CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.
Br J Cancer
; 114(2): 221-9, 2016 Jan 19.
Article
en En
| MEDLINE
| ID: mdl-26766742
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Progestinas
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Neoplasias Colorrectales
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Adenocarcinoma
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Terapia de Reemplazo de Estrógeno
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Estrógenos
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Vitamina D3 24-Hidroxilasa
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos