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Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

About this Publication
Title
Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.
Pubmed ID
32923935 (View this publication on the PubMed website)
Digital Object Identifier
Publication
JNCI Cancer Spectr. 2020 Aug; Volume 4 (Issue 5): Pages pkaa042
Authors
Labadie JD, Harrison TA, Banbury B, Amtay EL, Bernd S, Brenner H, Buchanan DD, Campbell PT, Cao Y, Chan AT, Chang-Claude J, English D, Figueiredo JC, Gallinger SJ, Giles GG, Gunter MJ, Hoffmeister M, Hsu L, Jenkins MA, Lin Y, ...show more Milne RL, Moreno V, Murphy N, Ogino S, Phipps AI, Sakoda LC, Slattery ML, Southey MC, Sun W, Thibodeau SN, Van Guelpen B, Zaidi SH, Peters U, Newcomb PA
Affiliations
  • 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.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
  • Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
  • Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
  • Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, USA.
...show more
  • Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
  • Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
  • Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
  • Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Abstract

BACKGROUND: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location.

METHODS: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided.

RESULTS: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors.

CONCLUSIONS: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

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