Faculty Bibliography

BACKGROUND: Earlier reports of the mortality experience of this cohort of automotive workers followed from 1938 to 1967 who were exposed to cutting oil mist noted an excess of gastrointestinal cancer. The present report describes the mortality experience of these workers followed for mortality through 1980. METHODS: Cause-specific standardized mortality ratios were calculated by comparing the observed number of deaths to the expected numbers based on rates for the U.S. male population. RESULTS: The SMRs for liver and biliary tract, and testicular cancers were significantly elevated. Among the subset of workers with heavy oil mist exposure, SMRs were significantly elevated for cancers of the lung and testis, and for Hodgkin's disease. The risk of death due to lung cancer was greatest among workers with heavy exposure to oil mist employed for 15 or more years. Mortality due to stomach cancer was in excess among workers with heavy exposure to oil mist who were employed for 5 or more years. There were significant excesses of deaths due to asthma and emphysema. CONCLUSIONS: Further studies with information on the presence of contaminants and additives in oil mists will help elucidate the relationship between oil mist exposure and cancer

We propose a new approach to the additive dose method in EPR dosimetry studies for tooth enamel specimens. We outline a specialized routine whereby the sample may be left for the most part unirradiated, while only a small aliquot of the sample will be additively irradiated to relatively large doses. The routine is done in such a way so as not to significantly compromise either precision or accuracy of the dose reconstruction. It is also demonstrated that the overall throughput of the dose reconstruction is not appreciably compromised. With this potential ability, the utility of an international dose/sensitivity standard for EPR dosimetry of teeth is considered

Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used to assess multiplicative gene-environment interaction without inclusion of control subjects. A case-series interaction odds ratio (OR) > 1.0 indicates that the relationship of cigarette smoking and bladder cancer risk is stronger among slow acetylators as compared with rapid acetylators. We observed an interaction between smoking and N-acetyltransferase 2 slow acetylation (OR, 1.3; 95% confidence interval, 1.0-1.6) that was somewhat stronger when analyses were restricted to studies conducted in Europe (OR, 1.5; confidence interval, 1.1-1.9), a pooling that included nearly 80% of the collected data. Using the predominantly male European study population and assuming a 2.5-fold elevation in bladder cancer risk from smoking, we estimated that the population attributable risk percent was 35% for slow acetylators who had ever smoked and 13% for rapid acetylators who had ever smoked. These results suggest that the relationship of smoking and bladder cancer is stronger among slow acetylators than among rapid acetylators

A population-based case-control study was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer and 1315 controls (594 black, 721 white). In-person interviews elicited information on sexual behaviour and other potential risk factors for prostate cancer. Blood was drawn for serologic studies in a subset of the cases (n = 276) and controls (n = 295). Prostate cancer risk was increased among men who reported a history of gonorrhoea or syphilis (odds ratio (OR) = 1.6; 95% confidence internal (CI) 1.2-2.1) or showed serological evidence of syphilis (MHA-TP) (OR = 1.8; 95% CI 1.0-3.5). Patterns of risk for gonorrhoea and syphilis were similar for blacks (OR = 1.7; 95% CI 1.2-2.2) and whites (OR = 1.6; 95% CI 0.8-3.2). Risks increased with increasing occurrences of gonorrhoea, rising to OR = 3.3 (95% CI 1.4-7.8) among subjects with three or more events (Ptrend = 0.0005). Frequent sexual encounters with prostitutes and failure to use condoms were also associated with increased risk. Syphilis, gonorrhoea, sex with prostitutes and unprotected sexual intercourse may be indicators of contact with a sexually transmissible factor that increases the risk of prostate cancer

Oral epithelial cells provide an easily accessible source of germline DNA. Two methods for collection were compared in a 1992-1995 case-control study of oral cancer in Puerto Rico. One group of subjects (55 controls without oral cancer) collected oral rinse samples at home or work under the direction of a nonmedically trained interviewer ('self-collection'); the other group (94 controls) participated in a clinic-based collection, which also included blood and urine samples, conducted by a medical technician ('clinic collection'). Participation was higher for self-collection (98.2%) than for clinic collection (70.7%) (p < 0.001). DNA yields ranged from 2.0 to 204.5 microg (median, 25.9 microg) and did not differ by collection method, although yields varied by interviewer among self-collected samples (p = 0.02). Success rates for polymerase chain reaction amplification of the ADH3, NAT1, and multiplex CYP1A1/GSTT1/GSTM1 genotyping assays ranged from 76.4% (NAT1) to 98.2% (ADH3) for self-collected samples and were similar to those for clinic-collected samples (87.2-97.9%). Failure to amplify was associated with low DNA content (p = 0.015). Similar results were observed among cases (91 self-collected, 66 clinic collected), except that DNA yields did not vary by interviewer and a larger fraction (10.2%) of samples contained less than 5 microg of DNA, perhaps because of disease-related oral impairment. Self-collection of oral epithelial DNA samples appears satisfactory and efficient for many epidemiologic studies

While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure

BACKGROUND: In this analysis of European case-control studies on sinonasal cancer, we examined the risk for occupation and smoking, by gender and histological type. METHODS: The pooled data included 104 female and 451 male cases, and 241 female and 1,464 male controls. Lifetime smoking and occupational history were recoded following uniform criteria, and job-exposure matrices were applied for wood and leather dust. RESULTS: Wood dust exposure was associated with an excess risk in men (OR = 2.36, 95% CI 1.75-3.2) but not in women (OR = 1.17, 95% CI 0.31-4.47). Exposure to leather dust was associated with an excess risk in both genders. Both wood and leather dust were associated with adenocarcinomas rather than squamous cell carcinomas. Excess risks for smoking were higher for squamous cell carcinomas and higher in men than in women. CONCLUSIONS: In these European populations, occupation was associated with about 11% of all sinonasal cancers in women and 39% in men. This difference can, in part, be attributed to variation in exposure patterns between genders

BACKGROUND: The prostate-specific antigen test was approved by the U.S. Food and Drug Administration in 1986 to monitor the disease status in patients with prostate cancer and, in 1994, to aid in prostate cancer detection. However, after 1986, the test was performed on many men who had not been previously diagnosed with prostate cancer, apparently resulting in the diagnosis of a substantial number of early tumors. Our purpose is to provide insight into the effect of screening on prostate cancer rates. Detailed data are presented for whites because the size of the population allows for calculating statistically reliable rates; however, similar overall trends are seen for African-Americans and other races. METHODS: Prostate cancer incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and mortality data from the National Center for Health Statistics were analyzed. RESULTS/CONCLUSIONS: The following findings are consistent with a screening effect: 1) the recent decrease since 1991 in the incidence of distant stage disease, after not having been perturbed by screening; 2) the decline in the incidence of earlier stage disease beginning the following year (i.e., 1992); 3) the recent increases and decreases in prostate cancer incidence and mortality by age that appear to indicate a calendar period effect; and 4) trends in the incidence of distant stage disease by tumor grade and trends in the survival of patients with distant stage disease by calendar year that provide suggestive evidence of the tendency of screening to detect slower growing tumors. IMPLICATIONS: The decline in the incidence of distant stage disease holds the promise that testing for prostate-specific antigen may lead to a sustained decline in prostate cancer mortality. However, population data are complex, and it is difficult to confidently attribute relatively small changes in mortality to any one cause

BACKGROUND: In the U.S., the incidence rate of multiple myeloma is more than twice as high for blacks as for whites, but the etiology of this malignancy is not well understood. METHODS: A population-based case-control interview study of 565 subjects (361 white, 204 black) with multiple myeloma and 2104 controls (1150 white, 954 black) living in 3 areas of the U.S. offered the opportunity to explore whether family history, of cancer contributes to the risk of multiple myeloma and explains the racial disparity in risk. RESULTS: For both races combined, the risk of multiple myeloma was significantly elevated for subjects who reported that a first-degree relative had multiple myeloma (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2-12.0). Increased risk was also associated with a family history of any hematolymphoproliferative (HLP) cancer (OR = 1.7, 95% CI = 1.0-2.8), especially in a sibling (OR = 2.3, 95% CI = 1.1-4.5). The risk associated with familial occurrence of HLP cancer was higher for blacks than for whites, but the difference between the ORs was not statistically significant. CONCLUSIONS: These data are consistent with previous studies that indicate a familial risk of multiple myeloma, but they explain little of the race-related difference in incidence rates

OBJECTIVES: To determine risk for oral cancer in Puerto Rico associated with use of alcohol and tobacco. METHODS: In Puerto Rico, alcohol and tobacco use were compared among nonsalivary gland cancers of the mouth and pharynx (n = 342), cancers of major and minor salivary glands (n = 25) and 521 population-based controls. RESULTS: Alcohol (usual use, Ptrend < 0.0001 for men and Ptrend = 0.02 for women) and tobacco (usual use, Ptrend < 0.0001, for both men and women) were strong independent risk factors for oral cancer in Puerto Rico, with a multiplicative effect from combined exposures. Risks did not vary systematically by use of filter vs. nonfilter cigarettes. Risks with use of other forms of smoked tobacco were about sevenfold among both men and women. Risks decreased only gradually after cessation of tobacco and alcohol use. Tobacco use, but not alcohol, was linked to cancers of the salivary glands. The burden of oral cancer due to alcohol and tobacco use in Puerto Rico (76% for men, 52% for women) agreed closely with earlier estimates for the mainland US population, while about 72% of salivary gland cancer (men and women, combined) was due to tobacco use. CONCLUSIONS: Excess risks for oral cancer in Puerto Rico are largely explained by patterns of alcohol and tobacco use. Smoking filter vs. nonfilter cigarettes does not alter risk, while cessation of alcohol and tobacco use appears to reduce risk only gradually