- Email: [email protected]
Methods for testing interactions, with applications to occupational exposure, smoking, and lung cancer
Lung
Cancer,
5 (1989) Sl-S42
Sl
Elsevier
ABSTRACTS Prevention Natural history of adenocarcinoma - large cell carcinoma of the lung: Conclusions from screening programs in New York and Baltimore. Flehinger BJ, Kimmel M, Melamed MR. Mathematical Sciences Deparlmenl, IBh4Research Division. Thomas J. Watson Research Center, Yorktown Heights, NY 10598. J Nat1 Cancer Inst 1988;80: 337-44. A mathematical model of the progression kinetics of lung cancer was described and used to shed light on the natural history of adenocarcinomaand largecell carcinomaof lung from datacollected in screening studies of male smokers by the Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Medical Institutions. In both programs, estimates of the mean duration of early-stage adenocarcinoma or large cell carcinomaof lung ranged upward from 4 years, and estimates of the probability of detecting it in early-stage disease ranged downward from .16.The probabilities of curing early-stage disease through surgical treatment were found to be at most .52 and .13 in the New York and Baltimore studies, respectively. These estimates led to the conclusion thatexpectedreduction in mortality from adenocarcinomaandlargecell carcinoma of lung as due to annual X-ray screening from age 45 to 80 years is not greater than 18% in New York and 5% in Baltimore.
Vitamin A and female lung cancer: A case-control study on plasma and diet. Pastorino U, Pisani P, Berrino Fetal. Thoracic Oncology Deparrmenf, lsiitulo Nazionale Tumori, Milan. Nutr Cancer 1987;10:171- 9. Plasma and dietary levels of retinal and O-carotene were evaluated in a consecutive series of 47 females with histologically proven primary lung cancer and 159 nonneoplastic controls. The dietary questionnaire included 69 different items: special care was given to foods rich in vitamin A and seasonal foods (e.g., vegetables and fruits), whereas serum analysis was focused on retinol and B-carotene. Age-adjusted mean values for cases and controls were, respectively, 458.3 VS. 551.3 mg forplasmaretinol, 276.1 vs. 390.1 mg forplasmacarotene; 598.1 vs. 820.6 mg for daily retinol, and 628.0 vs. 882.5 mg for dietary carotene. Theoddsratios for low vs. high tertile, adjusted forage, smoking,retinol or carotene, cholesterol,and triglycerides by multivariate analysis were, respectively, 1.13 for plasma retinol, 5.04 for plasma carotene, 3.27 for dietary retinol,and2.93 fordietarycarotene. Forall theexamined items, there was a trend of increased risk for the second and third tertile, and statistical significance was reached for plasma O-carotene (p < 0.05). Thehypothesistbata higherriskoflungcancerisrelatedtoalowvitamin A consumption
is supported by these data.
Epidemiology Biologic interactions between smokingand occupational exposures. Burns DM, Froines JR, Jarvik ME. Division of Pulmonary and Crifical Care Medicine, UCSD Medical Center, San Diego, CA 92103. Am J Ind Med 1988;13: 169-79. Cigarette smoking is a major cause of cancer and lung disease in the U.S. population. The biological processes that underlie the response of the lung to cigarette smoke are important considerations for designing analyses of the effects of occupational exposures. Interactions between cigarette smoking and occupational exposures may occur through a combined effect on the mechanism of disease production, through an effect on the dose of the toxic substances that reach the target issue, or through an effect on the response of the lung to the toxic agents. Disease due to occupational exposures can occur in a similar pattern in both smokers and nonsmokers; however, as more complex interactions are examined, different responses to the same occupational exposure may be identified for smokers and nonsmokers. It is only through the successful intermingling of biologic information with epidemiologic data that these interactions can bc fully examined.
Methods for testing interactions, with applications to occupational exposures, smoking, and lung cancer. Thomas DC, Whittemore AS. Deparfment of Preventive Medicine, University of Soulhern Califarnia, Los Angeles, CA 90033. Am J Ind Med 1988;13:131-47. Various approaches to assessing the interaction between smoking and occupational exposures are described. The definition of interaction depends on the measure of association under consideration and can be expressed in terms of disease risk, time, or dose. Simple descriptive methods and maximum likelihood model fitting methods are presented for analyzing interaction in terms of joint effects on disease risk. Methods for assessing the influence of exposures on times to disease, using appropriate denominators, are also described. The various approaches are illustrated with published data on lung cancer in relation to asbestos, radon daughters, cbloromethyl ethers, and arsenic. Some of tbc mechanisms that can be invoked to explain the observed patterns include initiation and promotion, lung clearance, transport across cell membranes, and mucous secretion. 0169-5002/89/$
03.50 @ 1989 Elsevier Science Publishers
and Etiology
Reanalysis of lung cancer mortality in a National Cancer Institute study on mortality among industrial workers exposed to formaldehyde. Sterling TD, Weir&am JJ. Faculry of Applied Sciences, School of Computing Science, Simon Fraser University. Burnaby. BC V5A IS6 J Occep Med 1988:30:895-901. The results of an historical cohort study of mortality among individuals occupationally exposed to formaldehyde were announced in 1986 by BlairetaJ (JNCI 1986; 76: 1071-1084). The study was ajointunde.rtaking of the National Cancer Institute and the Formaldehyde Institute, and concluded, ‘...thislarge multiplantcohortstudyprovidedlitdeevidence to suggest that formaldehyde exposures affected the mortality experience of these industrial workers.’ However, there were concerns by a number of workers that the design and analysis of the study had possibly masked an existing occupational hazard. Analyzing time-integrated exposure to formaldehyde without simultaneously considering length of exposure and comparing mortality of formaldehyde workers to mortality of the general population could have masked an increase in cancer risksbecauseof the healthy workereffect. Acopyoftbedataofthestudy was obtained from the principal investigator and reanalyzed. We find a significantly increased risk for all cancers and for lung cancer as a function of cumulative exposure when workers with higher levels of exposure are compared with those with little or no exposure while simultaneouslyconsideringlenghtofexposure.Whentheriskratio(RR) for lung cancer at _ 0. I ppm cumulative exposure (CX) is taken as 1.O, the lung cancer RR for CX of 0.1 to 0.5 ppm is 1.4 1 (1.20 to 1.66), the RRforCXof0.5to2.0ppmisl.73(1.42to2.11),andtheRRforCX _ 2.0 is I .70 (1.32 to 2.18). Hourly workers have a significantly higher RR than salaried workers (RR = 1.58). Similar increased RRs are observed for all cancers and all causes. The RRs for different length of exposure are not significantly elevated because of the mathematical relationship betweencumulativeexposure,lengtbofexposure,andlevel of exposure and because of the possibility that workers exposed to very high levels of exposure may tend to leave employment early.
B.V. (Biomedical
Division)
Cancer,
5 (1989) Sl-S42
Sl
Elsevier
ABSTRACTS Prevention Natural history of adenocarcinoma - large cell carcinoma of the lung: Conclusions from screening programs in New York and Baltimore. Flehinger BJ, Kimmel M, Melamed MR. Mathematical Sciences Deparlmenl, IBh4Research Division. Thomas J. Watson Research Center, Yorktown Heights, NY 10598. J Nat1 Cancer Inst 1988;80: 337-44. A mathematical model of the progression kinetics of lung cancer was described and used to shed light on the natural history of adenocarcinomaand largecell carcinomaof lung from datacollected in screening studies of male smokers by the Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Medical Institutions. In both programs, estimates of the mean duration of early-stage adenocarcinoma or large cell carcinomaof lung ranged upward from 4 years, and estimates of the probability of detecting it in early-stage disease ranged downward from .16.The probabilities of curing early-stage disease through surgical treatment were found to be at most .52 and .13 in the New York and Baltimore studies, respectively. These estimates led to the conclusion thatexpectedreduction in mortality from adenocarcinomaandlargecell carcinoma of lung as due to annual X-ray screening from age 45 to 80 years is not greater than 18% in New York and 5% in Baltimore.
Vitamin A and female lung cancer: A case-control study on plasma and diet. Pastorino U, Pisani P, Berrino Fetal. Thoracic Oncology Deparrmenf, lsiitulo Nazionale Tumori, Milan. Nutr Cancer 1987;10:171- 9. Plasma and dietary levels of retinal and O-carotene were evaluated in a consecutive series of 47 females with histologically proven primary lung cancer and 159 nonneoplastic controls. The dietary questionnaire included 69 different items: special care was given to foods rich in vitamin A and seasonal foods (e.g., vegetables and fruits), whereas serum analysis was focused on retinol and B-carotene. Age-adjusted mean values for cases and controls were, respectively, 458.3 VS. 551.3 mg forplasmaretinol, 276.1 vs. 390.1 mg forplasmacarotene; 598.1 vs. 820.6 mg for daily retinol, and 628.0 vs. 882.5 mg for dietary carotene. Theoddsratios for low vs. high tertile, adjusted forage, smoking,retinol or carotene, cholesterol,and triglycerides by multivariate analysis were, respectively, 1.13 for plasma retinol, 5.04 for plasma carotene, 3.27 for dietary retinol,and2.93 fordietarycarotene. Forall theexamined items, there was a trend of increased risk for the second and third tertile, and statistical significance was reached for plasma O-carotene (p < 0.05). Thehypothesistbata higherriskoflungcancerisrelatedtoalowvitamin A consumption
is supported by these data.
Epidemiology Biologic interactions between smokingand occupational exposures. Burns DM, Froines JR, Jarvik ME. Division of Pulmonary and Crifical Care Medicine, UCSD Medical Center, San Diego, CA 92103. Am J Ind Med 1988;13: 169-79. Cigarette smoking is a major cause of cancer and lung disease in the U.S. population. The biological processes that underlie the response of the lung to cigarette smoke are important considerations for designing analyses of the effects of occupational exposures. Interactions between cigarette smoking and occupational exposures may occur through a combined effect on the mechanism of disease production, through an effect on the dose of the toxic substances that reach the target issue, or through an effect on the response of the lung to the toxic agents. Disease due to occupational exposures can occur in a similar pattern in both smokers and nonsmokers; however, as more complex interactions are examined, different responses to the same occupational exposure may be identified for smokers and nonsmokers. It is only through the successful intermingling of biologic information with epidemiologic data that these interactions can bc fully examined.
Methods for testing interactions, with applications to occupational exposures, smoking, and lung cancer. Thomas DC, Whittemore AS. Deparfment of Preventive Medicine, University of Soulhern Califarnia, Los Angeles, CA 90033. Am J Ind Med 1988;13:131-47. Various approaches to assessing the interaction between smoking and occupational exposures are described. The definition of interaction depends on the measure of association under consideration and can be expressed in terms of disease risk, time, or dose. Simple descriptive methods and maximum likelihood model fitting methods are presented for analyzing interaction in terms of joint effects on disease risk. Methods for assessing the influence of exposures on times to disease, using appropriate denominators, are also described. The various approaches are illustrated with published data on lung cancer in relation to asbestos, radon daughters, cbloromethyl ethers, and arsenic. Some of tbc mechanisms that can be invoked to explain the observed patterns include initiation and promotion, lung clearance, transport across cell membranes, and mucous secretion. 0169-5002/89/$
03.50 @ 1989 Elsevier Science Publishers
and Etiology
Reanalysis of lung cancer mortality in a National Cancer Institute study on mortality among industrial workers exposed to formaldehyde. Sterling TD, Weir&am JJ. Faculry of Applied Sciences, School of Computing Science, Simon Fraser University. Burnaby. BC V5A IS6 J Occep Med 1988:30:895-901. The results of an historical cohort study of mortality among individuals occupationally exposed to formaldehyde were announced in 1986 by BlairetaJ (JNCI 1986; 76: 1071-1084). The study was ajointunde.rtaking of the National Cancer Institute and the Formaldehyde Institute, and concluded, ‘...thislarge multiplantcohortstudyprovidedlitdeevidence to suggest that formaldehyde exposures affected the mortality experience of these industrial workers.’ However, there were concerns by a number of workers that the design and analysis of the study had possibly masked an existing occupational hazard. Analyzing time-integrated exposure to formaldehyde without simultaneously considering length of exposure and comparing mortality of formaldehyde workers to mortality of the general population could have masked an increase in cancer risksbecauseof the healthy workereffect. Acopyoftbedataofthestudy was obtained from the principal investigator and reanalyzed. We find a significantly increased risk for all cancers and for lung cancer as a function of cumulative exposure when workers with higher levels of exposure are compared with those with little or no exposure while simultaneouslyconsideringlenghtofexposure.Whentheriskratio(RR) for lung cancer at _ 0. I ppm cumulative exposure (CX) is taken as 1.O, the lung cancer RR for CX of 0.1 to 0.5 ppm is 1.4 1 (1.20 to 1.66), the RRforCXof0.5to2.0ppmisl.73(1.42to2.11),andtheRRforCX _ 2.0 is I .70 (1.32 to 2.18). Hourly workers have a significantly higher RR than salaried workers (RR = 1.58). Similar increased RRs are observed for all cancers and all causes. The RRs for different length of exposure are not significantly elevated because of the mathematical relationship betweencumulativeexposure,lengtbofexposure,andlevel of exposure and because of the possibility that workers exposed to very high levels of exposure may tend to leave employment early.
B.V. (Biomedical
Division)