CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk
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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 M; 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: BRIT J CANCER, Jahrgang 114, Nr. 2, 19.01.2016, S. 221-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 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.
U2 - 10.1038/bjc.2015.443
DO - 10.1038/bjc.2015.443
M3 - SCORING: Journal article
C2 - 26766742
VL - 114
SP - 221
EP - 229
JO - BRIT J CANCER
JF - BRIT J CANCER
SN - 0007-0920
IS - 2
ER -