title: The GSTM1 null genotype confers an increased risk for solar keratosis development in an Australian Caucasian population.
abstract: Solar keratoses affect approximately 50% of Australian Caucasians aged over 40 y. Solar keratoses can undergo malignant transformation into squamous cell carcinoma followed by possible metastasis and are risk factors for basal cell carcinoma, melanoma, and squamous cell carcinoma. The glutathione-S-transferase genes play a part in detoxification of carcinogens and mutagens, including some produced by ultraviolet radiation. This study examined the role of glutathione-S-transferase M1, T1, P1, and Z1 gene polymorphisms in susceptibility to solar keratoses development. Using DNA samples from volunteers involved in the Nambour Skin Cancer Prevention Trial, allele and genotype frequencies were determined using polymerase chain reaction and restriction enzyme digestion. No significant differences were detected in glutathione-S-transferase P1 and glutathione-S-transferase Z1 allele or genotype frequencies; however, a significant association between glutathione-S-transferase M1 genotypes and solar keratoses development was detected (p=0.003) with null individuals having an approximate 2-fold increase in risk for solar keratoses development (odds ratio: 2.1; confidence interval: 1.3-3.5) and a significantly higher increase in risk in conjunction with high outdoor exposure (odds ratio: 3.4; confidence interval: 1.9-6.3). Also, a difference in glutathione-S-transferase T1 genotype frequencies was detected (p=0.039), although considering that multiple testing was undertaken, this was found not to be significant. Fair skin and inability to tan were found to be highly significant risk factors for solar keratoses development with odds ratios of 18.5 (confidence interval: 5.7-59.9) and 7.4 (confidence interval: 2.6-21.0), respectively. Overall, glutathione-S-transferase M1 conferred a significant increase in risk of solar keratoses development, particularly in the presence of high outdoor exposure and synergistically with known phenotypic risk factors of fair skin and inability to tan.
authors.affiliation: Genomics Research Center, School of Health Science, Griffith University, Gold Coast, QLD, Australia.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Bridget
authors.initials: B
authors.lastname: Appleyard
authors.forename: Phil
authors.initials: P
authors.lastname: Gaffney
authors.forename: Adele
authors.initials: A
authors.lastname: Green
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D001315:Australia; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007642:Keratosis / Q000453:epidemiology* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D012880:Skin Pigmentation; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D044465:White People / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase