| Literature DB >> 32851660 |
Pik-Fang Kho1,2, Frederic Amant3, Daniela Annibali3, Katie Ashton4,5,6, John Attia4,7, Paul L Auer8,9, Matthias W Beckmann10, Amanda Black11, Louise Brinton11, Daniel D Buchanan12,13,14,15, Stephen J Chanock16, Chu Chen17, Maxine M Chen18, Timothy H T Cheng19, Linda S Cook20,21, Marta Crous-Bous18,22, Kamila Czene23, Immaculata De Vivo18,22, Joe Dennis24, Thilo Dörk25, Sean C Dowdy26, Alison M Dunning27, Matthias Dürst28, Douglas F Easton24,27, Arif B Ekici29, Peter A Fasching10,30, Brooke L Fridley31, Christine M Friedenreich21, Montserrat García-Closas16, Mia M Gaudet32, Graham G Giles13,33,34, Ellen L Goode35, Maggie Gorman19, Christopher A Haiman36, Per Hall23,37, Susan E Hankinson22,38, Alexander Hein10, Peter Hillemanns25, Shirley Hodgson39, Erling A Hoivik40,41, Elizabeth G Holliday4,7, David J Hunter18,42,43, Angela Jones19, Peter Kraft18,42, Camilla Krakstad40,41, Diether Lambrechts44,45, Loic Le Marchand46, Xiaolin Liang47, Annika Lindblom48,49, Jolanta Lissowska50, Jirong Long51, Lingeng Lu52, Anthony M Magliocco53, Lynn Martin54, Mark McEvoy7, Roger L Milne13,33,34, Miriam Mints55, Rami Nassir56, Geoffrey Otton57, Claire Palles19, Loreall Pooler36, Tony Proietto57, Timothy R Rebbeck58,59, Stefan P Renner60, Harvey A Risch52, Matthias Rübner60, Ingo Runnebaum28, Carlotta Sacerdote61,62, Gloria E Sarto63, Fredrick Schumacher64, Rodney J Scott4,6,65, V Wendy Setiawan36, Mitul Shah27, Xin Sheng36, Xiao-Ou Shu51, Melissa C Southey12,33,34, Emma Tham48,66, Ian Tomlinson19,54, Jone Trovik40,41, Constance Turman18, Jonathan P Tyrer27, David Van Den Berg36, Zhaoming Wang11, Nicolas Wentzensen11, Lucy Xia36, Yong-Bing Xiang67, Hannah P Yang11, Herbert Yu46, Wei Zheng51, Penelope M Webb68, Deborah J Thompson24, Amanda B Spurdle1, Dylan M Glubb1, Tracy A O'Mara1.
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.Entities:
Keywords: HDL cholesterol; LDL cholesterol; Mendelian randomization; endometrial cancer risk; triglycerides
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Year: 2020 PMID： 32851660 PMCID： PMC7757859 DOI： 10.1002/ijc.33206
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.396