CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk

Xabier Garcia-Albeniz, Anja Rudolph, Carolyn Hutter, Emily White, Yi Lin, Stephanie A. Rosse, Jane C. Figueiredo, Tabitha A. Harrison, Shuo Jiao, Hermann Brenner, Graham Casey, Thomas J. Hudson, Mark Thornquist, Loic Le Marchand, John Potter, Martha L. Slattery, Brent Zanke, John A. Baron, Bette J. Caan, Stephen J. ChanockSonja I. Berndt, Deanna Stelling, Charles S. Fuchs, Michael Hoffmeister, Katja Butterbach, Mengmeng Du, W. James Gauderman, Marc J. Gunter, Mathieu Lemire, Shuji Ogino, Jennifer Lin, Richard B. Hayes, Robert W. Haile, Robert E. Schoen, Greg S. Warnick, Mark A. Jenkins, Stephen N Thibodeau, Fredrick R. Schumacher, Noralane Morey Lindor, Laurence N. Kolonel, John L. Hopper, Jian Gong, Daniela Seminara, Bethann M. Pflugeisen, Cornelia M. Ulrich, Conghui Qu, David Duggan, Michelle Cotterchio, Peter T. Campbell, Christopher S. Carlson, Polly A. Newcomb, Edward Giovannucci, Li Hsu, Andrew T. Chan, Ulrike Peters, Jenny Chang-Claude

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background:Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods:We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test.Results:The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10 -9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10 -5 (alpha threshold=3.1 × 10 -4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively.Conclusions:Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalBritish Journal of Cancer
Volume114
Issue number2
DOIs
StatePublished - Jan 19 2016

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Progestins
Colorectal Neoplasms
Estrogens
Hormones
Therapeutics
Gene-Environment Interaction
Vitamin D
Logistic Models
Genotype
Vitamin D3 24-Hydroxylase
Genome
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Garcia-Albeniz, X., Rudolph, A., Hutter, C., White, E., Lin, Y., Rosse, S. A., ... Chang-Claude, J. (2016). CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. British Journal of Cancer, 114(2), 221-229. https://doi.org/10.1038/bjc.2015.443

CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. / Garcia-Albeniz, Xabier; Rudolph, Anja; Hutter, Carolyn; White, Emily; Lin, Yi; Rosse, Stephanie A.; Figueiredo, Jane C.; Harrison, Tabitha A.; Jiao, Shuo; Brenner, Hermann; Casey, Graham; Hudson, Thomas J.; Thornquist, Mark; Le Marchand, Loic; Potter, John; Slattery, Martha L.; Zanke, Brent; Baron, John A.; Caan, Bette J.; Chanock, Stephen J.; Berndt, Sonja I.; Stelling, Deanna; Fuchs, Charles S.; Hoffmeister, Michael; Butterbach, Katja; Du, Mengmeng; James Gauderman, W.; Gunter, Marc J.; Lemire, Mathieu; Ogino, Shuji; Lin, Jennifer; Hayes, Richard B.; Haile, Robert W.; Schoen, Robert E.; Warnick, Greg S.; Jenkins, Mark A.; Thibodeau, Stephen N; Schumacher, Fredrick R.; Lindor, Noralane Morey; Kolonel, Laurence N.; Hopper, John L.; Gong, Jian; Seminara, Daniela; Pflugeisen, Bethann M.; Ulrich, Cornelia M.; Qu, Conghui; Duggan, David; Cotterchio, Michelle; Campbell, Peter T.; Carlson, Christopher S.; Newcomb, Polly A.; Giovannucci, Edward; Hsu, Li; Chan, Andrew T.; Peters, Ulrike; Chang-Claude, Jenny.

In: British Journal of Cancer, Vol. 114, No. 2, 19.01.2016, p. 221-229.

Research output: Contribution to journalArticle

Garcia-Albeniz, X, Rudolph, A, Hutter, C, White, E, Lin, Y, Rosse, SA, Figueiredo, JC, Harrison, TA, Jiao, S, Brenner, H, Casey, G, Hudson, TJ, Thornquist, M, Le Marchand, L, Potter, J, Slattery, ML, Zanke, B, Baron, JA, Caan, BJ, Chanock, SJ, Berndt, SI, Stelling, D, Fuchs, CS, Hoffmeister, M, Butterbach, K, Du, M, James Gauderman, W, Gunter, MJ, Lemire, M, Ogino, S, Lin, J, Hayes, RB, Haile, RW, Schoen, RE, Warnick, GS, Jenkins, MA, Thibodeau, SN, Schumacher, FR, Lindor, NM, Kolonel, LN, Hopper, JL, Gong, J, Seminara, D, Pflugeisen, BM, Ulrich, CM, Qu, C, Duggan, D, Cotterchio, M, Campbell, PT, Carlson, CS, Newcomb, PA, Giovannucci, E, Hsu, L, Chan, AT, Peters, U & Chang-Claude, J 2016, 'CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk', British Journal of Cancer, vol. 114, no. 2, pp. 221-229. https://doi.org/10.1038/bjc.2015.443
Garcia-Albeniz, Xabier ; Rudolph, Anja ; Hutter, Carolyn ; White, Emily ; Lin, Yi ; Rosse, Stephanie A. ; Figueiredo, Jane C. ; Harrison, Tabitha A. ; Jiao, Shuo ; Brenner, Hermann ; Casey, Graham ; Hudson, Thomas J. ; Thornquist, Mark ; Le Marchand, Loic ; Potter, John ; Slattery, Martha L. ; Zanke, Brent ; Baron, John A. ; Caan, Bette J. ; Chanock, Stephen J. ; Berndt, Sonja I. ; Stelling, Deanna ; Fuchs, Charles S. ; Hoffmeister, Michael ; Butterbach, Katja ; Du, Mengmeng ; James Gauderman, W. ; Gunter, Marc J. ; Lemire, Mathieu ; Ogino, Shuji ; Lin, Jennifer ; Hayes, Richard B. ; Haile, Robert W. ; Schoen, Robert E. ; Warnick, Greg S. ; Jenkins, Mark A. ; Thibodeau, Stephen N ; Schumacher, Fredrick R. ; Lindor, Noralane Morey ; Kolonel, Laurence N. ; Hopper, John L. ; Gong, Jian ; Seminara, Daniela ; Pflugeisen, Bethann M. ; Ulrich, Cornelia M. ; Qu, Conghui ; Duggan, David ; Cotterchio, Michelle ; Campbell, Peter T. ; Carlson, Christopher S. ; Newcomb, Polly A. ; Giovannucci, Edward ; Hsu, Li ; Chan, Andrew T. ; Peters, Ulrike ; Chang-Claude, Jenny. / CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. In: British Journal of Cancer. 2016 ; Vol. 114, No. 2. pp. 221-229.
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title = "CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk",
abstract = "Background:Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods:We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test.Results:The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95{\%} CIs)=0.61 (0.52-0.72), P=4.8 × 10 -9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10 -5 (alpha threshold=3.1 × 10 -4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively.Conclusions:Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.",
author = "Xabier Garcia-Albeniz and Anja Rudolph and Carolyn Hutter and Emily White and Yi Lin and Rosse, {Stephanie A.} and Figueiredo, {Jane C.} and Harrison, {Tabitha A.} and Shuo Jiao and Hermann Brenner and Graham Casey and Hudson, {Thomas J.} and Mark Thornquist and {Le Marchand}, Loic and John Potter and Slattery, {Martha L.} and Brent Zanke and Baron, {John A.} and Caan, {Bette J.} and Chanock, {Stephen J.} and Berndt, {Sonja I.} and Deanna Stelling and Fuchs, {Charles S.} and Michael Hoffmeister and Katja Butterbach and Mengmeng Du and {James Gauderman}, W. and Gunter, {Marc J.} and Mathieu Lemire and Shuji Ogino and Jennifer Lin and Hayes, {Richard B.} and Haile, {Robert W.} and Schoen, {Robert E.} and Warnick, {Greg S.} and Jenkins, {Mark A.} and Thibodeau, {Stephen N} and Schumacher, {Fredrick R.} and Lindor, {Noralane Morey} and Kolonel, {Laurence N.} and Hopper, {John L.} and Jian Gong and Daniela Seminara and Pflugeisen, {Bethann M.} and Ulrich, {Cornelia M.} and Conghui Qu and David Duggan and Michelle Cotterchio and Campbell, {Peter T.} and Carlson, {Christopher S.} and Newcomb, {Polly A.} and Edward Giovannucci and Li Hsu and Chan, {Andrew T.} and Ulrike Peters and Jenny Chang-Claude",
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TY - JOUR

T1 - CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk

AU - Garcia-Albeniz, Xabier

AU - Rudolph, Anja

AU - Hutter, Carolyn

AU - White, Emily

AU - Lin, Yi

AU - Rosse, Stephanie A.

AU - Figueiredo, Jane C.

AU - Harrison, Tabitha A.

AU - Jiao, Shuo

AU - Brenner, Hermann

AU - Casey, Graham

AU - Hudson, Thomas J.

AU - Thornquist, Mark

AU - Le Marchand, Loic

AU - Potter, John

AU - Slattery, Martha L.

AU - Zanke, Brent

AU - Baron, John A.

AU - Caan, Bette J.

AU - Chanock, Stephen J.

AU - Berndt, Sonja I.

AU - Stelling, Deanna

AU - Fuchs, Charles S.

AU - Hoffmeister, Michael

AU - Butterbach, Katja

AU - Du, Mengmeng

AU - James Gauderman, W.

AU - Gunter, Marc J.

AU - Lemire, Mathieu

AU - Ogino, Shuji

AU - Lin, Jennifer

AU - Hayes, Richard B.

AU - Haile, Robert W.

AU - Schoen, Robert E.

AU - Warnick, Greg S.

AU - Jenkins, Mark A.

AU - Thibodeau, Stephen N

AU - Schumacher, Fredrick R.

AU - Lindor, Noralane Morey

AU - Kolonel, Laurence N.

AU - Hopper, John L.

AU - Gong, Jian

AU - Seminara, Daniela

AU - Pflugeisen, Bethann M.

AU - Ulrich, Cornelia M.

AU - Qu, Conghui

AU - Duggan, David

AU - Cotterchio, Michelle

AU - Campbell, Peter T.

AU - Carlson, Christopher S.

AU - Newcomb, Polly A.

AU - Giovannucci, Edward

AU - Hsu, Li

AU - Chan, Andrew T.

AU - Peters, Ulrike

AU - Chang-Claude, Jenny

PY - 2016/1/19

Y1 - 2016/1/19

N2 - Background:Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods:We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test.Results:The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10 -9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10 -5 (alpha threshold=3.1 × 10 -4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively.Conclusions:Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

AB - Background:Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods:We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test.Results:The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10 -9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10 -5 (alpha threshold=3.1 × 10 -4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively.Conclusions:Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

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