This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yengi, L. Articles by Fryer, A. A. Search for Related Content PubMed PubMed Citation Articles by Yengi, L. Articles by Fryer, A. A.

Polymorphism at the Glutathione S-Transferase Locus GSTM3: Interactions with Cytochrome P450 and Glutathione S-Transferase Genotypes as Risk Factors for Multiple Cutaneous Basal Cell Carcinoma¹

Clinical Biochemistry Research Group, School of Postgraduate Medicine, Keele University, Central Pathology Laboratory [L. Y., A. I., J. G., J. A., L. B., P. H., R. C. S., A. A. F.], and Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire ST4 7QB [A. S., J. T. L., A. H. H.], Department of Dermatology, Royal Cornwall Hospitals, Truro, Cornwall TR1 2HZ [B. B.], England; Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland DD1 9SY [J. D. H.]; and Department of Mathematics, University of Keele, Keele, Staffordshire, England ST5 5BG [P. W. J.]

The influence of polymorphism in the glutathione S-transferase, GSTM3 gene on susceptibility to cutaneous basal cell carcinoma (BCC) has been investigated. We have reported previously two GSTM3 alleles, GSTM3*A and GSTM3*B, distinguished by a recognition motif for the YY1 transcription factor in GSTM3*B. In this study, immunohistochemistry was used to identify GSTM3 expression in the epidermis of skin samples from 11 controls and 9 patients with BCC. A PCR method was used to identify GSTM3*A and GSTM3*B and thereby the GSTM3 AA, GSTM3 AB, and GSTM3 BB genotypes in 300 controls and 286 Caucasians with 1–35 primary BCCs. Genotypes at GSTM1, GSTT1, and the cytochrome P450 CYP1A1 and CYP2D6 loci were also determined. Frequencies of GSTM3, GSTM1, GSTT1, CYP2D6, and CYP1A1 genotypes in the cases and controls were not different. Dividing the BCC cases into groups of 92 patients with 1 lesion and 194 patients with 2–35 lesions showed that the frequencies of GSTM3 BB (2.6%) and GSTM1 A/B (1.3%) in the group with 2–35 tumors were almost significantly lower than in the group with 1 lesion (7.6%, exact P = 0.0601, x²₁ = 3.390; 6.5%, exact P = 0.055, x²₁ = 4.946, respectively). Within the cases with 2–35 tumors, a Poisson regression model was used to identify genotypes, characteristics such as skin type, and interactions between genotypes and characteristics associated with increasing numbers of tumors. This showed, after correction for male gender and age, that GSTM3 AA was not associated with risk of increased numbers of tumors, although in combination with skin type 1, GSTM1 null, and CYP1A1 m1m1, the genotype did confer increased risk (P < 0.001, rate ratio, 2.058; P < 0.001, rate ratio, 1.606; P < 0.001, rate ratio, 1.470, respectively). The data suggest that, like other allelic GST, GSTM3 influences cancer risk. As GSTM3 AA was associated with increased tumor numbers, it appears that YY1 acts as an activator of the recognition motif in GSTM3*B.

¹ We gratefully acknowledge the support of the Cancer Research Campaign (Project Grant SP2207/0201).

² To whom requests for reprints should be addressed. Phone: (01782) 716676; Fax: (01782) 716646.

Received 2/12/96. Accepted 3/12/96.

This article has been cited by other articles:

				M. Jain, S. Kumar, P. Lal, A. Tiwari, U. C. Ghoshal, and B. Mittal Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 178 - 181. [Abstract] [Full Text] [PDF]

				A. J. De Roos, N. Rothman, M. Brown, D. A. Bell, G. S. Pittman, W. R. Shapiro, R. G. Selker, H. A. Fine, P. M. Black, and P. D. Inskip Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors. Neuro-oncol, April 1, 2006; 8(2): 145 - 155. [Abstract] [Full Text] [PDF]

				X (R) Yang, R M Pfeiffer, and A M Goldstein Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450 (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in families with the naevoid basal cell carcinoma syndrome. J. Med. Genet., April 1, 2006; 43(4): e16 - e16. [Abstract] [Full Text] [PDF]

				L. F. Masson, L. Sharp, S. C. Cotton, and J. Little Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915. [Abstract] [Full Text] [PDF]

				X. Liu, M. R. Campbell, G. S. Pittman, E. C. Faulkner, M. A. Watson, and D. A. Bell Expression-Based Discovery of Variation in the Human Glutathione S-Transferase M3 Promoter and Functional Analysis in a Glioma Cell Line Using Allele-Specific Chromatin Immunoprecipitation Cancer Res., January 1, 2005; 65(1): 99 - 104. [Abstract] [Full Text] [PDF]

				A. A. Fryer, H. M. Ramsay, T. J. Lovatt, P. W. Jones, C. M. Hawley, D. L. Nicol, R. C. Strange, and P. N. Harden Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients Carcinogenesis, January 1, 2005; 26(1): 185 - 191. [Abstract] [Full Text] [PDF]

				P. Barnette, R. Scholl, M. Blandford, L. Ballard, A. Tsodikov, J. Magee, S. Williams, M. Robertson, F. Ali-Osman, R. Lemons, et al. High-Throughput Detection of Glutathione S-Transferase Polymorphic Alleles in a Pediatric Cancer Population Cancer Epidemiol. Biomarkers Prev., February 1, 2004; 13(2): 304 - 313. [Abstract] [Full Text] [PDF]

				A. Loktionov, M. A. Watson, M. Gunter, W. S.L. Stebbings, C. T.M. Speakman, and S. A. Bingham Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor Carcinogenesis, July 1, 2001; 22(7): 1053 - 1060. [Abstract] [Full Text] [PDF]

				K. Mitrunen, N. Jourenkova, V. Kataja, M. Eskelinen, V.-M. Kosma, S. Benhamou, H. Vainio, M. Uusitupa, and A. Hirvonen Glutathione S-Transferase M1, M3, P1, and T1 Genetic Polymorphisms and Susceptibility to Breast Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 229 - 236. [Abstract] [Full Text]

				V. Cortessis, K. Siegmund, Q. Chen, N. Zhou, A. Diep, H. Frankl, E. Lee, Q.-s. Zhu, R. Haile, and D. Levy A Case-Control Study of Microsomal Epoxide Hydrolase, Smoking, Meat Consumption, Glutathione S-Transferase M3, and Risk of Colorectal Adenomas Cancer Res., March 1, 2001; 61(6): 2381 - 2385. [Abstract] [Full Text]

				A. A. FRYER, A. BIANCO, M. HEPPLE, P. W. JONES, R. C. STRANGE, and M. A. SPITERI Polymorphism at the Glutathione S-transferase GSTP1 Locus . A New Marker for Bronchial Hyperresponsiveness and Asthma Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1437 - 1442. [Abstract] [Full Text]

				C. L. A. Mann, M. B. Davies, M. D. Boggild, J. Alldersea, A. A. Fryer, P. W. Jones, C. Ko Ko, C. Young, R. C. Strange, and C. P. Hawkins Glutathione S-transferase polymorphisms in MS: Their relationship to disability Neurology, February 8, 2000; 54(3): 552 - 552. [Abstract] [Full Text] [PDF]

				S. Rollinson, P. Roddam, E. Kane, E. Roman, R. Cartwright, A. Jack, and G. J. Morgan Polymorphic variation within the glutathione S-transferase genes and risk of adult acute leukaemia Carcinogenesis, January 1, 2000; 21(1): 43 - 47. [Abstract] [Full Text] [PDF]

				A. Clairmont, H. Sies, S. Ramachandran, J. T. Lear, A. G. Smith, B. Bowers, P. W. Jones, A. A. Fryer, and R. C. Strange Association of NAD(P)H:quinone oxidoreductase (NQO1) null with numbers of basal cell carcinomas: use of a multivariate model to rank the relative importance of this polymorphism and those at other relevant loci Carcinogenesis, July 1, 1999; 20(7): 1235 - 1240. [Abstract] [Full Text] [PDF]

				M. D’Errico, A. Calcagnile, I. Iavarone, F. Sera, G. Baliva, L. M. Chinni, R. Corona, P. Pasquini, and E. Dogliotti Factors That Influence the DNA Repair Capacity of Normal and Skin Cancer-affected Individuals Cancer Epidemiol. Biomarkers Prev., June 1, 1999; 8(6): 553 - 559. [Abstract] [Full Text]

				D. L Mattey, A. B Hassell, M. Plant, P. T Dawes, W. R Ollier, P. W Jones, A. A Fryer, J. E Alldersea, and R. C Strange Association of polymorphism in glutathione S-transferase loci with susceptibility and outcome in rheumatoid arthritis: comparison with the shared epitope Ann Rheum Dis, March 1, 1999; 58(3): 164 - 168. [Abstract] [Full Text]

				N. Jourenkova-Mironova, A. Voho, C. Bouchardy, H. Wikman, P. Dayer, S. Benhamou, and A. Hirvonen Glutathione S-Transferase GSTM3 and GSTP1 Genotypes and Larynx Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 1999; 8(2): 185 - 188. [Abstract] [Full Text]

				D. Harrison, A. Cantlay, F. Rae, D. Lamb, and C. Smith Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer Human and Experimental Toxicology, July 1, 1997; 16(7): 356 - 360. [Abstract] [PDF]