Telomere length and risk of developing gastric adenocarcinoma: The Singapore Chinese Health Study
- 116 Downloads
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.
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.
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.
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.
KeywordsGastric adenocarcinoma Telomere length Prospective cohort study
We thank Siew-Hong Low of the National University of Singapore for supervising the fieldwork of the Singapore Chinese Health Study and the Singapore Cancer Registry for assistance with the identification of cancer outcomes. This study was funded by National Institute of Health (NIH)/National Cancer Institute (NCI) Grant number: R01 CA144034 and UM1 CA182876 (to J.-M. Yuan). W-PK is supported by the National Medical Research Council, Singapore (NMRC/CSA/0055/2013).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all participants.
The Singapore Chinese Health Study was approved by the Institutional Review Boards at the National University of Singapore and the University of Pittsburgh (Pittsburgh, PA, USA).
- 12.Seow A, Shi CY, Chung FL, Jiao D, Hankin JH, Lee HP, et al. Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomark Prev. 1998;7(9):775–81.Google Scholar
- 14.Singapore Cancer Registry Interim Report. Trends in Cancer incidence in Singapore 2010–2014. May 26, 2015. https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/cancer-trends-2010-2014_interim-annual-report_final-(public)9efe07a5c9d76bafab5aff000014cdee.pdf?sfvrsn=0. Accessed 17 Feb 2016.
- 15.Forman DBF, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R, Ferlay J (eds) (2014) Cancer incidence in five continents. Vol. X. IARC Scientific Publication No. 164. Lyon: International Agency for Research on CancerGoogle Scholar
- 17.Yuan J-M, Beckman KB, Wang R, Bull C, Adams-Haduch J, Huang JY, et al. Leukocyte telomere length in relation to risk of lung adenocarcinoma incidence: findings from the Singapore Chinese Health Study. Int J Cancer (accepted)Google Scholar
- 19.Harrell FE, Lee KL. Verifying assumptions of the Cox proportional hazards model. In: Proceedings of the eleventh annual SAS user’s group international conference. Cary, NC: SAS Institute; 1986. p. 823–828.Google Scholar