U106380.pdf (10.66 MB)
Susceptibility to basal cell carcinoma (BCC) : the influence of individual characteristics and polymorphism in loci encoding detoxifying enzymes
thesisposted on 2014-12-15, 10:31 authored by John T. Lear
BCC is the commonest malignancy in white people and presents a great burden to health care provision. The genetic factors and individual characteristics associated with susceptibility to this cancer are still largely unclear. Since ultraviolet radiation constitutes an oxidative stress to skin cells, the ability to deal with the products of oxidative stress-induced damage may be important in determining BCC risk. The influence of detoxifying enzyme gene polymorphisms (glutathione S-transferases (GST) GSTM1, GSTT1, GSTM3) and cytochrome P450's (CYP) CYP1A1 and CYP2D6 on susceptibility to BCC was assessed. The influence of individual characteristics was also studied. Skin type 1, blue/green eyes, red/blonde hair and social class 1 or 2 were all significant risk factors for BCC. Truncal site of BCC was associated with multiple lesions. Patients with melanoma were younger, more likely to be female, have red/blonde hair and a truncal tumour when compared to those with a BCC. Patient's with skin cancers of different histological types were more likely to have truncal BCC and be of skin type 1. The GSTM1 A/B genotype was protective against multiple tumours. GSTM1 null in combination with some of these factors influenced BCC number and time to next tumour presentation. GSTT1 null influenced BCC accrual and tumour site. Interactions between GSTM3 AA, skin type 1 and other genotypes were associated with multiple BCC, CYP1A m1m1 was associated with increased numbers of lesions. The CYP1A1 lle/lle genotype was more common in those with a truncal tumour. The CYP2D6 EM genotype influenced total number of BCC, rate of accrual and time to next tumour presentation. These results indicate that individual variation in the ability to deal with products of ultraviolet and/or chemical-induced oxidative stress is important in BCC pathogenesis and indicates a potential use of individual characteristics and genetic markers in BCC follow-up strategies.
Date of award1998-01-01
Awarding institutionUniversity of Leicester