Glucose 6-phosphate dehydrogenase deficiency and skin cancer: A retrospective study assessing cutaneous malignancy risk.

e21576 Background: Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme within the pentose phosphate pathway (PPP) that produces nicotinamide adenine dinucleotide phosphate (NADPH), which can protect from oxidative damage. In cancer, the PPP has been shown to be a source of oxidative stress resistance for tumors. Though, inhibition of G6PD may still have compensatory pathways for cancer survival. Several studies have indicated that G6PD may be an essential redox element for melanoma. Experimental studies including in vitro models have linked G6PD to skin cancer. Additionally, there has been evidence of a protective effect from G6PD deficiency in gastric, hepatocellular, and colorectal cancer; while, breast, prostate, lung, and hematological cancer have had evidence of no difference in risk. To date, there has been no study of skin cancer risk in G6PD-deficient patients. Methods: The TriNetX US database was utilized to provide real-world, de-identified data of 117 million patients. Exposed patients were defined by the International Classification of Disease (ICD-10) coding, D55.0 for G6PD deficiency. The control cohort was defined by having at least 1 annual physical examination (Z00.0) with no history of G6PD deficiency. The cohorts were propensity score matched 1:1 by current age, sex, Hispanic ethnicity, and Black and White race. Results: 15,848 patients met inclusion criteria of G6PD deficiency. After cohort matching, 15,346 patients were included. G6PD-deficient patients did not have significantly different risk of melanoma (relative risk (RR) 1.368, p=0.2964), squamous cell carcinoma (SCC) (RR=1.4, p=0.1019), and overall non-melanoma skin cancer (NMSC) (RR= 0.9018, p=0.4497) compared to unexposed patients. G6PD-deficient patients did have significantly decreased risk of basal cell carcinoma (BCC) (RR=0.625, p=0.0124). Conclusions: We share the first epidemiological results of skin cancer risk in these patients. Our study suggests that individuals with deficiency may not have a difference in overall incidence of skin cancer and melanoma. This finding aligns with prior experimental evidence of lack of impact on primary cutaneous tumors, as well as discussion of potential compensatory pathways. The role of G6PD deficiency in cancer susceptibility has been inconsistent across malignancies, and our results with BCC underscore the heterogeneity of redox biology across tissue types and may align with proposed tumor sensitivity to oxidative stress.