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Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Kho, Pik-Fang 
Amant, Frederic 
Annibali, Daniela 
Ashton, Katie 
Attia, John 

Abstract

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Description

Keywords

HDL cholesterol, LDL cholesterol, Mendelian randomization, endometrial cancer risk, triglycerides, Case-Control Studies, Cholesterol, HDL, Cholesterol, LDL, Endometrial Neoplasms, Female, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Risk, Triglycerides

Journal Title

Int J Cancer

Conference Name

Journal ISSN

0020-7136
1097-0215

Volume Title

148

Publisher

Wiley

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (16565)
National Cancer Institute (U19CA148537)
European Commission (223175)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
National Health and Medical Research Council (1109286)
Cancer Research UK (A10710)
Cancer Research UK (A16563)
Cancer Research UK (A12014)
Cancer Research UK (A10118)
National Health and Medical Research Council (1031333)
National Institutes of Health (NIH) (via Mayo Clinic) (1R01CA128978-01A2)