Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Nikhil K. Khankari; Xiao Ou Shu; Wanqing Wen; Peter Kraft; Sara Lindström; Ulrike Peters; Joellen Schildkraut; Fredrick Schumacher; Paolo Bofetta; Angela Risch; Heike Bickeböller; Christopher I. Amos; Douglas Easton; Rosalind A. Eeles; Stephen B. Gruber; Christopher A. Haiman; David J. Hunter; Stephen J. Chanock; Brandon L. Pierce; Wei Zheng; Kendra Blalock; Peter T. Campbell; Graham Casey; David V. Conti; Christopher K. Edlund; Jane Figueiredo; W. James Gauderman; Jian Gong; Roger C. Green; John F. Harju; Tabitha A. Harrison; Eric J. Jacobs; Mark A. Jenkins; Shuo Jiao; Li Li; Yi Lin; Frank J. Manion; Victor Moreno; Bhramar Mukherjee; Leon Raskin; Fredrick R. Schumacher; Daniela Seminara; Gianluca Severi; Stephanie L. Stenzel; Duncan C. Thomas; John L. Hopper; Melissa C. Southey; Enes Makalic; Daniel F. Schmidt; Olivia Fletcher; Julian Peto; Lorna Gibson; Isabel dos Santos Silva; Habib Ahsan; Alice Whittemore; Quinten Waisfisz; Hanne Meijers-Heijboer; Muriel Adank; Rob B. van der Luijt; Andre G. Uitterlinden; Albert Hofman; Alfons Meindl; Rita K. Schmutzler; Bertram Müller-Myhsok; Peter Lichtner; Heli Nevanlinna; Taru A. Muranen; Kristiina Aittomäki; Carl Blomqvist; Jenny Chang-Claude; Rebecca Hein; Norbert Dahmen; Lars Beckman; Laura Crisponi; Per Hall; Kamila Czene; Astrid Irwanto; Jianjun Liu; Douglas F. Easton; Clare Turnbull; Nazneen Rahman; Rosalind Eeles; Zsofia Kote-Jarai; Kenneth Muir; Graham Giles; David Neal; Jenny L. Donovan; Freddie C. Hamdy; Fredrik Wiklund; Henrik Gronberg; Christopher Haiman; Fred Schumacher; Ruth Travis; Elio Riboli; David Hunter; Susan Gapstur; Sonja Berndt; Stephen Chanock; Younghun Han; Li Su; Yongyue Wei; Rayjean J. Hung; Yonathan Brhane; John McLaughlin; Paul Brennan; James D. McKay; Albert Rosenberger; Richard S. Houlston; Neil Caporaso; Maria Teresa Landi; Joachim Heinrich; Xifeng Wu; Yuanqing Ye; David C. Christiani

doi:https://doi.org/10.1371/journal.pmed.1002118

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Nikhil K. Khankari, Xiao Ou Shu, Wanqing Wen, Peter Kraft, Sara Lindström, Ulrike Peters, Joellen Schildkraut, Fredrick Schumacher, Paolo Bofetta, Angela Risch, Heike Bickeböller, Christopher I. Amos, Douglas Easton, Rosalind A. Eeles, Stephen B. Gruber, Christopher A. Haiman, David J. Hunter, Stephen J. Chanock, Brandon L. Pierce, Wei ZhengKendra Blalock, Peter T. Campbell, Graham Casey, David V. Conti, Christopher K. Edlund, Jane Figueiredo, W. James Gauderman, Jian Gong, Roger C. Green, John F. Harju, Tabitha A. Harrison, Eric J. Jacobs, Mark A. Jenkins, Shuo Jiao, Li Li, Yi Lin, Frank J. Manion, Victor Moreno, Bhramar Mukherjee, Leon Raskin, Fredrick R. Schumacher, Daniela Seminara, Gianluca Severi, Stephanie L. Stenzel, Duncan C. Thomas, John L. Hopper, Melissa C. Southey, Enes Makalic, Daniel F. Schmidt, Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel dos Santos Silva, Habib Ahsan, Alice Whittemore, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel Adank, Rob B. van der Luijt, Andre G. Uitterlinden, Albert Hofman, Alfons Meindl, Rita K. Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Jenny Chang-Claude, Rebecca Hein, Norbert Dahmen, Lars Beckman, Laura Crisponi, Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu, Douglas F. Easton, Clare Turnbull, Nazneen Rahman, Rosalind Eeles, Zsofia Kote-Jarai, Kenneth Muir, Graham Giles, David Neal, Jenny L. Donovan, Freddie C. Hamdy, Fredrik Wiklund, Henrik Gronberg, Christopher Haiman, Fred Schumacher, Ruth Travis, Elio Riboli, David Hunter, Susan Gapstur, Sonja Berndt, Stephen Chanock, Younghun Han, Li Su, Yongyue Wei, Rayjean J. Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, James D. McKay, Albert Rosenberger, Richard S. Houlston, Neil Caporaso, Maria Teresa Landi, Joachim Heinrich, Xifeng Wu, Yuanqing Ye, David C. Christiani

Human Genetics (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

62 Citations (Scopus)

Abstract

Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

Original language	English
Article number	e1002118
Journal	PLoS medicine
Volume	13
Issue number	9
DOIs	https://doi.org/10.1371/journal.pmed.1002118
Publication status	Published - 1 Sept 2016

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https://doi.org/10.1371/journal.pmed.1002118

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Khankari, N. K., Shu, X. O., Wen, W., Kraft, P., Lindström, S., Peters, U., Schildkraut, J., Schumacher, F., Bofetta, P., Risch, A., Bickeböller, H., Amos, C. I., Easton, D., Eeles, R. A., Gruber, S. B., Haiman, C. A., Hunter, D. J., Chanock, S. J., Pierce, B. L., ... Christiani, D. C. (2016). Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses. PLoS medicine, 13(9), Article e1002118. https://doi.org/10.1371/journal.pmed.1002118

@article{53f8105e9ec04bb584ef2b8d98152873,

title = "Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses",

abstract = "Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.",

author = "Khankari, {Nikhil K.} and Shu, {Xiao Ou} and Wanqing Wen and Peter Kraft and Sara Lindstr{\"o}m and Ulrike Peters and Joellen Schildkraut and Fredrick Schumacher and Paolo Bofetta and Angela Risch and Heike Bickeb{\"o}ller and Amos, {Christopher I.} and Douglas Easton and Eeles, {Rosalind A.} and Gruber, {Stephen B.} and Haiman, {Christopher A.} and Hunter, {David J.} and Chanock, {Stephen J.} and Pierce, {Brandon L.} and Wei Zheng and Kendra Blalock and Campbell, {Peter T.} and Graham Casey and Conti, {David V.} and Edlund, {Christopher K.} and Jane Figueiredo and {James Gauderman}, W. and Jian Gong and Green, {Roger C.} and Harju, {John F.} and Harrison, {Tabitha A.} and Jacobs, {Eric J.} and Jenkins, {Mark A.} and Shuo Jiao and Li Li and Yi Lin and Manion, {Frank J.} and Victor Moreno and Bhramar Mukherjee and Leon Raskin and Schumacher, {Fredrick R.} and Daniela Seminara and Gianluca Severi and Stenzel, {Stephanie L.} and Thomas, {Duncan C.} and Hopper, {John L.} and Southey, {Melissa C.} and Enes Makalic and Schmidt, {Daniel F.} and Olivia Fletcher and Julian Peto and Lorna Gibson and {dos Santos Silva}, Isabel and Habib Ahsan and Alice Whittemore and Quinten Waisfisz and Hanne Meijers-Heijboer and Muriel Adank and {van der Luijt}, {Rob B.} and Uitterlinden, {Andre G.} and Albert Hofman and Alfons Meindl and Schmutzler, {Rita K.} and Bertram M{\"u}ller-Myhsok and Peter Lichtner and Heli Nevanlinna and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Jenny Chang-Claude and Rebecca Hein and Norbert Dahmen and Lars Beckman and Laura Crisponi and Per Hall and Kamila Czene and Astrid Irwanto and Jianjun Liu and Easton, {Douglas F.} and Clare Turnbull and Nazneen Rahman and Rosalind Eeles and Zsofia Kote-Jarai and Kenneth Muir and Graham Giles and David Neal and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Fredrik Wiklund and Henrik Gronberg and Christopher Haiman and Fred Schumacher and Ruth Travis and Elio Riboli and David Hunter and Susan Gapstur and Sonja Berndt and Stephen Chanock and Younghun Han and Li Su and Yongyue Wei and Hung, {Rayjean J.} and Yonathan Brhane and John McLaughlin and Paul Brennan and McKay, {James D.} and Albert Rosenberger and Houlston, {Richard S.} and Neil Caporaso and {Teresa Landi}, Maria and Joachim Heinrich and Xifeng Wu and Yuanqing Ye and Christiani, {David C.}",

year = "2016",

month = sep,

day = "1",

doi = "https://doi.org/10.1371/journal.pmed.1002118",

language = "English",

volume = "13",

journal = "PLoS medicine",

issn = "1549-1277",

publisher = "Nature Publishing Group",

number = "9",

}

Khankari, NK, Shu, XO, Wen, W, Kraft, P, Lindström, S, Peters, U, Schildkraut, J, Schumacher, F, Bofetta, P, Risch, A, Bickeböller, H, Amos, CI, Easton, D, Eeles, RA, Gruber, SB, Haiman, CA, Hunter, DJ, Chanock, SJ, Pierce, BL, Zheng, W, Blalock, K, Campbell, PT, Casey, G, Conti, DV, Edlund, CK, Figueiredo, J, James Gauderman, W, Gong, J, Green, RC, Harju, JF, Harrison, TA, Jacobs, EJ, Jenkins, MA, Jiao, S, Li, L, Lin, Y, Manion, FJ, Moreno, V, Mukherjee, B, Raskin, L, Schumacher, FR, Seminara, D, Severi, G, Stenzel, SL, Thomas, DC, Hopper, JL, Southey, MC, Makalic, E, Schmidt, DF, Fletcher, O, Peto, J, Gibson, L, dos Santos Silva, I, Ahsan, H, Whittemore, A, Waisfisz, Q , Meijers-Heijboer, H, Adank, M, van der Luijt, RB, Uitterlinden, AG, Hofman, A, Meindl, A, Schmutzler, RK, Müller-Myhsok, B, Lichtner, P, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Chang-Claude, J, Hein, R, Dahmen, N, Beckman, L, Crisponi, L, Hall, P, Czene, K, Irwanto, A, Liu, J, Easton, DF, Turnbull, C, Rahman, N, Eeles, R, Kote-Jarai, Z, Muir, K, Giles, G, Neal, D, Donovan, JL, Hamdy, FC, Wiklund, F, Gronberg, H, Haiman, C, Schumacher, F, Travis, R, Riboli, E, Hunter, D, Gapstur, S, Berndt, S, Chanock, S, Han, Y, Su, L, Wei, Y, Hung, RJ, Brhane, Y, McLaughlin, J, Brennan, P, McKay, JD, Rosenberger, A, Houlston, RS, Caporaso, N, Teresa Landi, M, Heinrich, J, Wu, X, Ye, Y & Christiani, DC 2016, 'Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses', PLoS medicine, vol. 13, no. 9, e1002118. https://doi.org/10.1371/journal.pmed.1002118

TY - JOUR

T1 - Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer

T2 - Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

AU - Khankari, Nikhil K.

AU - Shu, Xiao Ou

AU - Wen, Wanqing

AU - Kraft, Peter

AU - Lindström, Sara

AU - Peters, Ulrike

AU - Schildkraut, Joellen

AU - Schumacher, Fredrick

AU - Bofetta, Paolo

AU - Risch, Angela

AU - Bickeböller, Heike

AU - Amos, Christopher I.

AU - Easton, Douglas

AU - Eeles, Rosalind A.

AU - Gruber, Stephen B.

AU - Haiman, Christopher A.

AU - Hunter, David J.

AU - Chanock, Stephen J.

AU - Pierce, Brandon L.

AU - Zheng, Wei

AU - Blalock, Kendra

AU - Campbell, Peter T.

AU - Casey, Graham

AU - Conti, David V.

AU - Edlund, Christopher K.

AU - Figueiredo, Jane

AU - James Gauderman, W.

AU - Gong, Jian

AU - Green, Roger C.

AU - Harju, John F.

AU - Harrison, Tabitha A.

AU - Jacobs, Eric J.

AU - Jenkins, Mark A.

AU - Jiao, Shuo

AU - Li, Li

AU - Lin, Yi

AU - Manion, Frank J.

AU - Moreno, Victor

AU - Mukherjee, Bhramar

AU - Raskin, Leon

AU - Schumacher, Fredrick R.

AU - Seminara, Daniela

AU - Severi, Gianluca

AU - Stenzel, Stephanie L.

AU - Thomas, Duncan C.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Fletcher, Olivia

AU - Peto, Julian

AU - Gibson, Lorna

AU - dos Santos Silva, Isabel

AU - Ahsan, Habib

AU - Whittemore, Alice

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Adank, Muriel

AU - van der Luijt, Rob B.

AU - Uitterlinden, Andre G.

AU - Hofman, Albert

AU - Meindl, Alfons

AU - Schmutzler, Rita K.

AU - Müller-Myhsok, Bertram

AU - Lichtner, Peter

AU - Nevanlinna, Heli

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Dahmen, Norbert

AU - Beckman, Lars

AU - Crisponi, Laura

AU - Hall, Per

AU - Czene, Kamila

AU - Irwanto, Astrid

AU - Liu, Jianjun

AU - Easton, Douglas F.

AU - Turnbull, Clare

AU - Rahman, Nazneen

AU - Eeles, Rosalind

AU - Kote-Jarai, Zsofia

AU - Muir, Kenneth

AU - Giles, Graham

AU - Neal, David

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Wiklund, Fredrik

AU - Gronberg, Henrik

AU - Haiman, Christopher

AU - Schumacher, Fred

AU - Travis, Ruth

AU - Riboli, Elio

AU - Hunter, David

AU - Gapstur, Susan

AU - Berndt, Sonja

AU - Chanock, Stephen

AU - Han, Younghun

AU - Su, Li

AU - Wei, Yongyue

AU - Hung, Rayjean J.

AU - Brhane, Yonathan

AU - McLaughlin, John

AU - Brennan, Paul

AU - McKay, James D.

AU - Rosenberger, Albert

AU - Houlston, Richard S.

AU - Caporaso, Neil

AU - Teresa Landi, Maria

AU - Heinrich, Joachim

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - Christiani, David C.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

AB - Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

UR - http://www.scopus.com/inward/record.url?scp=84989836123&partnerID=8YFLogxK

U2 - https://doi.org/10.1371/journal.pmed.1002118

DO - https://doi.org/10.1371/journal.pmed.1002118

M3 - Article

C2 - 27598322

SN - 1549-1277

VL - 13

JO - PLoS medicine

JF - PLoS medicine

IS - 9

M1 - e1002118

ER -

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

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