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

• Verfasst von: Garcia-Albeniz, Xabier [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Hoffmeister, Michael [VerfasserIn]
• Verfasst von: Ulrich, Cornelia [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Titel: CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk
• Verf.angabe: 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 and Jenny Chang-Claude
• E-Jahr: 2016
• Jahr: 14 January 2016
• Umfang: 9 S.
• Teil: volume:114
• Teil: year:2016
• Teil: number:2
• Teil: pages:221-229
• Teil: extent:9
• Fussnoten: Gesehen am 13.05.2020
• Titel Quelle: Enthalten in: British journal of cancer
• Ort Quelle: Edinburgh : Nature Publ. Group, 1999
• Jahr Quelle: 2016
• Band/Heft Quelle: 114(2016), 2, Seite 221-229
• ISSN Quelle: 1532-1827
• DOI: doi:10.1038/bjc.2015.443
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adenocarcinoma
• Sach-SW: Aged
• Sach-SW: Bayes Theorem
• Sach-SW: Case-Control Studies
• Sach-SW: Colorectal Neoplasms
• Sach-SW: Drug Therapy, Combination
• Sach-SW: Estrogen Replacement Therapy
• Sach-SW: Estrogens
• Sach-SW: Female
• Sach-SW: Gene-Environment Interaction
• Sach-SW: Genetic Predisposition to Disease
• Sach-SW: Genome-Wide Association Study
• Sach-SW: Genotype
• Sach-SW: Humans
• Sach-SW: Logistic Models
• Sach-SW: Middle Aged
• Sach-SW: Polymorphism, Single Nucleotide
• Sach-SW: Progestins
• Sach-SW: Risk Factors
• Sach-SW: Vitamin D3 24-Hydroxylase
• K10plus-PPN: 1698107374

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.