The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population

Background: Telomere length is associated with cancer as well as aging.  Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging.  Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk. Materials and Methods: This case-control study consists of 462 lung cancer cases and 379 controls from Japan.  We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer.  Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14–0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02–5.87) but the OR for interaction was in the opposite direction. Conclusions: Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.