In an important advancement for lung cancer research within diverse populations, a new study conducted in Cuba sheds light on the genetic underpinnings that influence lung cancer susceptibility and patient survival. This research provides a critical analysis of polymorphisms – specific variations in DNA sequence – in genes responsible for DNA repair mechanisms, illuminating their role as risk factors for lung cancer among Cubans. With lung cancer remaining the leading cause of cancer-related deaths worldwide, understanding genetic influences could pave the way for more precise risk assessments and tailored therapeutic approaches in genetically admixed populations like Cuba.
Genetic polymorphisms in DNA repair genes have long been suspected of modulating individual vulnerability to cancers, including lung cancer, but data concerning Latin American populations are scarce. The Cuban population, characterized by its unique genetic admixture resulting from diverse African, European, and Indigenous ancestries, presents a compelling context for investigating genetic variations associated with lung cancer risk. The study meticulously analyzed five key single nucleotide polymorphisms (SNPs) – rs1042522, rs11016879, rs13181, rs25487, and rs861539 – focusing on their frequency distribution among 300 lung cancer patients and 300 matched control subjects.
One of the standout findings involves the SNP rs1042522, located in the TP53 gene, a tumor suppressor critically involved in DNA repair and apoptosis regulation. The heterozygous genotype of this variant was associated with a notably reduced risk of developing lung cancer. This protective effect, observed under an overdominant genetic model with an odds ratio (OR) of 0.53, suggests a complex genetic interplay possibly modulating cellular DNA damage response efficacy and influencing carcinogenesis susceptibility.
Conversely, the variant rs25487 in the XRCC1 gene showed a contrasting trend. This SNP displayed an additive genetic risk pattern, signifying that each additional risk allele incrementally raised lung cancer susceptibility (OR 1.61). XRCC1 is central to the base excision repair pathway, repairing single-strand breaks in DNA; thus, alterations in this gene potentially compromise genomic stability, fostering oncogenic mutations especially in lung tissue chronically exposed to carcinogens such as tobacco smoke.
Remarkably, the genetic data revealed differential distribution patterns linked to phenotypic traits such as skin color among controls, notably for rs1042522 and rs861539. This insight underscores the importance of considering racial and ethnic genetic backgrounds as modifiers in epidemiological studies and reinforces the necessity for population-specific genetic databases in cancer genomics.
The interplay between genetic predisposition and environmental factors was further elucidated through the interaction analyses. For instance, the combined effect of rs25487 and cigarette smoking dramatically amplified lung cancer risk, illustrating how genetic vulnerability may compound the detrimental effects of tobacco carcinogens. This synergy attained statistical significance with an OR of 3.72 and a strong p-interaction value, emphasizing smoking cessation as an indispensable intervention even in genetically predisposed individuals.
Furthermore, the study unearthed a borderline significant interaction between alcohol consumption and the variant rs13181, hinting at a possible protective modification against lung cancer risk. Although the p-interaction remained slightly above strict thresholds, this finding prompts further exploration into lifestyle-genetic interplay and its mechanistic basis within DNA repair pathways.
Apart from susceptibility, the research delved into survival outcomes, assessing the impact of these polymorphisms on overall patient prognosis. Intriguingly, the alternative allele of rs11016879 emerged as an independent prognostic factor associated with increased 5-year survival rates among lung cancer patients. This polymorphism, residing in the ERCC2 gene vital for nucleotide excision repair, may enhance repair efficiency post-diagnosis or influence treatment responsiveness, representing a potential biomarker for patient stratification.
The methodological approach of the study incorporated robust statistical techniques including logistic regression for association testing and survival analyses through Kaplan-Meier and Cox regression models. These quantitative frameworks enabled precise estimation of genetic effects while accounting for covariates such as demographic factors and lifestyle exposures, thereby strengthening the validity of the conclusions.
This study breaks new ground by providing the first comprehensive evaluation of DNA repair gene variants in relation to lung cancer risk and survival within a Cuban cohort. The findings accentuate the heterogeneity of genetic risk factors across populations and emphasize the critical role of incorporating ancestral genetic diversity and phenotypic attributes like skin color in cancer susceptibility research.
In the context of public health, these insights have profound implications. They call for tailored screening programs incorporating genetic risk profiles alongside environmental exposure assessments, particularly targeting high-risk groups identified by combined genetic and lifestyle factors. Moreover, such knowledge could inform personalized therapeutic strategies, optimizing treatment choices based on individual genetic repair capacity.
The research also highlights the pressing need for further explorations into how polymorphisms in DNA repair genes interact with complex environmental carcinogens, including tobacco and alcohol, under diverse genetic backgrounds. Such studies are essential for unraveling the multifactorial nature of lung cancer development and progression.
As lung cancer continues to impose a massive global health burden, especially in regions with high smoking prevalence and genetic admixture like Cuba, this investigation sets a valuable precedent. It demonstrates that genetic epidemiology, when integrated thoughtfully with population characteristics, can provide actionable insights for early detection, prevention, and clinical management.
Ultimately, this investigation into the Cuban population underscores how the convergence of genetic polymorphisms and environmental exposures orchestrate lung cancer risk and outcomes. It is a clarion call for expanding genomic research across diverse populations, moving beyond European-centric studies, to achieve equitable advancements in cancer care worldwide.
The study’s novel findings herald a new era for cancer genetics in Latin America, paving the way for personalized medicine approaches grounded in the molecular landscape of populations historically underrepresented in research. As more comprehensive genetic and environmental data are accumulated, the hope is to translate these discoveries into tangible clinical benefits, improving survival and quality of life for lung cancer patients everywhere.
Subject of Research: Genetic polymorphisms in DNA repair related genes and their association with lung cancer susceptibility and survival prognosis in the Cuban population
Article Title: Polymorphisms in DNA repair related genes as risk factors for lung cancer in Cuban population: a case control study
Article References:
Reyes-Reyes, E., Cuétara-Lugo, E., Herrera-Isidrón, J.A. et al. Polymorphisms in DNA repair related genes as risk factors for lung cancer in Cuban population: a case control study. BMC Cancer 25, 1717 (2025). https://doi.org/10.1186/s12885-025-15072-1
Image Credits: Scienmag.com
DOI: 10.1186/s12885-025-15072-1
