Genetic polymorphisms in DNA repair and oxidative stress pathways associated with malignant melanoma susceptibility

Abstract Background Base excision repair (BER) and nucleotide excision repair (NER) pathways eliminate a wide variety of DNA damage, including UV photoproducts. The ability of each individual to repair DNA damage following different causes might explain at least in part the variability in cancer susceptibility. Moreover, inflammatory response to UV exposure may further contribute to skin carcinogenesis by oxidative stress mechanisms. Single nucleotide polymorphisms in genes encoding various DNA-repair enzymes and oxidative stress factors may be candidate low-penetrance variants with a role in susceptibility to different cancers, particularly in those with aetiologies linked to environmental exposure, such as malignant melanoma (MM). Methods In this case–control study, 684 Spanish sporadic MM patients and 406 cancer-free control subjects were included and the role of 46 polymorphisms belonging to 16 BER and NER genes as well as 11 genes involved in oxidative stress processes were investigated. Results One polymorphism was identified to be individually associated with MM in the Spanish population. The variant was found in the NOS1 oxidative stress gene (rs2682826; p - value =0.01). These results suggest a putative role of oxidative stress processes in the genetic predisposition to melanoma. Conclusion To the authors' knowledge, this is the largest DNA repair-related SNP study in melanoma risk conducted in the Spanish population up to now. Furthermore, it also represents a comprehensive genetic study of several oxidative stress polymorphisms tested in relation to MM susceptibility.