A novel polymorphism in the TERT gene is associated with lower survival in male patients with melanoma.

BACKGROUND

In recent years, several genes beyond BRAF have been identified as recurrently mutated in melanoma, including hTERT (human telomerase reverse transcriptase). While the most extensively studied TERT mutations occur within its promoter region, intron 4 has also been implicated as a locus associated with cancer susceptibility. This study aimed to investigate the role of the rs7734992 polymorphism, located in a potentially functional site within intron 4 of the TERT gene, in melanoma risk and prognosis, as well as to evaluate possible sex-specific effects.

METHODS

A total of 1,083 melanoma patients with follow-up data exceeding six months were retrospectively included. Genotyping was performed on DNA extracted from peripheral blood using a TaqMan assay.

RESULTS

Male patients carrying the TT genotype of rs7734992 exhibited significantly poorer survival (OR = 3,145, 95% Cis = 1,465—6,753; p = 0.003) compared with females, although no association was found between this polymorphism and melanoma risk.

CONCLUSIONS

These findings suggest that the rs7734992 polymorphism may influence melanoma prognosis in male patients. While this study provides novel insights into melanoma genetics, functional investigations are warranted to clarify the biological mechanisms through which rs7734992 could affect male survival, and to explore whether the TT genotype, in conjunction with sex hormone levels, modulates telomerase activity and, consequently, telomere length.