Imperial College London
Alternate

ProfessorPaoloVineis

Faculty of Medicine, School of Public Health

Chair in Environmental Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3372p.vineis Website

 
 
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Location

 

511Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kachuri:2019:ije/dyy140,
author = {Kachuri, L and Saarela, O and Bojesen, SE and Davey, Smith G and Liu, G and Landi, MT and Caporaso, NE and Christiani, DC and Johansson, M and Panico, S and Overvad, K and Trichopoulou, A and Vineis, P and Scelo, G and Zaridze, D and Wu, X and Albanes, D and Diergaarde, B and Lagiou, P and Macfarlane, GJ and Aldrich, MC and Tardón, A and Rennert, G and Olshan, AF and Weissler, MC and Chen, C and Goodman, GE and Doherty, JA and Ness, AR and Bickeböller, H and Wichmann, H-E and Risch, A and Field, JK and Teare, MD and Kiemeney, LA and van, der Heijden EHFM and Carroll, JC and Haugen, A and Zienolddiny, S and Skaug, V and Wünsch-Filho, V and Tajara, EH and Ayoub, Moysés R and Daumas, Nunes F and Lam, S and Eluf-Neto, J and Lacko, M and Peters, WHM and Le, Marchand L and Duell, EJ and Andrew, AS and Franceschi, S and Schabath, MB and Manjer, J and Arnold, S and Lazarus, P and Mukeriya, A and Swiatkowska, B and Janout, V and Holcatova, I and Stojsic, J and Mates, D and Lissowska, J and Bocc},
doi = {ije/dyy140},
journal = {International Journal of Epidemiology},
pages = {751--766},
title = {Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers},
url = {http://dx.doi.org/10.1093/ije/dyy140},
volume = {48},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.
AU  - Kachuri,L
AU  - Saarela,O
AU  - Bojesen,SE
AU  - Davey,Smith G
AU  - Liu,G
AU  - Landi,MT
AU  - Caporaso,NE
AU  - Christiani,DC
AU  - Johansson,M
AU  - Panico,S
AU  - Overvad,K
AU  - Trichopoulou,A
AU  - Vineis,P
AU  - Scelo,G
AU  - Zaridze,D
AU  - Wu,X
AU  - Albanes,D
AU  - Diergaarde,B
AU  - Lagiou,P
AU  - Macfarlane,GJ
AU  - Aldrich,MC
AU  - Tardón,A
AU  - Rennert,G
AU  - Olshan,AF
AU  - Weissler,MC
AU  - Chen,C
AU  - Goodman,GE
AU  - Doherty,JA
AU  - Ness,AR
AU  - Bickeböller,H
AU  - Wichmann,H-E
AU  - Risch,A
AU  - Field,JK
AU  - Teare,MD
AU  - Kiemeney,LA
AU  - van,der Heijden EHFM
AU  - Carroll,JC
AU  - Haugen,A
AU  - Zienolddiny,S
AU  - Skaug,V
AU  - Wünsch-Filho,V
AU  - Tajara,EH
AU  - Ayoub,Moysés R
AU  - Daumas,Nunes F
AU  - Lam,S
AU  - Eluf-Neto,J
AU  - Lacko,M
AU  - Peters,WHM
AU  - Le,Marchand L
AU  - Duell,EJ
AU  - Andrew,AS
AU  - Franceschi,S
AU  - Schabath,MB
AU  - Manjer,J
AU  - Arnold,S
AU  - Lazarus,P
AU  - Mukeriya,A
AU  - Swiatkowska,B
AU  - Janout,V
AU  - Holcatova,I
AU  - Stojsic,J
AU  - Mates,D
AU  - Lissowska,J
AU  - Boccia,S
AU  - Lesseur,C
AU  - Zong,X
AU  - McKay,JD
AU  - Brennan,P
AU  - Amos,CI
AU  - Hung,RJ
DO  - ije/dyy140
EP  - 766
PY  - 2019///
SN  - 1464-3685
SP  - 751
TI  - Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers
T2  - International Journal of Epidemiology
UR  - http://dx.doi.org/10.1093/ije/dyy140
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30059977
UR  - http://hdl.handle.net/10044/1/61846
VL  - 48
ER  -
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