Zhensheng Wang1, Woon-Puay Koh2,3, Aizhen Jin4, Renwei Wang5, Jian-Min Yuan6,7. 1. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 2. Duke-NUS Medical School, Singapore, Singapore. 3. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. 4. National Registry of Diseases Office, Health Promotion Board, Singapore, Singapore. 5. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, 5150 Centre Avenue, Cancer Pavilion Suite 4C, Pittsburgh, 15232-1309, Pennsylvania, USA. 6. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. yuanj@upmc.edu. 7. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, 5150 Centre Avenue, Cancer Pavilion Suite 4C, Pittsburgh, 15232-1309, Pennsylvania, USA. yuanj@upmc.edu.
Abstract
BACKGROUND: Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager. METHODS: The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk. RESULTS: A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (P nonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals. CONCLUSIONS: This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis.
BACKGROUND: Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager. METHODS: The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk. RESULTS: A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (P nonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals. CONCLUSIONS: This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis.
Authors: Maren Weischer; Børge G Nordestgaard; Richard M Cawthon; Jacob J Freiberg; Anne Tybjærg-Hansen; Stig E Bojesen Journal: J Natl Cancer Inst Date: 2013-03-06 Impact factor: 13.506
Authors: Lynnette R Ferguson; Helen Chen; Andrew R Collins; Marisa Connell; Giovanna Damia; Santanu Dasgupta; Meenakshi Malhotra; Alan K Meeker; Amedeo Amedei; Amr Amin; S Salman Ashraf; Katia Aquilano; Asfar S Azmi; Dipita Bhakta; Alan Bilsland; Chandra S Boosani; Sophie Chen; Maria Rosa Ciriolo; Hiromasa Fujii; Gunjan Guha; Dorota Halicka; William G Helferich; W Nicol Keith; Sulma I Mohammed; Elena Niccolai; Xujuan Yang; Kanya Honoki; Virginia R Parslow; Satya Prakash; Sarallah Rezazadeh; Rodney E Shackelford; David Sidransky; Phuoc T Tran; Eddy S Yang; Christopher A Maxwell Journal: Semin Cancer Biol Date: 2015-04-11 Impact factor: 17.012