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Assessment of cancer susceptibility in humans by use of genetic polymorphisms in carcinogen metabolism
Abstracts/Lung
Cancer
Man-made vitreous fibers and risk of respiratory system cancer: A review of the epidemiologic evidence Lee I-M, Hennekens CH, Trichopoulos D, Buring JE. HarvardMedical School, Brigham and Women b Hospital, 900 Commonwealth Avenue East9 Boston, A&t 02215. J Occup Environ Med 1995;37:725-38.
Because asbestos has been demonstrated to cause lung cancer, the issue regarding safety ofother fibers, including man-madevitreous fibers (MMVF), has been raised. We reviewed the available evidence, in particular the epidemiologic data, on MMVF and the risk of respiratory system cancer. Glass fibers (especially glass wool) have been studied most extensively. Taken together, the data indicate that among those occupationally exposed, glass fibers do not appear to increase ask of respiratory system cancer. Ofsix studies that specifically examined rock and slag wool workers, three reported excesses in respiratory system cancer among such workers. Two of these three studies, however, did not control cigarette smoking, a powerful predictor of such cancers. There are rio published studies, in human, of refractory ceramic fibers. Future studies evaluating the potential of MMVF to increase risk of respiratory system cancer will not add to existing knowledge if investigators do not address potential confounding by cigarette smoking and other workplace carcinogens. Analysis of the characteristics of human papilloma virus infection in 85 neoplasms of the respiratory system in adult patients Xing L, Liu H, Si J. Luoyang Medical College Hospital. Luoyang 471003. Chin J Oncol 1994;16:424-7. Eighty-five neoplastic tissues of respiratory system in Chinese adult patients were searched for HPV by multiple PCR and in situ hybridization. In 13 of the specimens examined, HPV DNA was identified (15.3%), including 6 of 36 cases of pharyngolaryngeal neoplasms (16.6%) and 7 of 49 cases of lung squamous cell carcinomas (14.2%). Among the 13 cases tumor specimen, most of them were positive for HPV6/11 types and a few were double positive for HPV 61 I1 and 16 types. Many tumor cells positive for HPV DNA on in situ hybridization were morphologically similar lo those koilocytes in genital condylomas. HPV infection in 85 neoplasms was characterized by the fact that the same genotypes of HPV were detected in upper and lower respiratory tract and that the dominant virus types detected were HPV 6/l 1 types. The detection rate of HPV was a little higher in the upper than that in the lower respiratory tract and the HPV DNA positive tumors had similar histological appearance. The results suggest that HPV infection in the neoplasms of the upper and the lower airways is related to each other with similar mode of transmission.
Distribution of GSTMl null genotype in relation to gender, age and smoking status in Japanese lung cancer patients Kihara M, Noda K, Kihara M. Department of Epidemiology Kanagawa Cancer
Ct,: Reseamh
Inst..
54-2 Nakao-cho,
Asahi-ku,
Yokohama
241.
Pharmacogenetics 1995;5:Spec Iss:S74-9. GSTMI gene deficiency has been shown to occur in approximately halfof the populations ofvarious ethnic origins and has been implicated as a factor for elevated risk for lung cancers. However the results have been variable or even contlicting between the studies. In an attempt to explore the reason for such a diversity, we studied the distribution of GSTM 1 genotypes in relation to gender, age and smoking status in 447 Japanese lung cancer patients and 469 community controls. We found: (I) that in squamous and small cell carcinomas GSTMl null genotype distributed markedly more in females than males especially among the patients aged < 70 years (male 57.4%. female 100.0%); (2) that GSTMI null genotype distributed generally more in patients aged < 70 years
13 (199s)
185-232
187
(58.3%) than those aged 70 years (50.0%) irrespective of histologies except for small cell carcinoma; and (3) that proportion ofGSTMl null genotype increased dependent on the extent of tobacco smoke exposure in male patients having squamous and small cell carcinomas aged < 70 years, and remained high but independent of the smoking index in adenoavcinoma and unchanged in never- or exsmokers from the control level (48.6%). The present study thus suggests that composition of GSTMl genotypes in patients is significantly affected by gender, age and smoking status, which should be taken into consideration in any attempt to determine the association of GSTMl genotypes for risk assessment. With the diverse of GSTMl null genotype variability behucen patients of different histologies, our results were also suggestive of ditferent carcinogenic involvement of GSTMl deficiency among different histological cell types. Assessment of cancer susceptibility in humans by use of genetic polymorphisms in carcinogen metabolism Ikawa S, Uematsu F, Watanabe K, Kimpara T, Osada M, Hossain A. Seityo-machi, Aoba-ku. Sendai 98&?7. Pharmacogenetics 1995;5:Spec Iss:Sl54-60. Prevention is an important and effective measure for reducing death caused by cancer. Thus information on individual susceptibility to cancer is valuable in suggesting high risk individuals to avoid intake of carcinogenic substances and receive frequent physical screening. To this end, polymorphisms found within cytochrome P450 (CYF’) genes implicated in the metabolism of procarcinogens are expected to be good genetic targets in assessing human cancer susceptibility. We have found polymorphisms in the CYPZEI and CYPIAI genes associated with lung cancer susceptibility, though there were some discrepancies from observations made by other investigators. Discrepancies among investigators from different regions, however, are very common in these pharmacogenetic studies. We present an explanation for these discrepancies, difficulties associated with prediction of relative risk of individuals. and future directions. Air pollution and lung cancer in Trieste, Italy Barbone F, Bovenzi M, Cavallieri F, Stanta G. CJnit of Hygiene Epidemiology. DPMSC, Udine. Am JEpidemiol
University
of Udine,
Ma Colugna,
and 42, 33100
1995;141:1161-9. To investigate the relation between air pollution and histologic type of lung cancer, the authors conducted a case-control study among men who had died in Trieste, Italy, from 1979 to I981 and from 1985 to 1986. Through the local autopsy registry. 755 cases of lung cancer and 755 controls were identified. Information on smoking habits, occupation, and place of residence was obtained from each subject’s next of kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Logistic regression was used to evaluate the effect of residence and air pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure lo occupational carcinogens, and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined @ = 0.022). for small cell carcinoma @ = 0.016), and for large cell carcinoma (p = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI) 0.4-1.0). The RR was 1.5 (95% CI 1.O-2.2) for residents of the center of the city and 1.4 (95% CI 1 .O-2. I) for residents of the industrial area. In the center of the city, the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area, the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer.
Cancer
Man-made vitreous fibers and risk of respiratory system cancer: A review of the epidemiologic evidence Lee I-M, Hennekens CH, Trichopoulos D, Buring JE. HarvardMedical School, Brigham and Women b Hospital, 900 Commonwealth Avenue East9 Boston, A&t 02215. J Occup Environ Med 1995;37:725-38.
Because asbestos has been demonstrated to cause lung cancer, the issue regarding safety ofother fibers, including man-madevitreous fibers (MMVF), has been raised. We reviewed the available evidence, in particular the epidemiologic data, on MMVF and the risk of respiratory system cancer. Glass fibers (especially glass wool) have been studied most extensively. Taken together, the data indicate that among those occupationally exposed, glass fibers do not appear to increase ask of respiratory system cancer. Ofsix studies that specifically examined rock and slag wool workers, three reported excesses in respiratory system cancer among such workers. Two of these three studies, however, did not control cigarette smoking, a powerful predictor of such cancers. There are rio published studies, in human, of refractory ceramic fibers. Future studies evaluating the potential of MMVF to increase risk of respiratory system cancer will not add to existing knowledge if investigators do not address potential confounding by cigarette smoking and other workplace carcinogens. Analysis of the characteristics of human papilloma virus infection in 85 neoplasms of the respiratory system in adult patients Xing L, Liu H, Si J. Luoyang Medical College Hospital. Luoyang 471003. Chin J Oncol 1994;16:424-7. Eighty-five neoplastic tissues of respiratory system in Chinese adult patients were searched for HPV by multiple PCR and in situ hybridization. In 13 of the specimens examined, HPV DNA was identified (15.3%), including 6 of 36 cases of pharyngolaryngeal neoplasms (16.6%) and 7 of 49 cases of lung squamous cell carcinomas (14.2%). Among the 13 cases tumor specimen, most of them were positive for HPV6/11 types and a few were double positive for HPV 61 I1 and 16 types. Many tumor cells positive for HPV DNA on in situ hybridization were morphologically similar lo those koilocytes in genital condylomas. HPV infection in 85 neoplasms was characterized by the fact that the same genotypes of HPV were detected in upper and lower respiratory tract and that the dominant virus types detected were HPV 6/l 1 types. The detection rate of HPV was a little higher in the upper than that in the lower respiratory tract and the HPV DNA positive tumors had similar histological appearance. The results suggest that HPV infection in the neoplasms of the upper and the lower airways is related to each other with similar mode of transmission.
Distribution of GSTMl null genotype in relation to gender, age and smoking status in Japanese lung cancer patients Kihara M, Noda K, Kihara M. Department of Epidemiology Kanagawa Cancer
Ct,: Reseamh
Inst..
54-2 Nakao-cho,
Asahi-ku,
Yokohama
241.
Pharmacogenetics 1995;5:Spec Iss:S74-9. GSTMI gene deficiency has been shown to occur in approximately halfof the populations ofvarious ethnic origins and has been implicated as a factor for elevated risk for lung cancers. However the results have been variable or even contlicting between the studies. In an attempt to explore the reason for such a diversity, we studied the distribution of GSTM 1 genotypes in relation to gender, age and smoking status in 447 Japanese lung cancer patients and 469 community controls. We found: (I) that in squamous and small cell carcinomas GSTMl null genotype distributed markedly more in females than males especially among the patients aged < 70 years (male 57.4%. female 100.0%); (2) that GSTMI null genotype distributed generally more in patients aged < 70 years
13 (199s)
185-232
187
(58.3%) than those aged 70 years (50.0%) irrespective of histologies except for small cell carcinoma; and (3) that proportion ofGSTMl null genotype increased dependent on the extent of tobacco smoke exposure in male patients having squamous and small cell carcinomas aged < 70 years, and remained high but independent of the smoking index in adenoavcinoma and unchanged in never- or exsmokers from the control level (48.6%). The present study thus suggests that composition of GSTMl genotypes in patients is significantly affected by gender, age and smoking status, which should be taken into consideration in any attempt to determine the association of GSTMl genotypes for risk assessment. With the diverse of GSTMl null genotype variability behucen patients of different histologies, our results were also suggestive of ditferent carcinogenic involvement of GSTMl deficiency among different histological cell types. Assessment of cancer susceptibility in humans by use of genetic polymorphisms in carcinogen metabolism Ikawa S, Uematsu F, Watanabe K, Kimpara T, Osada M, Hossain A. Seityo-machi, Aoba-ku. Sendai 98&?7. Pharmacogenetics 1995;5:Spec Iss:Sl54-60. Prevention is an important and effective measure for reducing death caused by cancer. Thus information on individual susceptibility to cancer is valuable in suggesting high risk individuals to avoid intake of carcinogenic substances and receive frequent physical screening. To this end, polymorphisms found within cytochrome P450 (CYF’) genes implicated in the metabolism of procarcinogens are expected to be good genetic targets in assessing human cancer susceptibility. We have found polymorphisms in the CYPZEI and CYPIAI genes associated with lung cancer susceptibility, though there were some discrepancies from observations made by other investigators. Discrepancies among investigators from different regions, however, are very common in these pharmacogenetic studies. We present an explanation for these discrepancies, difficulties associated with prediction of relative risk of individuals. and future directions. Air pollution and lung cancer in Trieste, Italy Barbone F, Bovenzi M, Cavallieri F, Stanta G. CJnit of Hygiene Epidemiology. DPMSC, Udine. Am JEpidemiol
University
of Udine,
Ma Colugna,
and 42, 33100
1995;141:1161-9. To investigate the relation between air pollution and histologic type of lung cancer, the authors conducted a case-control study among men who had died in Trieste, Italy, from 1979 to I981 and from 1985 to 1986. Through the local autopsy registry. 755 cases of lung cancer and 755 controls were identified. Information on smoking habits, occupation, and place of residence was obtained from each subject’s next of kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Logistic regression was used to evaluate the effect of residence and air pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure lo occupational carcinogens, and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined @ = 0.022). for small cell carcinoma @ = 0.016), and for large cell carcinoma (p = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI) 0.4-1.0). The RR was 1.5 (95% CI 1.O-2.2) for residents of the center of the city and 1.4 (95% CI 1 .O-2. I) for residents of the industrial area. In the center of the city, the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area, the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer.