Conflicts between two cultures: implications for epidemiologic researchers in communicating with policy-makers.
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Biomedical subjects
Publications and source records attributed to G M Matanoski.
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A population from a hearing clinic in Washington County, Maryland, in 1943-1960 was followed to assess the risk of developing neoplasms from radium treatment of the nasopharynx for adenoid hypertrophy. Of the 2,925 subjects who attended the clinic, 904 received radium treatment. A nonconcurrent prospective study compared the cancer incidence among the irradiated persons with that among persons with other treatments. Seven brain tumor cases (three malignant and four benign) were identified in the irradiated group versus none in the nonirradiated group (relative risk = 14.8, 95% confidence interval: 0.76, 286.3). A nonsignificant excess risk of thyroid cancer was detected in the irradiated group based on two cases in the exposed group and one case in the nonexposed group (relative risk = 4.2, 95% confidence interval: 0.38, 46.6). Decreased risks of breast cancer, female genital cancers, and prostate cancer were observed among the irradiated individuals, although these deficits were not statistically significant individually. The decreased risk of sex hormone-related cancers in the irradiated group suggests possible radiation damage to the pituitary, with consequent reduction in pituitary hormone output and alterations in sexual and other hormonal development in early life. This hypothesis needs further evaluation.
Disinfection by-products (DBP) are a side effect of water chlorination. Some toxicological studies suggest an association between DBP exposure and adverse reproductive and developmental effects. This investigation considered all toxicological and epidemiological evidence for the various effects, outcome by outcome. The weight of evidence demonstrated that no association with DBP exposure exists for over a dozen outcomes including low and very low birth weight, preterm delivery, some specific congenital anomalies, and neonatal death. The analysis found inconsistent or very weak results for all congenital anomalies/birth defects, all central nervous system anomalies, neural tube defects, spontaneous abortion, and stillbirth. The weight of evidence suggested a positive association with DBP exposure for some measure of growth retardation (such as intrauterine growth retardation or small for gestational age) and for urinary tract anomalies. Having catalogued these effects, it should be noted that exposure assessment in the epidemiological studies published to date has been inadequate to definitively demonstrate an association of small magnitude. Exposure to DBP primarily has been based on routine (i.e., quarterly) monitoring of public water supplies for trihalomethanes (THM) matched to maternal residence. In order to determine whether an association exists between adverse reproductive and developmental effects and exposure to DBP, studies must consider the THM concentration and the quantity of the water actually consumed by pregnant women.
Carbonless copy paper (CCP), introduced in 1954, is ubiquitous in the U.S. marketplace, and because of this, many workers come into contact with it. Its safety to workers who handle large amounts of CCP has been addressed in numerous studies and reports; and the National Institute for Occupational Safety and Health (NIOSH) on two occasions has sought to determine what, if any, hazards to health CCP might pose. This review encompasses the world's literature on CCP and provides a weight-of-evidence analysis of the safety of CCP to workers in the United States. CCP is systematically studied on large groups of humans using repeat insult patch tests. Consistently, CCP in U.S. commerce since 1987 (the focus of this review) has produced neither primary skin irritation nor skin sensitization under exaggerated test conditions, demonstrating that no irritation or sensitization is expected on contact with CCP under normal conditions of manufacture and use. Years after the introduction of CCP, the first case reports appeared in 1974 suggesting an association between CCP use and various generic symptoms. Most of the earliest reports occurred in Sweden in response to negative publicity concerning the product, and to date approximately half of all published articles originate in Scandinavia. Many early reports were questionnaire/interview studies which suffered from suggestive questions, biases, and lack of control for confounding factors. Few studies included a comparison group (i.e., people not exposed to CCP) making it impossible to estimate risk values. Later, sick building syndrome studies, accounting for many relevant factors in the office environment, found no association between CCP exposure and symptoms unexplained by other factors. Animal studies showed that compounds used to manufacture CCP do not have acute toxic potential and are not genotoxic. Finally, very few published complaints have come from the manufacturing sector where the closest and most voluminous contact occurs. A few reports of symptoms have emanated from printing facilities (with a multiplicity of other chemical exposures), but generally most symptoms are reported in the office setting where the exposure is lower than in the manufacturing or printing settings. Based on the weight of the evidence, CCP currently in commerce in the United States is shown not to be the causative agent for the reported general symptoms sometimes associated with it over the years. Recently NIOSH evaluated the literature as to possible hazards to health posed by CCP, and NIOSH is anticipated to conclude that CCP is not a hazard to workers and has only a small possibility of producing mild and transient skin irritation.
Drinking mutagenic downstream water from the Huangpu River was hypothesized to have increased the risk for male esophageal cancer in Shanghai, China. The authors conducted a population-based case-control study of a total of 71 esophageal cancer deaths and 1,122 controls collected during a 5-year follow-up period, 1984-1988, from four male cohorts born before January 1, 1944, living in four communities consuming water with different mutagenicities in the Shanghai area. The controls represented a 1% random sample of the defined living cohorts selected at the end of each of the 5 years of follow-up. Logistic regression showed an odds ratio of 2.77 (95% confidence interval: 1.52, 5.03) for drinking mutagenic downstream water from the river versus drinking nonmutagenic upstream water after controlling for possible confounders including age, disease history (hepatitis, cirrhosis, schistosomiasis, digestive tract ulcer), hazardous occupational history, pesticide exposure, lifestyle factors (cigarette smoking, tea intake, and alcohol intake), dietary habits (intake of pickled vegetables, maize, peanuts, and cured meat), education, poverty, urban environment, and water chlorination.
A study of pulp and paper mill workers indicated low risks of death from all causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81) compared with U.S. rates. The leukemia death rate in workers was not higher than the U.S. rate but was higher than the rate in county populations surrounding mills. Workers whose last jobs were in the finishing areas of the mills had an elevated SMR for liver cancer. An internal comparison of occupational characteristics indicated that workers employed in mills using other chemical pulping operations had significantly elevated mortality from all causes, all cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was elevated in mills using kraft pulping. The internal comparisons confirmed the association between work in finishing and the risk of liver cancer. This study was designed to investigate whether pulp and paper mill workers have any risks that would indicate the need for studies detailing exposures.
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In 1978 an epidemiologic study exploring the health consequences of nasopharyngeal radium irradiation among individuals treated for adenoid enlargement in Washington County, Maryland, found an excess risk of brain tumors and a deficit of female breast cancers. The study population included all persons first seen at the Washington County Clinic for the Prevention of Deafness in Children from 1940 to January 1, 1960. We will continue the follow-up of irradiated and nonirradiated patients to (1) assess the risk of brain tumors and other neoplasms of the head and neck developing during a 40-year period, (2) assess hormone-related disorders resulting from irradiation of the pituitary gland, and (3) compare cancer incidence and mortality rates among exposed and nonexposed groups. Of the 2135 persons eligible for this study, 93.5% have been traced, and 90% have replied to a mailed questionnaire that elicits information on demographic characteristics, reproductive and medical history, infertility, and other sources of radiation exposure. Information on cancer incidence and mortality is being obtained from the Washington County Cancer Registry and death certificate files from Washington County and the Social Security Administration. Statistical methods to be used in the data analysis include standardized mortality ratios, standardized cancer incidence ratios, and Kaplan-Meier survival analysis.
Workers in abattoirs and meatpacking plants have potential for exposure to bovine leukemia virus (BLV) and bovine papilloma viruses (BPV), which are oncogenic in cattle. These workers also have increased exposure to human papilloma viruses (HPV) and certain chemical carcinogens. We investigated whether such a group showed increased risk of cancers. We report mortality results after an additional 9-year follow-up of a previously studied group of 5,522 workers in abattoirs and 4,589 workers in meatpacking plants. Excess risk of all cancers combined, cancers of the lung, buccal cavity and pharynx, esophagus, colon, bladder, kidney, and bone was observed. Since factors such as tobacco smoking, alcohol, and diet, which have known associations with some of these cancers, were not taken into account, the significance of these findings is not known, except for lung cancer, for which occupational factors are probably involved. Because some of these findings have been consistently reported before, studies that will control for confounding factors as well are now urgently needed.
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Sunlight exposure and certain host factors such as red hair and fair skin are established risk factors for non-melanoma skin cancers. Because deficient DNA repair capacity has contributed to the development of skin cancers in a rare genetic disease, xeroderma pigmentosum, we explored this deficiency as an etiologic factor in a recent population study. We used a new DNA repair assay, the host-cell reactivation, in a clinic-based case-control study to test the hypothesis that reduced DNA repair is the underlying molecular mechanism for the development of sunlight-induced basal cell carcinoma. The peripheral lymphocytes from 88 patients with primary BCC and 135 cancer-free controls were tested for their capacity to repair ultraviolet light-induced DNA damage in a reporter gene, chloramphenicol acetyl transferase. All subjects were between the ages of 20 and 60 years and were frequency matched by age (+/- 5) and sex. Among those who reported frequent sunbathing, poor tanning ability, a history of multiple sunburns, exposure to chemicals, or multiple medical irradiations, the BCC patients had significantly lower DNA repair capacity than controls (p < 0.05). DNA repair capacity was also found substantially lower in the basal cell carcinoma patients who had red hair and light skin (type I). Compared to controls, basal cell carcinoma cases with selected risk factors had a relative decrease in DNA repair capacity of 10-28%. These findings provided evidence that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.
This study investigated the role of DNA repair in susceptibility to sunlight-induced basal cell carcinoma using a host cell reactivation assay in peripheral lymphocytes. The study included Maryland basal cell carcinoma patients and cancer-free dermatologic controls who had had noncancerous skin disorders diagnosed between 1987 and 1990. Logistic regression models were used to assess the independent effect of the selected variables stratified by DNA repair level, with adjustment for age and family history. Skin type, lifetime number of severe sunburns, and actinic elastosis were also selected as risk factors for basal cell carcinoma. Cryopreserved lymphocytes from 88 cases and 135 controls were used for the DNA repair assay. When data were stratified by DNA repair level and adjusted for age and family history of skin cancer, significantly increased odds ratios associated with lighter skin (odds ratio (OR) = 3.2, 95% confidence interval (CI) 1.5-7.3), six or more severe sunburns in a lifetime (OR = 4.2, 95% CI 1.6-10.7), and moderate or severe actinic elastosis (OR = 4.4, 95% CI 1.5-12.8) were observed in persons with low DNA repair but not in those with high DNA repair. These findings suggest that impaired DNA repair may be a susceptibility factor for sunlight-induced skin cancer in the general public, as it is in patients with xeroderma pigmentosum.
Defective repair of sunlight-induced DNA photodamage, coupled with an unusually high occurrence of multiple primary basal cell carcinomas (BCCs), is the major characteristic of xeroderma pigmentosum. Our recent work has indicated that this etiological paradigm may apply to skin cancer patients without an apparent hereditary disease. The present study reports on an investigation of whether medications such as photosensitizing drugs (antibiotics, corticosteroids, and aspirin) modulate skin cancer risk through alterations in DNA repair capacity (DRC). Using a new DNA repair (host cell reactivation) assay with peripheral T-lymphocytes, we tested DRCs of 88 Caucasian BCC patients and 135 cancer-free controls. Subjects were between 20 and 60 years of age and free of known hereditary skin diseases. The age-adjusted means of DRC were calculated to compare repair levels associated with the use of specific drugs and hormones. Multiple linear regression models were used to correlate DRC with the number of skin cancers. The estimated odds ratio was used to describe the risk of BCCs. The distribution of DRCs of subjects was approximately normal, with a 5-fold variation between individuals. DRCs below the upper 30th percentile of controls were associated with an estimated 2.3-fold (95% confidence interval, 1.17-4.54-fold) increased risk for the occurrence of BCCs. The lower the DRC was, the greater the number of skin tumors in individuals (P < 0.05), after adjustment for age. Although supplemental vitamin use was associated with reduced risk of skin cancer, it was not associated with differences in subjects' DRCs. However, individuals who reported taking either tetracycline or estrogen, two photosensitizing drugs, had higher DRCs, compared with those who had not used these drugs. Low DRC or a family history of skin cancer increased the probability that patients who were overexposed to sunlight would have multiple BCCs. DNA repair levels may be influenced by the use of selected photosensitizing drugs and estrogen.
The purpose of this paper is to present the assessment of magnetic field exposure conducted as a part of a nested case-control investigation of leukemia mortality in telephone lineworkers. For the purposes of exposure classification, telephone company jobs were initially divided into two classes: those with potential for working in an electric environment, referred to as linework jobs, and those not working in an electric environment, referred to as nonlinework jobs. Linework jobs were further divided into the following four categories: outside plant technicians (OPT), installation/maintenance/repair (IMR) technicians, central office technicians (COT), and cable splicing technicians (CST). These job groupings were based on similarity of work tasks and exposure environments. Emdex data-logging dosimeters were used to measure personal exposures to ELF magnetic fields for 204 telephone company workers. Three general classes of exposure indices were calculated for each exposure record: measures of central tendency, measures of peak or maximum exposure, and measures of exposure variability. CSTs had the highest full-shift mean and median exposure, 4.3 and 3.2 mG, respectively. CSTs also ranked the highest, with average peak, average 95th percentile, and average time above background equal to 99.2 mG, 11.1 mG, and 156 min, respectively. In addition, the results suggest the OPT and IMR technicians have exposures similar to nonlineworkers. Exposure classifications, therefore, which misclassify all lineworkers into one "telephone lineworker" job grouping are not appropriate and future studies should concentrate on cable splicing technicians.
A clinic-based case-control study was conducted to determine the association between vitamin supplement use and risk of basal cell carcinoma (BCC) of the skin. The subjects were 131 patients with histopathologically confirmed primary BCC and 200 cancer-free controls with non-premalignant skin disorders. Use of any vitamins (mainly multivitamins and vitamins A, C, and E) was associated with reduced risk of BCC. After controlling for age, sex, cigarette smoking, number of lifetime severe sunburns, and skin actinic elastosis, regular vitamin supplementation was associated with a significantly reduced risk of BCC (odds ratio (OR) = 0.3; 95% confidence interval (CI) = 0.2-0.06). The ORs decreased as the regularity (p < 0.001) and daily doses of supplement used increased, especially for vitamins A (p < 0.005) and E (p < 0.005). Vitamin supplementation was not associated with alterations in cellular DNA repair. These results, however, cannot be considered conclusive because of the relatively low participation rates (131/830 for cases and 200/1406 for controls) due to the requirement of blood donation and more rigorous studies are needed to clarify the effect of supplemental vitamins, particularly of vitamins A and E, on the risk of BCC of the skin.
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