Genetic Variation in BCL2 3′-UTR Was Associated with Lung Cancer Risk and Prognosis in Male Chinese Population

Abstract

ObjectivesBcl-2 is a critical apoptosis inhibitor with established carcinogenic potential, and can confer cancer cell resistance to therapeutic treatments by activating anti-apoptotic cellular defense. We hypothesized that genetic variants of BCL2 gene may be associated with lung cancer susceptibility and prognosis.MethodsThree selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483) were genotyped in 1017 paired male Chinese lung cancer cases and controls by TaqMan assay. The associations of these variants with risk of lung cancer and overall survival of 242 male advanced non-small-cell lung cancer (NSCLC) patients were separately investigated.ResultsCompared with the BCL2 3′UTR rs1564483GG genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with significantly decreased susceptibilities of lung cancer in male Chinese (adjusted OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively), while rs1564483A allele has a inverse dose-response relationship with lung cancer risk (P trend = 0.010). These effects were more evident in the elders, smokers, and subjects without family history of cancer (P trend = 0.017, 0.043 and 0.005, respectively). Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA genotypes had significantly longer median survival time (Long-rank P = 0.036) and decreased death risk (adjusted HR = 0.69, P = 0.027) than patients with rs1564483GG genotype. These effects were more obvious in patients with smoking, stage IIIA, and in patients without surgery but underwent chemotherapy or radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all P<0.05).ConclusionThe BCL2 3′UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes.

Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC

“…The expression of Bcl-2 may serve as predictive biomarker of response to induction chemotherapy in HNSCC (head and neck squamous cell carcinomas) patients (23). The genetic variation in Bcl-2 3'-uTR was associated with a decreased lung cancer risk and better survival for non-small cell lung cancer in male Chinese (24). Overexpression of Bcl-2 protein predicts chemoresistance in acute myeloid leukemia (25).…”

MicroRNA binding site polymorphisms as biomarkers in cancer management and research

“…Another study provided the evidence that the rs1564483 A allele, located within the 3′-UTR of BCL2 , was associated with a significantly lower risk for LC in male Chinese patients and with a favorable OS in advanced NSCLC patients 29. This effect was more obvious in smoking patients, in stage IIIA patients, and in patients without surgery undergone to chemotherapy or radiotherapy.…”

“…This effect was more obvious in smoking patients, in stage IIIA patients, and in patients without surgery undergone to chemotherapy or radiotherapy. The authors speculated that the rs1564483 G-to-A substitution might change the stem-loop structure of 3′-UTR or introduce a miRNA binding site, which may affect BCL2 mRNA stability or its expression levels 29. Several miRNAs, including miR-181b,30 miR-200bc/429,31 and miR-204,32 have been reported to bind to the BCL2 3′-UTR in correspondence with the miRSNP, thereby modulating BCL2 mRNA levels.…”

Role of Bcl-2 -938 C>A polymorphism in susceptibility and prognosis of cancer: a meta-analysis

“…Zhang et al reported that Bcl-2 -938C>A polymorphism may be relevant to the clinical symptoms of major depressive disorder15. Recently, several studies have reported that Bcl-2 -938C>A promoter polymorphism is associated with susceptibility and prognosis of cancer161718192021222324252627282930313233343536373839.…”