Abstract 2274: Extreme telomere length was associated with gastric adenocarcinoma risk: The Singapore Chinese Health Study

Abstract

Abstract Background: Evidence regarding extreme telomere length and increased gastric cancer risk has been limited in retrospective case-control study setting which was potentially subjected to selection bias and reverse causality. We conducted a prospective analysis in an Eastern Asian population to examine the hypothesis that extreme telomere length is associated with increased risk of gastric adenocarcinoma. Methods: Among 63,257 participants of the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women aged 45-74 years recruited between 1993 and 1998, 28,219 provided baseline blood samples. We used quantitative polymerase chain reaction (PCR) method to quantify relative telomere length determined by the ratio of telomere repeat copy number (T) to single-copy gene for albumin (S) (i.e., TSR) on all subjects. The present analysis included 24,846 subjects with valid TSR values after excluding samples with insufficient DNA (n = 1,908) and/or patients with prevalent cancer at baseline blood draw (n = 1,465). As of December 31, 2014, 191 study participants who were free of cancer developed gastric adenocarcinoma. The information on demographic and lifestyle characteristics was collected using structured questionnaires at baseline and two follow-up interviews. Cox proportional hazard regression method was used to estimate hazard ratio (HR) and the corresponding 95% confidence interval (CI) of developing gastric adenocarcinoma for different levels of decile TSR. Restricted cubic spline (RCS) analysis was applied to examine the nonlinear relationship between TSR level and gastric adenocarcinoma risk. Results: The RCS analysis revealed a U-shaped relationship between TSR and gastric adenocarcinoma risk (p-value for non-linear association=0.009). Compared with the 4th decile, HR (95% CI) for the lowest and highest deciles of TSR 2.27 (1.17-4.40) and 1.98 (0.95-4.13), respectively after adjusting for age, sex, education, interview year, dialect group and smoking status. Conclusions: This was the first prospective analysis of TSR and risk of developing gastric adenocarcinoma in a general population. The study demonstrates both extreme short and long telomere length to be associated with significantly increased risk of gastric adenocarcinoma. These results suggest a complex relationship between telomere length and gastric cancer risk. Citation Format: Zhensheng Wang, Woon-Puay Koh, Aizhen Jin, Renwei Wang, Jian-Min Yuan. Extreme telomere length was associated with gastric adenocarcinoma risk: The Singapore Chinese Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2274. doi:10.1158/1538-7445.AM2017-2274