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. Chanock; Sonja 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 M. 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

doi:10.1038/bjc.2015.443

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 M. 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 journal › Article › peer-review

16 Scopus citations

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 language	English (US)
Pages (from-to)	221-229
Number of pages	9
Journal	British journal of cancer
Volume	114
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2015.443
State	Published - Jan 19 2016

ASJC Scopus subject areas

Oncology
Cancer Research

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Garcia-Albeniz, X., Rudolph, A., Hutter, C., White, E., Lin, Y., Rosse, S. A., Figueiredo, J. C., Harrison, T. A., Jiao, S., Brenner, H., Casey, G., Hudson, T. J., Thornquist, M., Le Marchand, L., Potter, J., Slattery, M. L., Zanke, B., Baron, J. A., Caan, B. J., ... 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

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

@article{6504b8e057f84d9799c8fc99468fd251,

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 M.} 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",

note = "Publisher Copyright: {\textcopyright} 2016 Cancer Research UK.",

year = "2016",

month = jan,

day = "19",

doi = "10.1038/bjc.2015.443",

language = "English (US)",

volume = "114",

pages = "221--229",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "2",

}

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 M.

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

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