Epidemiology

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

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.

Conclusion

For people with Lynch syndrome, self-reported type-2 diabetes mellitus and high cholesterol were associated with increased colorectal cancer risk.

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Acknowledgements

We thank all study participants of the CCFR and staff for their contributions to this project. The content of this paper does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating sites in the CCFR, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the CCFR.

Author contributions

S.G.D., W.Y.L., A.K.W.—study design and concept, acquisition of data, analysis and interpretation of the data, drafting of the paper, approval of the final version of the paper; M.C., C.R., I.M.W., F.A.M., G.G.G., S.H., X.H., S.N.T., J.C.F., G.C., R.W.H., S.G., L.L.M., P.A.N., J.D.P., N.M.L., J.L.H., M.A.J.—acquisition of data, interpretation of the data, critical revision of the paper, approval of the final version of the paper.

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Correspondence to Aung Ko Win.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Informed consent was obtained from all study participants and the study protocol was approved by the Human Research Ethics Committees from each recruitment site of the Colon Cancer Family Registry. The study was approved by the Colon Cancer Family Registry Steering Committee (ID C-AU-0208-01). The study was performed in accordance with the Declaration of Helsinki.

Funding

This work was supported by supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under Award Number U01 CA167551 and through NCI/NIH cooperative agreements with the following Colon Cancer Family Registry (CCFR) sites: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Mayo Colon Cancer Family Registry (U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783), Seattle Familial Colorectal Cancer Registry (U01/U24 CA074794), Hawaii Family Registry of Colon Cancer (U01/U24 CA074806 and R01 CA104132 to L LeMarchand), and Cedars-Sinai Medical Center Consortium (U01/U24 CA074799). Additional support for case ascertainment was provided from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute to Fred Hutchinson Cancer Research Center (Control Nos. N01-CN-67009 and N01-PC-35142, and Contract No. HHSN2612013000121), the Hawaii Department of Health (Control Nos. N01-PC-67001 and N01-PC-35137, and Contract No. HHSN26120100037C), and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California and HHSN261201000140C awarded to the Cancer Prevention Institute of California), the following U.S. state cancer registries: AZ, CO, MN, NC, NH, and by the Victorian Cancer Registry, Australia and the Ontario Cancer Registry, Canada. This study was also supported by the Australian National Health and Medical Research Council (NHMRC) Fellowships awarded to AKW, DDB (Career Development Fellowships), MAJ (Senior Research Fellowship) and JLH (Senior Principal Research Fellowship). DDB is also funded by a University of Melbourne Research at Melbourne Accelerator Program (R@MAP).

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Data availability

The data supporting the results reported in this article are available from the Colon Cancer Family Registry (https://www.coloncfr.org/). The data are not publicly available and are subject to data use agreement.

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Dashti, S.G., Li, W.Y., Buchanan, D.D. et al. Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome. Br J Cancer 121, 869–876 (2019). https://doi.org/10.1038/s41416-019-0580-9

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