, age at start of exposure, duration of exposure, and years since exposure in modifying cancer risks are considered. Multistep models for the development of cancer are illustrated, and their use and limitations for interpreting temporal associations in cancer development are discussed. Rather than trying to define exposure-disease relationships as being characterized by a long or a short latency period, it seems more promising to study the temporal sequence of disease development as a multistep process

The association between employment in motor exhaust-related occupations and the risk for lung cancer was examined in 2,291 male cases of lung cancer and 2,570 controls in data pooled from three U.S. case control studies carried out by the National Cancer Institute between 1976 and 1983. Most analyses were limited to subjects providing direct, in-person interviews, including 1,444 cases and 1,893 controls. For those providing direct interviews and employed 10 years or more in motor exhaust-related (MER) occupations, the age, smoking, and study area adjusted odds ratio (OR) for lung cancer was 1.5 (95% CI = 1.2-1.9). Risk was elevated for truck drivers (OR = 1.5; 95% CI = 1.1-1.9) and for other MER occupations (OR = 1.4; 95% CI = 1.1-2.0). The odds ratios associated with MER employment of 10+ years were 1.6 (95% CI = 1.2-2.1) for whites and 1.4 (95% CI = 0.9-2.1) for nonwhites; 1.2 (95% CI = 0.7-2.0) [corrected] for those with possible exposure to other recognized or reported lung carcinogens; and 1.6 (95% CI 1.2-2.1) for those without such exposure. The 50% excess risk for lung cancer associated with employment in motor exhaust-related occupations could not be explained by greater use of cigarettes or by other occupational exposures among these workers

Demographic risk factors for prostatic cancer were examined in a case-control study of 100 triplets of prostatic cancer patients and age-, hospital-, and admission date-matched control series of benign prostatic hyperplasia (BPH) patients and general hospital patients. A higher risk of prostatic cancer was associated with the following factors: 1) long-term occupation in transport or communication (relative risk [RR] = 4.92, 95% confidence interval [CI]: 1.18-20.5) as compared with hospital controls; 2) the wife having a lower educational level (RR = 1.88, 95%CI: 1.02-3.45) as compared with hospital controls; 3) no past episode of hypertension as compared with BPH controls (RR = 2.30, 95%CI: 1.27-4.15); 4) having several sisters (more than four) as compared with both BPH and hospital controls (RR = 3.82, 95%CI: 1.35-10.8 and RR = 2.94, 95%CI: 1.08-8.03 respectively); 5) dense body hair as compared with hospital controls (RR = 4.28, 95%CI: 1.19-15.4). No significant links were found with blood type, daily drug use, head hair, skin color, body type, smoking habits, religion, body weight, and mental characteristics

A study of mortality among 1,879 male workers employed in a New Jersey chromium pigment factory was carried out, with follow-up from 1940 to 1982. Vital status of 1,737 (92%) of the eligible cohort members was determined. For all malignant neoplasms, 101 deaths were observed while 108.8 were expected, SMR = 93 (standardized mortality ratio; n.s.). For the entire study group, no significant excess was observed for respiratory cancer or cancer at other sites. However, the total number of years of employment in the factory and the total number of years of exposure to chromate dusts were both statistically significantly (p less than .05, for trend) associated with an increased risk for lung cancer. The excess risk for lung cancer associated with duration of exposure to chromate dusts was, however, only clearly apparent for subjects followed for 30 years or more after initial employment. For this group, the SMRs were 81, 139, 201, and 321 for the subjects with 0 years, less than 1 year, 1-9 years, and 10+ years of exposure to chromate dusts (p less than .01, for trend), respectively. The risk for digestive cancer was only weakly associated with exposure to chromate dusts

Occupational data from 5 case-control studies in the United States involving 2,973 male cases and 3,210 controls were analyzed to estimate the percentage of lung cancer attributable to well-known and suspected lung carcinogens. The studies were conducted in areas heterogeneous in terms of industrial activities. The percentage of lung cancers attributable to occupations entailing potential exposure to well-recognized carcinogens ranged, by study area, from 3 to 17%. The further inclusion of occupational groups with suspect carcinogenic exposures changed these estimates very little. Exclusion of data derived from next-of-kin interviews influenced the estimates of attributable risks, but not in a systematic fashion. The estimates also varied according to ethnic group, smoking status and birth cohort, with higher values in non-whites, non-smokers and among members of more recent birth cohorts. Possible errors in exposure classification, which may make these estimates conservative, are discussed

Levels of retinol, beta carotene, and alpha tocopherol were assayed by high performance liquid chromatography (HPLC) in serum from subjects with clinical prostatic cancer (n = 94), focal prostatic cancer (n = 40), benign prostatic hyperplasia (n = 130), and from hospital controls (n = 130). Levels of beta carotene and alpha tocopherol varied for prostatic cancer patients by disease stage and by the period in the treatment sequence when blood was collected. This made any assessment of their association with prostatic cancer risk difficult. The mean level of serum retinol was significantly lower (P less than 0.05) in prostatic cancer patients than in the controls. For serum retinol this difference did not appear to be attributable to age, stage of disease, period in which the blood was collected, or to several other potentially confounding factors. When the serum retinol level was considered in quintile classes, there was a statistically significant (P less than 0.05) trend of increased prostatic cancer risk associated with decreasing serum retinol levels

Several epidemiologic studies have investigated the association between cancer risk and employment in chromium producing and using industries. Strong and consistent associations have been found between employment in the primary chemical producing industry and the risk for respiratory cancer. Workers employed in chromate pigment production and possibly spray painters of chromate pigment paints appear to be at excess risk of respiratory cancer. Chrome platers may also be at excess risk, although the evidence is limited. A few studies indicate that chromium alloy welding may also be an exposure source of concern. Some studies of ferrochromium alloy workers have shown an excess risk for respiratory cancer, although the risk may in part be due to concomitant exposures. The evidence indicates that the hexavalent form of chromium is the primary agent of chromium carcinogenesis. Solubility and other characteristics of chromium compounds may also play a role in determining risk