Search

Tetrafluoroethylene (TFE), a compound used for the production of fluorinated polymers including polytetrafluoroethylene, increases the incidence of liver and kidney cancers and leukemia in rats and mice. This is the first time the cancer risk in humans has been explored comprehensively in a cohort mortality study (1950-2008) that included all polytetrafluoroethylene production sites in Europe and North America at the time it was initiated. A job-exposure matrix (1950-2002) was developed for TFE and ammonium perfluoro-octanoate, a chemical used in the polymerization process. National reference rates were used to calculate standardized mortality ratios (SMRs) and 95% confidence intervals. Among 4,773 workers ever exposed to TFE, we found a lower rate of death from most causes, as well as increased risks for cancer of the liver (SMR = 1.27; 95% confidence interval: 0.55, 2.51; 8 deaths) and kidney (SMR = 1.44; 95% confidence interval: 0.69, 2.65; 10 deaths) and for leukemia (SMR = 1.48; 95% confidence interval: 0.77, 2.59; 12 deaths). A nonsignificant upward trend (P = 0.24) by cumulative exposure to TFE was observed for liver cancer. TFE and ammonium perfluoro-octanoate exposures were highly correlated, and therefore their separate effects could not be disentangled. This pattern of findings narrows the range of uncertainty on potential TFE carcinogenicity but cannot conclusively confirm or refute the hypothesis that TFE is carcinogenic to humans.

Worldwide lung cancer incidence is decreasing or leveling off among men, but rising among women. Sex differences in associations of tobacco carcinogens with lung cancer risk have been hypothesized, but the epidemiologic evidence is conflicting. We tested sex-smoking interaction in association with lung cancer risk within a population-based case-control study, the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study (Lombardy, Italy, 2002-2005). Detailed lifetime smoking histories were collected by personal interview in 2,100 cases with incident lung cancer and 2,120 controls. Odds ratios and 95% confidence intervals for pack-years of cigarette smoking were estimated by logistic regression, adjusted for age, residence area, and time since quitting smoking. To assess sex-smoking interaction, we compared the slopes of odds ratios for logarithm of pack-years in a model for men and women combined. Overall, the slope for pack-years was steeper in men (odds ratio for female-smoking interaction = 0.39, 95% confidence interval: 0.24, 0.62; P < 0.0001); after restriction to ever smokers, the difference in slopes was much smaller (odds ratio for interaction = 0.63, 95% confidence interval: 0.29, 1.37; P = 0.24). Similar results were found by histological type. Results were unchanged when additional confounders were evaluated (e.g., tobacco type, inhalation depth, Fagerstrom-assessed nicotine dependence). These findings do not support a higher female susceptibility to tobacco-related lung cancer.

Since the year 2000, evaluation of the impact of air pollution on people's health has drawn the attention of the general public and has led decision-makers to develop specific health policies. In most of the health impact assessment literature, investigators have reported on long- and short-term effects of air pollution. Here the authors present results of a health impact assessment of short-term effects of particulate matter ≤10 μm in diameter (PM(10)) in the Lombardy region of Italy (2003-2006). The impact was evaluated in terms of numbers of attributable deaths under several counterfactual scenarios of air pollution reduction based on World Health Organization guidelines and European Union limits. The authors found that annual average PM(10) levels exceeding the World Health Organization threshold of 20 μg/m(3) and the European Union limit of 40 μg/m(3) were responsible for 302 and 109 attributable deaths per year, corresponding to attributable community rates of 13 and 5 deaths per 100,000 inhabitants per year, respectively. A 20% reduction in existing PM(10) levels could reduce by more than 30% the burden of short-term deaths linked to ambient air pollution. Therefore, policies for air pollution reduction appear to be necessary in order to protect and improve individual and community health.

The authors investigated the relation between alcohol consumption and lung cancer risk in the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study, a population-based case-control study. Between 2002 and 2005, 2,100 patients with primary lung cancer were recruited from 13 hospitals within the Lombardy region of Italy and were frequency-matched on sex, area of residence, and age to 2,120 randomly selected controls. Alcohol consumption during adulthood was assessed in 1,855 cases and 2,065 controls. Data on lifetime tobacco smoking, diet, education, and anthropometric measures were collected. Adjusted odds ratios and 95% confidence intervals for categories of mean daily ethanol intake were calculated using unconditional logistic regression. Overall, both nondrinkers (odds ratio = 1.42, 95% confidence interval: 1.03, 2.01) and very heavy drinkers (>/=60 g/day; odds ratio = 1.44, 95% confidence interval: 1.01, 2.07) were at significantly greater risk than very light drinkers (0.1-4.9 g/day). The alcohol effect was modified by smoking behavior, with no excess risk being observed in never smokers. In summary, heavy alcohol consumption was a risk factor for lung cancer among smokers in this study. Although residual confounding by tobacco smoking cannot be ruled out, this finding may reflect interplay between alcohol and smoking, emphasizing the need for preventive measures.

Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.

Received for publication February 6, 2001, and accepted for publication February 21, 2001. Abbreviation: TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1 Department of Occupational and Environmental Health, EPOCA, Research Center for Occupational, Clinical and Environmental Epidemiology, University of Milan, Milan, Italy. 2 Unit of Epidemiology, Department of Occupational Health and Safety, Istituti Clinici di Perfezionamento, Milan, Italy. 3 Regional Epidemiological Office, Health Directorate, Regione Lombardia, Milan, Italy. Reprint requests to Dr. Pier Alberto Bertazzi, EPOCA, Epidemiology Research Center, Department of Occupational and Environmental Health, University of Milan, 8 Via San Barnaba, 20122 Milano, Italy (e-mail: pieralberto.bertazzi@unimi.it). We thank Smith and Lopipero for their invited commentary (1), which we found appropriate and useful for interpreting the latest Seveso, Italy, findings (2). Human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is widespread (3). Epidemiologic studies are essential to assessing the risk linked to the environmental contamination, and consistency in the findings enhances confidence in their results. It is not surprising that, on average, exposure to TCDD in Seveso was lower than in occupational cohorts. In the former case, the chemical release was limited in time, and its content eventually was diluted over an extended outdoor area (4). Still, the average TCDD blood concentration in the Seveso population was two orders of magnitude higher than the reported background environmental level (1). Thus, the finding of increased cancer mortality cannot be considered totally unexpected. An increase in all-cancer and lung cancer mortality, consistent with what was observed in occupational cohorts, was found in men in zones A and B after 15 years. Smith and Lopipero (1) suggest that smoking might be the actual explanation. This is a possibility, and we intend to further explore smoking habits in our index and referent populations. However, if the increased risk was due to smoking, one would expect high rate ratios for the whole study period, not only 15–20 years since dioxin exposure. With regard to concomitant potentially smoking-related findings, several other studies linked increased cardiovascular mortality to dioxin exposure, sometimes with a dose-related pattern (5–7) and use of internal reference groups (6, 7), thus leaving little room for confounding arguments. In addition, other smoking-related cancers (e.g., larynx, esophagus, pancreas, and bladder) were not elevated in Seveso males after 15 years (2). To be a confounder, smoking should be distributed unevenly among zones. Independent surveys assessed smoking habits in 1986–1987 in random samples of the population of Desio (352 subjects), one of the cities affected by the Seveso accident, and in the population in a nearby district outside the study area (466 subjects), quite similar to our reference population. Distribution of the subjects by smoking category in the two samples was as follows: never smokers, 76 (22 percent) in Desio versus 104 (22 percent) in the outside area; former smokers, 107 (30 percent) versus 154 (33 percent); current smokers of 20 cigarettes/day, 40 (11 percent) versus 36 (8 percent) (8).This, although limited, set of data suggests that geographic variation in smoking habits might be negligible across subareas in the region including the accidentally contaminated territory. Although we admit that with so many data “there is a little bit of something for everybody” (1, p. 1046), results for lymphatic and hemopoietic neoplasms clearly do stand out. The pattern suggests a systematic difference in mortality from these causes between the TCDD-exposed and the local reference population. Cancer incidence data for the first postaccident period support these findings (9). The nonHodgkin’s lymphoma increase became significant after 15 years (five observed; rate ratio 2.8, 95 percent confidence interval: 1,1, 7.0). An increased occurrence of nonHodgkin’s lymphoma also has been observed in occupational cohorts (6, 10, 11). On the basis of our interpretation, the 20-year mortality results do show that the Seveso population experienced, consistent with other exposed populations, a modest excess of all-cancer and respiratory cancer mortality long after initial exposure and a moderately increased occurrence of lymphatic and hematopoietic cancer. This pattern is different from what might have been expected on the basis of animal experiments. A limited number of persons probably had extremely high levels of exposure, and susceptibility factors might also have played a role.