Polymorphisms in DNA repair related genes as risk factors for lung cancer in Cuban population: a case control study

Single nucleotide variants are important factors involved in lung cancer onset and prognosis. In Cuba, there are scarce studies evaluating the possible association between genetic variants and lung cancer. Here, we described the frequency distribution of genetic variants in DNA repair related genes and assessed their impact on lung cancer susceptibility and survival prognosis in a cohort of Cuban population METHODS: Case-Control study included 300 lung cancer patients and 300 control subjects. Variants: rs1042522, rs11016879, rs13181, rs25487 and rs861539 were genotyped. The association analysis was evaluated by logistic regression and the impact on overall survival was estimated by Kaplan-Meier and Cox regression analyses.

Genotype frequencies were in Hardy-Weinberg equilibrium except for rs1042522 in patients. The heterozygote of this variant was associated with low risk to lung cancer (Overdominant, OR: 0.53, p = 0.01). Conversely, rs25487 showed trend to additive genotype risk (Additive model, OR:1.61, p = 0.01). Differences in genotype frequencies according to skin color of controls were detected for rs1042522 and rs861539 (p = 0.01). The rs11016879 and rs1042522 showed joint protective effects with skin color. Interaction between rs25487 and cigarette smoking analysis revealed higher lung cancer risk (OR = 3.72, p = 0.03, p-interaction: 0.01). Interaction between alcohol consumption and rs13181 reached borderline significance for decreased risk of lung cancer (OR = 0.25, p = 0.03, p-interaction: 0.06). In addition, rs11016879 alternative allele was an independent factor for higher mean 5-years overall survival (log-rank test p = 0.03).

The study provides the first data evaluating the relevance of genetic variants in DNA damage repair related genes for lung cancer management in Cuban population. Our findings indicate a significant contribution of the genetic variants to lung cancer susceptibility and highlights the importance of considering skin color within analyses for disease susceptibility in Cuban population.