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

About this Publication
Title
CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.
Pubmed ID
26766742 (View this publication on the PubMed website)
Publication
Br. J. Cancer. 2016 Jan; Volume 114 (Issue 2): Pages 221-9
Authors
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, ...show more 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
Affiliations
  • Department of Epidemiology, Harvard T.H., Chan School of Public Health, Boston, MA 02115, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
  • Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
  • Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada.
...show more
  • Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7080, USA.
  • Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94612, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4608, USA.
  • Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
  • Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY 10016, USA.
  • Department of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA.
  • Melbourne School of Population Health, The University of Melbourne, Melbourne, VIC 3010, Australia.
  • Departments of Laboratory Medicine, Pathology and Laboratory Genetics, Mayo Clinic, Scottsdale, AZ 85259, USA.
  • Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ 85259, USA.
  • Department of Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
  • Translational Genomics Research Institute (Tgen), Phoenix, AZ 85004, USA.
  • Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON M5G 2L7, Canada.
  • Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.
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.

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