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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

About this Publication
Title
Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.
Pubmed ID
38561434 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Br J Cancer. 2024 Jun; Volume 130 (Issue 10): Pages 1687-1696
Authors
Tian Y, Lin Y, Qu C, Arndt V, Baurley JW, Berndt SI, Bien SA, Bishop DT, Brenner H, Buchanan DD, Budiarto A, Campbell PT, Carreras-Torres R, Casey G, Chan AT, Chen R, Chen X, Conti DV, Díez-Obrero V, Dimou N, ...show more Drew DA, Figueiredo JC, Gallinger S, Giles GG, Gruber SB, Gunter MJ, Harlid S, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl KM, Joshi AD, Keku TO, Kawaguchi E, Kim AE, Kundaje A, Larsson SC, Marchand LL, Lewinger JP, Li L, Moreno V, Morrison J, Murphy N, Nan H, Nassir R, Newcomb PA, Obón-Santacana M, Ogino S, Ose J, Pardamean B, Pellatt AJ, Peoples AR, Platz EA, Potter JD, Prentice RL, Rennert G, Ruiz-Narvaez EA, Sakoda LC, Schoen RE, Shcherbina A, Stern MC, Su YR, Thibodeau SN, Thomas DC, Tsilidis KK, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, White E, Wolk A, Woods MO, Wu AH, Peters U, Gauderman WJ, Hsu L, Chang-Claude J
Affiliations
  • School of Public Health, Capital Medical University, Beijing, China.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia.
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
...show more
  • Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
  • Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
  • Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
  • Department of Genetics, Stanford University, Stanford, CA, USA.
  • Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
  • University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
  • Department of Global Health, Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA.
  • Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.
  • Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
  • Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Biomedical Informatics Program, Department of Biomedical Data Sciences, Stanford University, Stanford, CA, USA.
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
  • Memorial University of Newfoundland, Discipline of Genetics, St. John's, NL, Canada.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. lih@fredhutch.org.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. j.chang-claude@dkfz.de.
Abstract

BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.

METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.

RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.

CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

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