Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome.

Dashti SG1,2,3, Li WY1,2, Buchanan DD1,2,4,5, Clendenning M2,5, Rosty C2,5,6,7, Winship IM4,8, Macrae FA4,8,9, Giles GG1,3, Hardikar S10,11,12, Hua X12,13, Thibodeau SN14, Figueiredo JC15,16, Casey G17, Haile RW15, Gallinger S18, Le Marchand L19, Newcomb PA12,13, Potter JD12,13,20, Lindor NM21, Hopper JL1,2, Jenkins MA1,2, Win AK22,23,24.

Author information

1: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
2: Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC, 3000, Australia.
3: Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
4: Genetic Medicine, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
5: Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia.
6: Envoi Specialist Pathologists, Brisbane, QLD, 4059, Australia.
7: Faculty of Medicine, University of Queensland, Brisbane, QLD, 4006, Australia.
8: Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia.
9: Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
10: Department of Population Health Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
11: Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, 84112, USA.
12: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
13: School of Public Health, University of Washington, Seattle, WA, 98195, USA.
14: Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55455, USA.
15: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
16: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, USA.
17: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
18: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, M5G 1×5, Canada.
19: University of Hawaii Cancer Center, Honolulu, Hawaii, 96813, USA.
20: Centre for Public Health Research, Massey University, Wellington, 6140, New Zealand.
21: Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
22: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia. awin@unimelb.edu.au.
23: Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC, 3000, Australia. awin@unimelb.edu.au.
24: Genetic Medicine, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia. awin@unimelb.edu.au.

Abstract

BACKGROUND:

Type 2 diabetes mellitus and high total cholesterol and triglycerides are known to be associated with increased colorectal cancer risk for the general population. These associations are unknown for people with a germline DNA mismatch repair gene mutation (Lynch syndrome), who are at high risk of colorectal cancer.

METHODS:

This study included 2023 (56.4% female) carriers with a mismatch repair gene mutation (737 in MLH1, 928 in MSH2, 230 in MSH6, 106 in PMS2, 22 in EPCAM) recruited by the Colon Cancer Family Registry between 1998 and 2012. Weighted Cox regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between self-reported type 2 diabetes, high cholesterol, triglyceride and colorectal cancer risk.

RESULTS:

Overall, 802 carriers were diagnosed with colorectal cancer at a median age of 42 years. A higher risk of colorectal cancer was observed in those with self-reported type-2 diabetes (HR 1.92; 95% CI, 1.03-3.58) and high cholesterol (HR 1.76; CI 1.23-2.52) compared with those without these conditions. There was no evidence of high triglyceride being associated with colorectal cancer risk.