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Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome.
J Natl Cancer Inst 2015; 107(9)JNCI

Abstract

BACKGROUND

Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers.

METHODS

We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.

RESULTS

A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use.

CONCLUSION

Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer.

Authors+Show Affiliations

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health ScienceCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia (DAO, SGD, RC, DDB, GGG, JLH, MAJ, AKW); Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (DDB, MC, CR); University of Queensland, School of Medicine, Herston, Queensland, Australia (CR); Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (IMW, FAM); Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia (IMW, FAM); Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia (JPY); SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia (JPY); School of Medicine, University of Adelaide, South Australia, Australia (JPY); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia (GGG); QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia (BL); Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia (FAM); Department of Medicine, University of Colorado School of Medicine, Denver, CO (DJA); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GC); Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (SG); Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, CA (RWH); University of Hawaii Cancer Center, Honolulu, HI (LLM); Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (SNT); Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Public Health Science

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26109217

Citation

Ait Ouakrim, Driss, et al. "Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome." Journal of the National Cancer Institute, vol. 107, no. 9, 2015.
Ait Ouakrim D, Dashti SG, Chau R, et al. Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. J Natl Cancer Inst. 2015;107(9).
Ait Ouakrim, D., Dashti, S. G., Chau, R., Buchanan, D. D., Clendenning, M., Rosty, C., ... Win, A. K. (2015). Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. Journal of the National Cancer Institute, 107(9), doi:10.1093/jnci/djv170.
Ait Ouakrim D, et al. Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. J Natl Cancer Inst. 2015;107(9) PubMed PMID: 26109217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. AU - Ait Ouakrim,Driss, AU - Dashti,Seyedeh Ghazaleh, AU - Chau,Rowena, AU - Buchanan,Daniel D, AU - Clendenning,Mark, AU - Rosty,Christophe, AU - Winship,Ingrid M, AU - Young,Joanne P, AU - Giles,Graham G, AU - Leggett,Barbara, AU - Macrae,Finlay A, AU - Ahnen,Dennis J, AU - Casey,Graham, AU - Gallinger,Steven, AU - Haile,Robert W, AU - Le Marchand,Loïc, AU - Thibodeau,Stephen N, AU - Lindor,Noralane M, AU - Newcomb,Polly A, AU - Potter,John D, AU - Baron,John A, AU - Hopper,John L, AU - Jenkins,Mark A, AU - Win,Aung Ko, Y1 - 2015/06/24/ PY - 2014/08/27/received PY - 2015/05/22/accepted PY - 2015/6/26/entrez PY - 2015/6/26/pubmed PY - 2015/10/13/medline JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 107 IS - 9 N2 - BACKGROUND: Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers. METHODS: We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use. CONCLUSION: Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/26109217/Aspirin_Ibuprofen_and_the_Risk_of_Colorectal_Cancer_in_Lynch_Syndrome_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djv170 DB - PRIME DP - Unbound Medicine ER -