Several epidemiologic studies suggest that GST-M1 null genotype may be a susceptibility marker for lung cancer among persons who smoke cigarettes. Since current smoking is also strongly related to the risk of squamous anogenital cancer, we propose to examine whether GST-M1 genotype is associated with the incidence of cancers of the anus, penis, cervix, vagina and vulva. Peripheral blood specimens will be obtained from persons with one of these cancers who, as part of our ongoing, population-based case-control study of anogenital tumors in Western Washington, will be identified and interviewed from January 1993 to December l994. Samples will also be obtained from population-based controls who are being selected during the same period using random digit dialing; they will be frequency matched to the age distribution of the cases by 5-year intervals. The GST-M1 genotypes of cases and controls will be determined by polymerase chain reaction (PCR) of DNA isolated from peripheral blood lymphocytes of cases and controls using primers that are specific for intron 5 sequence of human GST-M1 DNA. Results of PCR analyses will be confirmed by Southern blot analyses using a GST-M1 cDNA probe. If the GST- M1 null phenotype is found in a greater proportion of cases of squamous anogenital cancer than in controls---particularly among persons who smoke cigarettes---we will gain some insight into the means by which smoking predisposes to the occurrence of these malignancies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES006728-02
Application #
2155590
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1994-05-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Chen, C; Madeleine, M M; Weiss, N S et al. (1999) Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: a population-based case-control study. Am J Epidemiol 150:568-72
Chen, C; Madeleine, M M; Weiss, N S et al. (1999) Glutathione S-transferase M1 genotypes and the risk of vulvar cancer: a population-based case-control study. Am J Epidemiol 150:437-42
Chen, C; Nirunsuksiri, W (1999) Decreased expression of glutathione S-transferase M1 in HPV16-transfected human cervical keratinocytes in culture. Carcinogenesis 20:699-703
Chen, C; Cook, L S; Li, X Y et al. (1999) CYP2D6 genotype and the incidence of anal and vulvar cancer. Cancer Epidemiol Biomarkers Prev 8:317-21
Chen, C; Madeleine, M M; Lubinski, C et al. (1996) Glutathione S-transferase M1 genotypes and the risk of anal cancer: a population-based case-control study. Cancer Epidemiol Biomarkers Prev 5:985-91