Efrat L Amitay1, Prudence R Carr1, Lina Jansen1, Viola Walter1, Wilfried Roth2,3, Esther Herpel3,4, Matthias Kloor5, Hendrik Bläker1,6,7, Jenny Chang-Claude8, Hermann Brenner9, Michael Hoffmeister1. 1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. 2. Institute of Pathology, University Medical Center Mainz, Mainz, Germany. 3. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. 4. NCT Tissue Bank, National Center for Tumor Diseases, Heidelberg, Germany. 5. Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. 6. Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany. 7. German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany. 8. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. 9. Institute of Pathology, Charité University Medicine, Berlin, Germany.
Abstract
BACKGROUND: Regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for a longer period has been inversely associated with colorectal cancer (CRC) risk. However, CRC is a heterogenic disease, and little is known regarding the associations with molecular pathological subtypes. METHODS: Analyses included 2444 cases with a first diagnosis of CRC and 3130 healthy controls from a German population-based case control study. Tumor tissue samples were analyzed for major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype, B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. Information on past and current use of NSAIDs, including aspirin, was obtained by standardized interviews. Multinomial logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Regular use of NSAIDs was associated with a reduced CRC risk if tumors were MSS (OR = 0.66, 95% CI = 0.57 to 0.77), BRAF wildtype (OR = 0.67, 95% CI = 0.58 to 0.78), or KRAS wildtype (OR = 0.68, 95% CI = 0.58 to 0.80). Regular NSAID use was less clearly and mostly not statistically significantly associated with CRC risk reduction for MSI-high, BRAF-mutated, or KRAS-mutated CRC. In more specific analyses on MSI-high CRC, regular use of NSAIDs was associated with much stronger risk reduction in the absence of BRAF or KRAS mutations (OR = 0.34, 95% CI = 0.18 to 0.65) but not with KRAS- or BRAF-mutated MSI-high CRC (Pheterogeneity < .001). Results for just aspirin use were similar. CONCLUSION: Our study suggests variation in risk reduction of CRC subtypes following regular use of NSAIDs and aspirin. Regular use of NSAIDs and aspirin may be more strongly associated with risk reduction of MSI-high CRC without KRAS or BRAF mutation.
BACKGROUND: Regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for a longer period has been inversely associated with colorectal cancer (CRC) risk. However, CRC is a heterogenic disease, and little is known regarding the associations with molecular pathological subtypes. METHODS: Analyses included 2444 cases with a first diagnosis of CRC and 3130 healthy controls from a German population-based case control study. Tumor tissue samples were analyzed for major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype, B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten ratsarcoma viral oncogene homolog gene (KRAS) mutation. Information on past and current use of NSAIDs, including aspirin, was obtained by standardized interviews. Multinomial logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Regular use of NSAIDs was associated with a reduced CRC risk if tumors were MSS (OR = 0.66, 95% CI = 0.57 to 0.77), BRAF wildtype (OR = 0.67, 95% CI = 0.58 to 0.78), or KRAS wildtype (OR = 0.68, 95% CI = 0.58 to 0.80). Regular NSAID use was less clearly and mostly not statistically significantly associated with CRC risk reduction for MSI-high, BRAF-mutated, or KRAS-mutated CRC. In more specific analyses on MSI-high CRC, regular use of NSAIDs was associated with much stronger risk reduction in the absence of BRAF or KRAS mutations (OR = 0.34, 95% CI = 0.18 to 0.65) but not with KRAS- or BRAF-mutated MSI-high CRC (Pheterogeneity < .001). Results for just aspirin use were similar. CONCLUSION: Our study suggests variation in risk reduction of CRC subtypes following regular use of NSAIDs and aspirin. Regular use of NSAIDs and aspirin may be more strongly associated with risk reduction of MSI-high CRC without KRAS or BRAF mutation.
Authors: Amelie Echle; Heike Irmgard Grabsch; Philip Quirke; Piet A van den Brandt; Nicholas P West; Gordon G A Hutchins; Lara R Heij; Xiuxiang Tan; Susan D Richman; Jeremias Krause; Elizabeth Alwers; Josien Jenniskens; Kelly Offermans; Richard Gray; Hermann Brenner; Jenny Chang-Claude; Christian Trautwein; Alexander T Pearson; Peter Boor; Tom Luedde; Nadine Therese Gaisa; Michael Hoffmeister; Jakob Nikolas Kather Journal: Gastroenterology Date: 2020-06-17 Impact factor: 22.682
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Authors: Julia D Labadie; Tabitha A Harrison; Barbara Banbury; Efrat L Amtay; Sonja Bernd; Hermann Brenner; Daniel D Buchanan; Peter T Campbell; Yin Cao; Andrew T Chan; Jenny Chang-Claude; Dallas English; Jane C Figueiredo; Steven J Gallinger; Graham G Giles; Marc J Gunter; Michael Hoffmeister; Li Hsu; Mark A Jenkins; Yi Lin; Roger L Milne; Victor Moreno; Neil Murphy; Shuji Ogino; Amanda I Phipps; Lori C Sakoda; Martha L Slattery; Melissa C Southey; Wei Sun; Stephen N Thibodeau; Bethany Van Guelpen; Syed H Zaidi; Ulrike Peters; Polly A Newcomb Journal: JNCI Cancer Spectr Date: 2020-05-19