Abstract 2267: A prospective assessment for telomere length in relation to risk of cancer in the Singapore Chinese Health Study

Abstract

Abstract Background: Telomeres are crucial in the maintenance of chromosome integrity and genomic stability. A critically short telomere length can trigger cell to enter replicative senescence with a result of cell death; alternatively, cells continue to divide if death does not occur, which results in genomic instability and chromosomal abnormality. A series of epidemiological studies have examined the association between telomere length and the risk of cancers, but the findings remain conflicting. 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 from 1993 through 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 24,847 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 =1,464). As of December 31, 2015, 3,778 participants developed cancer, including 722 colorectal cancer, 599 lung cancer, and 412 breast cancer. Cox models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing any cancer and these selected specific cancer types for different quintiles of TSR. Results: Women had a 5.7% higher TSR value than men (P<0.0001). Age, level of education, number of cigarettes/day, years of smoking, and pack-years of smoking were all inversely associated with TSR (P<0.0001). High TSR was associated, in a dose-dependent manner, with significantly increased risk of total cancer and breast, colorectal and lung cancer. Compared with the lowest quintile, the HRs (95% CIs) of total cancer for the 2nd, 3rd, and 4th, and 5th quintile of TSR were 1.03 (0.89, 1.20), 1.08 (0.93-1.26), 1.15 (0.98-1.34), and 1.36 (1.16-1.58), respectively, after adjustment for age, sex, education and smoking (Ptrend=0.001). The corresponding HRs (95% CIs) were 1.21 (0.72-2.03), 1.59 (0.97-2.60), 1.59 (1.04-2.75) and 1.62 (0.99-2.66) for breast cancer (Ptrend=0.023); 1.44 (1.03-2.00), 1.10 (0.76-1.59), 1.32 (0.92-1.90) and 1.88 (1.32-2.66) for colorectal cancer (Ptrend=0.004); and 1.41 (0.98-2.05), 1.37 (0.93-2.02), 1.31 (0.86-1.99) and 1.88 (1.26-2.81) for lung cancer (Ptrend=0.010). Conclusions: This prospective cohort study demonstrates that longer telomere length is associated with significantly increased risk of total and major cancers in a general population. These results suggest a complex role of telomere in the development of cancer. Citation Format: Jian-Min Yuan, Renwei Wang, Kenneth Beckman, Aizhen Jin, Woon-Puay Koh. A prospective assessment for telomere length in relation to risk of cancer in 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 2267. doi:10.1158/1538-7445.AM2017-2267