Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 148, Issue 2, Pages 307-319Publisher
WILEY
DOI: 10.1002/ijc.33206
Keywords
endometrial cancer risk; HDL cholesterol; LDL cholesterol; Mendelian randomization; triglycerides
Categories
Funding
- Australian National Health and Medical Research Council
- Cancer Council Victoria
- Fred Hutchinson Cancer Research Center
- Susan G. Komen Breast Cancer Foundation
- Agency for Science, Technology and Research of Singapore (A*STAR)
- Swedish Cancer Society [11 0439]
- Swedish Labor Market Insurance [100069]
- Stockholm County Council [DF 07015, 20110141, 20110483, 20110222]
- Karolinska Institutet [DF 07015, 20110141, 20110483, 20110222]
- Haukeland University Hospital
- Research Council of Norway
- Norwegian Cancer Society
- Melzer Foundation
- Helse Vest Grant
- Mayo Foundation
- Fred C and Katherine B Andersen Foundation
- National Cancer Institute of United States Public Health Service [P50 CA136393, P30 CA15083, R01 CA122443]
- Verelst Foundation
- Rudolf Bartling Foundation
- ELAN fund of the University of Erlangen
- Cancer Council Tasmania [457636, 403031]
- Cancer Council Queensland [4196615]
- National Cancer Institute [U19 CA148065-01]
- US Department of Health and Human Services [HHSN271201100004C, HHSN268201100004C, HHSN268201100003C, HHSN268201100002C, HHSN268201100001C, HHSN268201100046C]
- National Heart, Lung, and Blood Institute
- Wellcome Trust Case Control Consortium (WTCCC) [090532/Z/09Z, 085475, 068545/Z/02]
- NHMRC Senior Research Fellowship [APP1061779]
- NHMRC Early Career Fellowship [APP1111246]
- Australian Government Research Training Program PhD Scholarship [1074383, 396414, 209057]
- QIMR Berghofer Postgraduate Top-Up Scholarship [1074383, 396414, 209057]
- Cancer UK Grant [C1287/A16563]
- Genome Canada [GPH-129344]
- US National Institutes of Health [R01-CA058598, R01-CA149429, U19-CA148112, CA1X01HG007491-01]
- Ovarian Cancer Research Fund
- Breast Cancer Research Foundation
- Canadian Institutes of Health Research (CIHR) [MOP-86727]
- US Department of Defence [W81XWH-10-1-0341]
- National Institutes of Health [CA128978]
- Cancer Research UK [C490/A10124, C8197/A16565, C5047/A10692, C5047/A15007, C5047/A8384, C1281/A12014, C12292/A11174, C1287/A10710, C1287/A10118]
- European Community's Seventh Framework Programme [223175]
- National Health and Medical Research Council (NHMRC) [339435, G0000934, 1031333, 552402, 1109286]
- NIH [R01 CA77398, R01 CA91019, 2R01 CA082838, CA128008, CA54281, KO5 CA92002, R35 CA39779, NO1 HD23166, RO3 CA80636, RO1 CA75977, RO1 CA 87538, RO1 CA105212, 1R01 CA134958, R01 CA49449, P01 CA087969, UM1 CA186107, U19 CA148065]
- VicHealth
- Post-Cancer GWAS initiative [1U19 CA148112, 1U19 CA148065, 1U19 CA148537]
- National Health and Medical Research Council of Australia [1109286] Funding Source: NHMRC
Ask authors/readers for more resources
This study used Mendelian randomization analysis to investigate the relationship between blood lipids and endometrial cancer risk. Genetically elevated LDL cholesterol levels were associated with reduced risk of endometrial cancer, while higher predicted HDL cholesterol levels were linked to increased risk of non-endometrioid endometrial cancer. Obesity may influence these associations, but triglycerides showed no evidence of involvement in endometrial cancer development.
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 x 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.
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