Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk

PAGE, GECCO and CCFR consortia

Iona Cheng, Jonathan M. Kocarnik, Logan Dumitrescu, Noralane M. Lindor, Jenny Chang-Claude, Christy L. Avery, Christian P. Caberto, Shelly Ann Love, Martha L. Slattery, Andrew T. Chan, John A. Baron, Lucia A. Hindorff, Sungshim Lani Park, Fredrick R. Schumacher, Michael Hoffmeister, Peter Kraft, Anne M. Butler, David J. Duggan, Lifang Hou, Chris S. Carlson & 47 others Kristine R. Monroe, Yi Lin, Cara L. Carty, Sue Mann, Jing Ma, Edward L. Giovannucci, Charles S. Fuchs, Polly A. Newcomb, Mark A. Jenkins, John L. Hopper, Robert W. Haile, David V. Conti, Peter T. Campbell, John D. Potter, Bette J. Caan, Robert E. Schoen, Richard B. Hayes, Stephen J. Chanock, Sonja I. Berndt, Sebastien Küry, Stephane Bézieau, Jose Luis Ambite, Gowri Kumaraguruparan, Danielle M. Richardson, Robert J. Goodloe, Holli H. Dilks, Paxton Baker, Brent W. Zanke, Mathieu Lemire, Steven Gallinger, Li Hsu, Shuo Jiao, Tabitha A. Harrison, Daniela Seminara, Christopher A. Haiman, Charles Kooperberg, Lynne R. Wilkens, Carolyn M. Hutter, Emily White, Dana C. Crawford, Gerardo Heiss, Thomas J. Hudson, Hermann Brenner, William S. Bush, Graham Casey, Loïc Le Marchand, Ulrike Peters

Research output: Contribution to journalArticle

Abstract

Objective: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design: We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 -4 was used to determine statistical significance of the associations. Results: Two correlated SNPs - rs10090154 and rs4242382 - in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10-5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

Original languageEnglish (US)
Pages (from-to)800-807
Number of pages8
JournalGut
Volume63
Issue number5
DOIs
StatePublished - May 1 2014
Externally publishedYes

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Molecular Epidemiology
Genomics
Colonic Neoplasms
Registries
Colorectal Neoplasms
Epidemiology
Single Nucleotide Polymorphism
Population
Neoplasms
Chromosomes, Human, Pair 1
Meta-Analysis
Genome-Wide Association Study
Prostatic Neoplasms
Logistic Models

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Cheng, I., Kocarnik, J. M., Dumitrescu, L., Lindor, N. M., Chang-Claude, J., Avery, C. L., ... Peters, U. (2014). Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia. Gut, 63(5), 800-807. https://doi.org/10.1136/gutjnl-2013-305189

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk : PAGE, GECCO and CCFR consortia. / Cheng, Iona; Kocarnik, Jonathan M.; Dumitrescu, Logan; Lindor, Noralane M.; Chang-Claude, Jenny; Avery, Christy L.; Caberto, Christian P.; Love, Shelly Ann; Slattery, Martha L.; Chan, Andrew T.; Baron, John A.; Hindorff, Lucia A.; Park, Sungshim Lani; Schumacher, Fredrick R.; Hoffmeister, Michael; Kraft, Peter; Butler, Anne M.; Duggan, David J.; Hou, Lifang; Carlson, Chris S.; Monroe, Kristine R.; Lin, Yi; Carty, Cara L.; Mann, Sue; Ma, Jing; Giovannucci, Edward L.; Fuchs, Charles S.; Newcomb, Polly A.; Jenkins, Mark A.; Hopper, John L.; Haile, Robert W.; Conti, David V.; Campbell, Peter T.; Potter, John D.; Caan, Bette J.; Schoen, Robert E.; Hayes, Richard B.; Chanock, Stephen J.; Berndt, Sonja I.; Küry, Sebastien; Bézieau, Stephane; Ambite, Jose Luis; Kumaraguruparan, Gowri; Richardson, Danielle M.; Goodloe, Robert J.; Dilks, Holli H.; Baker, Paxton; Zanke, Brent W.; Lemire, Mathieu; Gallinger, Steven; Hsu, Li; Jiao, Shuo; Harrison, Tabitha A.; Seminara, Daniela; Haiman, Christopher A.; Kooperberg, Charles; Wilkens, Lynne R.; Hutter, Carolyn M.; White, Emily; Crawford, Dana C.; Heiss, Gerardo; Hudson, Thomas J.; Brenner, Hermann; Bush, William S.; Casey, Graham; Le Marchand, Loïc; Peters, Ulrike.

In: Gut, Vol. 63, No. 5, 01.05.2014, p. 800-807.

Research output: Contribution to journalArticle

Cheng, I, Kocarnik, JM, Dumitrescu, L, Lindor, NM, Chang-Claude, J, Avery, CL, Caberto, CP, Love, SA, Slattery, ML, Chan, AT, Baron, JA, Hindorff, LA, Park, SL, Schumacher, FR, Hoffmeister, M, Kraft, P, Butler, AM, Duggan, DJ, Hou, L, Carlson, CS, Monroe, KR, Lin, Y, Carty, CL, Mann, S, Ma, J, Giovannucci, EL, Fuchs, CS, Newcomb, PA, Jenkins, MA, Hopper, JL, Haile, RW, Conti, DV, Campbell, PT, Potter, JD, Caan, BJ, Schoen, RE, Hayes, RB, Chanock, SJ, Berndt, SI, Küry, S, Bézieau, S, Ambite, JL, Kumaraguruparan, G, Richardson, DM, Goodloe, RJ, Dilks, HH, Baker, P, Zanke, BW, Lemire, M, Gallinger, S, Hsu, L, Jiao, S, Harrison, TA, Seminara, D, Haiman, CA, Kooperberg, C, Wilkens, LR, Hutter, CM, White, E, Crawford, DC, Heiss, G, Hudson, TJ, Brenner, H, Bush, WS, Casey, G, Le Marchand, L & Peters, U 2014, 'Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia', Gut, vol. 63, no. 5, pp. 800-807. https://doi.org/10.1136/gutjnl-2013-305189
Cheng, Iona ; Kocarnik, Jonathan M. ; Dumitrescu, Logan ; Lindor, Noralane M. ; Chang-Claude, Jenny ; Avery, Christy L. ; Caberto, Christian P. ; Love, Shelly Ann ; Slattery, Martha L. ; Chan, Andrew T. ; Baron, John A. ; Hindorff, Lucia A. ; Park, Sungshim Lani ; Schumacher, Fredrick R. ; Hoffmeister, Michael ; Kraft, Peter ; Butler, Anne M. ; Duggan, David J. ; Hou, Lifang ; Carlson, Chris S. ; Monroe, Kristine R. ; Lin, Yi ; Carty, Cara L. ; Mann, Sue ; Ma, Jing ; Giovannucci, Edward L. ; Fuchs, Charles S. ; Newcomb, Polly A. ; Jenkins, Mark A. ; Hopper, John L. ; Haile, Robert W. ; Conti, David V. ; Campbell, Peter T. ; Potter, John D. ; Caan, Bette J. ; Schoen, Robert E. ; Hayes, Richard B. ; Chanock, Stephen J. ; Berndt, Sonja I. ; Küry, Sebastien ; Bézieau, Stephane ; Ambite, Jose Luis ; Kumaraguruparan, Gowri ; Richardson, Danielle M. ; Goodloe, Robert J. ; Dilks, Holli H. ; Baker, Paxton ; Zanke, Brent W. ; Lemire, Mathieu ; Gallinger, Steven ; Hsu, Li ; Jiao, Shuo ; Harrison, Tabitha A. ; Seminara, Daniela ; Haiman, Christopher A. ; Kooperberg, Charles ; Wilkens, Lynne R. ; Hutter, Carolyn M. ; White, Emily ; Crawford, Dana C. ; Heiss, Gerardo ; Hudson, Thomas J. ; Brenner, Hermann ; Bush, William S. ; Casey, Graham ; Le Marchand, Loïc ; Peters, Ulrike. / Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk : PAGE, GECCO and CCFR consortia. In: Gut. 2014 ; Vol. 63, No. 5. pp. 800-807.
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title = "Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia",
abstract = "Objective: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design: We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 -4 was used to determine statistical significance of the associations. Results: Two correlated SNPs - rs10090154 and rs4242382 - in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95{\%} CI 1.07 to 1.18; p=1.74×10-5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.",
author = "Iona Cheng and Kocarnik, {Jonathan M.} and Logan Dumitrescu and Lindor, {Noralane M.} and Jenny Chang-Claude and Avery, {Christy L.} and Caberto, {Christian P.} and Love, {Shelly Ann} and Slattery, {Martha L.} and Chan, {Andrew T.} and Baron, {John A.} and Hindorff, {Lucia A.} and Park, {Sungshim Lani} and Schumacher, {Fredrick R.} and Michael Hoffmeister and Peter Kraft and Butler, {Anne M.} and Duggan, {David J.} and Lifang Hou and Carlson, {Chris S.} and Monroe, {Kristine R.} and Yi Lin and Carty, {Cara L.} and Sue Mann and Jing Ma and Giovannucci, {Edward L.} and Fuchs, {Charles S.} and Newcomb, {Polly A.} and Jenkins, {Mark A.} and Hopper, {John L.} and Haile, {Robert W.} and Conti, {David V.} and Campbell, {Peter T.} and Potter, {John D.} and Caan, {Bette J.} and Schoen, {Robert E.} and Hayes, {Richard B.} and Chanock, {Stephen J.} and Berndt, {Sonja I.} and Sebastien K{\"u}ry and Stephane B{\'e}zieau and Ambite, {Jose Luis} and Gowri Kumaraguruparan and Richardson, {Danielle M.} and Goodloe, {Robert J.} and Dilks, {Holli H.} and Paxton Baker and Zanke, {Brent W.} and Mathieu Lemire and Steven Gallinger and Li Hsu and Shuo Jiao and Harrison, {Tabitha A.} and Daniela Seminara and Haiman, {Christopher A.} and Charles Kooperberg and Wilkens, {Lynne R.} and Hutter, {Carolyn M.} and Emily White and Crawford, {Dana C.} and Gerardo Heiss and Hudson, {Thomas J.} and Hermann Brenner and Bush, {William S.} and Graham Casey and {Le Marchand}, Lo{\"i}c and Ulrike Peters",
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TY - JOUR

T1 - Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk

T2 - PAGE, GECCO and CCFR consortia

AU - Cheng, Iona

AU - Kocarnik, Jonathan M.

AU - Dumitrescu, Logan

AU - Lindor, Noralane M.

AU - Chang-Claude, Jenny

AU - Avery, Christy L.

AU - Caberto, Christian P.

AU - Love, Shelly Ann

AU - Slattery, Martha L.

AU - Chan, Andrew T.

AU - Baron, John A.

AU - Hindorff, Lucia A.

AU - Park, Sungshim Lani

AU - Schumacher, Fredrick R.

AU - Hoffmeister, Michael

AU - Kraft, Peter

AU - Butler, Anne M.

AU - Duggan, David J.

AU - Hou, Lifang

AU - Carlson, Chris S.

AU - Monroe, Kristine R.

AU - Lin, Yi

AU - Carty, Cara L.

AU - Mann, Sue

AU - Ma, Jing

AU - Giovannucci, Edward L.

AU - Fuchs, Charles S.

AU - Newcomb, Polly A.

AU - Jenkins, Mark A.

AU - Hopper, John L.

AU - Haile, Robert W.

AU - Conti, David V.

AU - Campbell, Peter T.

AU - Potter, John D.

AU - Caan, Bette J.

AU - Schoen, Robert E.

AU - Hayes, Richard B.

AU - Chanock, Stephen J.

AU - Berndt, Sonja I.

AU - Küry, Sebastien

AU - Bézieau, Stephane

AU - Ambite, Jose Luis

AU - Kumaraguruparan, Gowri

AU - Richardson, Danielle M.

AU - Goodloe, Robert J.

AU - Dilks, Holli H.

AU - Baker, Paxton

AU - Zanke, Brent W.

AU - Lemire, Mathieu

AU - Gallinger, Steven

AU - Hsu, Li

AU - Jiao, Shuo

AU - Harrison, Tabitha A.

AU - Seminara, Daniela

AU - Haiman, Christopher A.

AU - Kooperberg, Charles

AU - Wilkens, Lynne R.

AU - Hutter, Carolyn M.

AU - White, Emily

AU - Crawford, Dana C.

AU - Heiss, Gerardo

AU - Hudson, Thomas J.

AU - Brenner, Hermann

AU - Bush, William S.

AU - Casey, Graham

AU - Le Marchand, Loïc

AU - Peters, Ulrike

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Objective: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design: We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 -4 was used to determine statistical significance of the associations. Results: Two correlated SNPs - rs10090154 and rs4242382 - in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10-5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

AB - Objective: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design: We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 -4 was used to determine statistical significance of the associations. Results: Two correlated SNPs - rs10090154 and rs4242382 - in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10-5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

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U2 - 10.1136/gutjnl-2013-305189

DO - 10.1136/gutjnl-2013-305189

M3 - Article

VL - 63

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JO - Gut

JF - Gut

SN - 0017-5749

IS - 5

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