Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer

Ying Bao, Jennifer Prescott, Chen Yuan, Mingfeng Zhang, Peter Kraft, Ana Babic, Vicente Morales-Oyarvide, Zhi Rong Qian, Julie E. Buring, Barbara B. Cochrane, J. Michael Gaziano, Edward L. Giovannucci, Jo Ann E Manson, Kimmie Ng, Shuji Ogino, Thomas E. Rohan, Howard D. Sesso, Meir J. Stampfer, Charles S. Fuchs, Immaculata De VivoLaufey T. Amundadottir, Brian M. Wolpin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. Design We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. Results Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). Conclusions Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.

Original languageEnglish (US)
JournalGut
DOIs
StateAccepted/In press - Oct 21 2016

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Telomerase
Telomere
Pancreatic Neoplasms
Leukocytes
Genes
Alleles
Single Nucleotide Polymorphism
Logistic Models
Telomere Shortening
Linkage Disequilibrium
Linear Models
Fasting
Carcinogenesis
Body Mass Index
Smoking
Parturition

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bao, Y., Prescott, J., Yuan, C., Zhang, M., Kraft, P., Babic, A., ... Wolpin, B. M. (Accepted/In press). Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. Gut. https://doi.org/10.1136/gutjnl-2016-312510

Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. / Bao, Ying; Prescott, Jennifer; Yuan, Chen; Zhang, Mingfeng; Kraft, Peter; Babic, Ana; Morales-Oyarvide, Vicente; Qian, Zhi Rong; Buring, Julie E.; Cochrane, Barbara B.; Gaziano, J. Michael; Giovannucci, Edward L.; Manson, Jo Ann E; Ng, Kimmie; Ogino, Shuji; Rohan, Thomas E.; Sesso, Howard D.; Stampfer, Meir J.; Fuchs, Charles S.; Vivo, Immaculata De; Amundadottir, Laufey T.; Wolpin, Brian M.

In: Gut, 21.10.2016.

Research output: Contribution to journalArticle

Bao, Y, Prescott, J, Yuan, C, Zhang, M, Kraft, P, Babic, A, Morales-Oyarvide, V, Qian, ZR, Buring, JE, Cochrane, BB, Gaziano, JM, Giovannucci, EL, Manson, JAE, Ng, K, Ogino, S, Rohan, TE, Sesso, HD, Stampfer, MJ, Fuchs, CS, Vivo, ID, Amundadottir, LT & Wolpin, BM 2016, 'Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer', Gut. https://doi.org/10.1136/gutjnl-2016-312510
Bao, Ying ; Prescott, Jennifer ; Yuan, Chen ; Zhang, Mingfeng ; Kraft, Peter ; Babic, Ana ; Morales-Oyarvide, Vicente ; Qian, Zhi Rong ; Buring, Julie E. ; Cochrane, Barbara B. ; Gaziano, J. Michael ; Giovannucci, Edward L. ; Manson, Jo Ann E ; Ng, Kimmie ; Ogino, Shuji ; Rohan, Thomas E. ; Sesso, Howard D. ; Stampfer, Meir J. ; Fuchs, Charles S. ; Vivo, Immaculata De ; Amundadottir, Laufey T. ; Wolpin, Brian M. / Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. In: Gut. 2016.
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title = "Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer",
abstract = "Objective Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. Design We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95{\%} CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. Results Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95{\%} CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95{\%} CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95{\%} CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95{\%} CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). Conclusions Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.",
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T1 - Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer

AU - Bao, Ying

AU - Prescott, Jennifer

AU - Yuan, Chen

AU - Zhang, Mingfeng

AU - Kraft, Peter

AU - Babic, Ana

AU - Morales-Oyarvide, Vicente

AU - Qian, Zhi Rong

AU - Buring, Julie E.

AU - Cochrane, Barbara B.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Manson, Jo Ann E

AU - Ng, Kimmie

AU - Ogino, Shuji

AU - Rohan, Thomas E.

AU - Sesso, Howard D.

AU - Stampfer, Meir J.

AU - Fuchs, Charles S.

AU - Vivo, Immaculata De

AU - Amundadottir, Laufey T.

AU - Wolpin, Brian M.

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Y1 - 2016/10/21

N2 - Objective Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. Design We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. Results Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). Conclusions Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.

AB - Objective Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. Design We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. Results Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). Conclusions Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.

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