- Title
- Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer
- Creator
- Kho, Pik-Fang; Amant, Frederic; Annibali, Daniela; Ashton, Katie; Attia, John; Auer, Paul L.; Beckmann, Matthias W.; Black, Amanda; Brinton, Louise; Buchanan, Daniel D.; Chanock, Stephen J.; Chen, Chu; Chen, Maxine M.; Cheng, Timothy H. T.; Cook, Linda S.; Crous-Bous, Marta; Czene, Kamila; De Vivo, Immaculata; Dennis, Joe; Döerk, Thilo; Holliday, Elizabeth G.; McEvoy, Mark; Otton, Geoffrey; Proietto, Tony; Scott, Rodney J.; Dowdy, Sean C.; Dunning, AM; Duerst, M; Easton, DF; Ekici, AB; Fasching, PA; Fridley, BL; Friedenreich, CM; Garcia-Closas, M; Gaudet, MM; Giles, GG; Goode, EL; Gorman, M; Haiman, CA; Hall, P; Hankinson, SE; Hein, A; Hillemanns, P; Hodgson, S; Hoivik, EA; Hunter, DJ; Jones, A; Kraft, P; Krakstad, C; Lambrechts, D; Le Marchand, L; Liang, X; Lindblom, A; Lissowska, J; Long, J; Lu, L; Magliocco, AM; Martin, L; Milne, RL; Mints, M; Nassir, R; Palles, C; Pooler, L; Rebbeck, TR; Renner, SP; Risch, HA; Ruebner, M; Runnebaum, I; Sacerdote, C; Sarto, GE; Schumacher, F; Setiawan, VW; Shah, M; Sheng, X; Shu, X-O; Southey, MC; Tham, E; Tomlinson, I; Trovik, J; Turman, C; Tyrer, JP; van den Berg, D; Wang, Z; Wentzensen, N; Xia, L; Xiang, Y-B; Yang, HP; Yu, H; Zheng, W; Webb, PM; Thompson, DJ; Spurdle, AB; Glubb, DM; O'Mara, TA
- Relation
- NHMRC.APP1061779 http://purl.org/au-research/grants/nhmrc/1061779
- Relation
- International journal of Cancer Vol. 148, Issue 2, p. 307-319
- Publisher Link
- http://dx.doi.org/10.1002/ijc.33206
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- endometrial cancer risk; DHL cholesterol; LDL cholesterol; Mendelian randmization; triglycerides; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1462432
- Identifier
- uon:46467
- Identifier
- ISSN:0020-7136
- Rights
- This is the peer reviewed version of the following article: Kho, Pik-Fang; Amant, Frederic; Annibali, Daniela; Ashton, Katie; Attia, John; … [et al]. “Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer”. International journal of Cancer Vol. 148, Issue 2, p. 307-319 (2020), which has been published in final form at http://dx.doi.org/10.1002/ijc.33206. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
- Language
- eng
- Full Text
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