Evidence that oxidative stress is a risk factor for the development of squamous cell carcinoma in renal transplant...

Renal transplant patients are at a greatly increased risk of skin malignancy, particularly squamous cell carcinoma (SCC), a tumor closely associated with UV exposure. There is also significant interindividual skin cancer risk among transplant patients, with evidence suggesting that this derives from variation in response to oxidative stress. Our aim was to assess urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), by liquid chromatography-tandem mass spectrometry, in renal transplant patients with and without SCC. The relationships between SCC and urinary 8-oxodG were analyzed by conditional logistic regression and those between 8-oxodG and other candidate variables by linear regression, correcting for the effect of SCC. In SCC patients, urinary 8-oxodG was significantly elevated (p=0.03), both pre- and post-tumor development, compared to non-SCC transplant patients. Secondary analyses indicated that 8-oxodG was related to current heavy smoking (p=0.02) and darker skin type (p=0.02), but not measures of previous chronic sun exposure or current age and gender. Although subject numbers were limited, immunosuppression with azathioprine was positively associated with 8-oxodG in all patients combined (p=0.02). These results demonstrate, for the first time, that a subpopulation of renal transplant patients is under greater oxidative burden, and it is this population that is particularly predisposed to skin cancer.