Ultraviolet radiation (UVR) is present in the sunlight that reaches the Earth, and can
also be artificially produced. Artificial sources of UVR can be used therapeutically,
for the treatment of skin disease such as psoriasis. UVR is a source of DNA damage,
and the major causative agent for the development of skin cancers. UV-induced DNA
damage can be repaired by a number of DNA repair pathways, principally the
nucleotide excision repair (NER) pathway and the base excision repair pathway
(BER), preventing DNA lesions from becoming incorporated into the genome.
Defects in the genes involved with NER lead to three, rare, recessive syndromes,
Xeroderma pigmentosum (XP), Cockayne's Syndrome (CS) and Trichothiodystrophy
(TTD). Individuals affected with any of these syndromes have varying degrees of
photosensitivity, with XP patients also having a greater than 1000 fold increased risk
of skin cancer. As UVR is one of the most frequently exposed to sources of DNA
damage, and also used as a therapeutic reagent, it would be useful to have a genetic
marker which might predict an individual's response to UVR.
Polymorphisms in the genes involved with the NER, BER and other repair pathways
will be examined in this thesis, to determine if any are associated with sensitivity to
UVR. Sensitivity to UVR will be determined as the level of erythema induced by an
incremental range ofUV doses in two independent study groups, of 74 and 31
individuals. Erythema will be measured using reflectance spectrophotometry, which is
an analytical measure, rather than the widely used minimal erythemal dose (MED).