Abstract
BackgroundGenetic biomarkers of lung cancer (LC) susceptibility may provide a basis for treatment and prevention. This study analyzed an association between SNPs (single nucleotide polymorphisms) in the complementary region of the 3′-UTR (3′ untranslated region) of microRNAs of the gene RIPK1 (receptor-interacting serine/threonine-protein kinase 1) and LC among an adult Han Chinese population aged younger than 60 years. Also explored the effect of regulation of the RIPK1 gene via rs17548629 and microRNA-1197 on the occurrence of LC.MethodsRIPK1 variants (rs17548629, rs77736895) were determined in a population of 571 adults (younger than 60 years) with LC, and 609 gender- and age-matched healthy individuals. Bioinformatics methods predicted the microRNAs bound to rs17548629. Dual luciferase reporter assay was performed to confirm the presence of both rs17548629 and the predicted microRNA.ResultsA mutation (T) of rs17548629 was associated with an increased risk for LC in this population under the codominant and recessive genetic models. The risk of lung adenocarcinoma in rs17548629 mutant carriers was 1.769-fold higher than that of the wildtype. In vitro, the luciferase activity of co-transfected mutant psiCHECK2-RIPK1 and microRNA-1197 mimics was less than that of the group transfected with microRNA-1197 mimics only. Factorial analysis indicated interactions between microRNA-1197 mimics and genotypes of rs17548629.ConclusionA mutation (T) of rs17548629 may increase the risk of LC/lung adenocarcinoma in adult Han populations younger than 60 years. When carrying the T allele, rs17548629 may be the target of hsa-miR-1197. This mutation may affect transcriptional level of the RIPK1, thereby promoting the occurrence of LC.
Highlights
Genetic biomarkers of lung cancer (LC) susceptibility may provide a basis for treatment and prevention
The multi-classification logistic regression analysis showed that rs17548629 was associated with a significantly increased risk of lung adenocarcinoma under the recessive genetic model, but was not associated with an increased risk of other pathological types
This study found that a mutation (T) of RIPK1 rs17548629 was associated with a significantly increased risk of lung cancer in an adult population aged younger than 60 years, under the codominant and recessive genetic model, after adjustments for general demographic characteristics and environmental factors
Summary
Genetic biomarkers of lung cancer (LC) susceptibility may provide a basis for treatment and prevention. According to the 2018 GLOBOCAN statistics, lung cancer accounts for 11.6% of all morbidity worldwide, and ranks first among all deaths due to cancer (18.4%) [1]. In China, lung cancer has the highest morbidity and mortality. Yang et al Cancer Cell Int (2020) 20:143 of which were due to non-small cell lung cancer. Among the subtypes of non-small cell lung cancer, adenocarcinoma is more common than squamous cell carcinoma. Lung cancer is often diagnosed at an advanced stage (stage III or IV) and its 5-year survival rate is only 15%. The risk of lung cancer increases significantly in people older than 40 years, with maximum morbidity and mortality rates at 75 years [3]. It is highly important to explore the influencing factors and the mechanism of lung cancer
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