Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer
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 per...
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| Veröffentlicht in: | INTERNATIONAL JOURNAL OF CANCER 2021-01, Vol.148 (2), p.307-319 |
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| 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 Doerk, Thilo Dowdy, Sean C Dunning, Alison M Duerst, Matthias Easton, Douglas F Ekici, Arif B Fasching, Peter A Fridley, Brooke L Friedenreich, Christine M Garcia-Closas, Montserrat Gaudet, Mia M Giles, Graham G Goode, Ellen L Gorman, Maggie Haiman, Christopher A Hall, Per Hankinson, Susan E Hein, Alexander Hillemanns, Peter Hodgson, Shirley Hoivik, Erling A Holliday, Elizabeth G Hunter, David J Jones, Angela Kraft, Peter Krakstad, Camilla Lambrechts, Diether Le Marchand, Loic Liang, Xiaolin Lindblom, Annika Lissowska, Jolanta Long, Jirong Lu, Lingeng Magliocco, Anthony M Martin, Lynn McEvoy, Mark Milne, Roger L Mints, Miriam Nassir, Rami Otton, Geoffrey Palles, Claire Pooler, Loreall Proietto, Tony Rebbeck, Timothy R Renner, Stefan P Risch, Harvey A Ruebner, Matthias Runnebaum, Ingo Sacerdote, Carlotta Sarto, Gloria E Schumacher, Fredrick Scott, Rodney J Setiawan, V. Wendy Shah, Mitul Sheng, Xin Shu, Xiao-Ou Southey, Melissa C Tham, Emma Tomlinson, Ian Trovik, Jone Turman, Constance Tyrer, Jonathan P van den Berg, David Wang, Zhaoming Wentzensen, Nicolas Xia, Lucy Xiang, Yong-Bing Yang, Hannah P Yu, Herbert Zheng, Wei Webb, Penelope M Thompson, Deborah J Spurdle, Amanda B Glubb, Dylan M O'Mara, Tracy A |
| 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 |
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Wendy ; Shah, Mitul ; Sheng, Xin ; Shu, Xiao-Ou ; Southey, Melissa C ; Tham, Emma ; Tomlinson, Ian ; Trovik, Jone ; Turman, Constance ; Tyrer, Jonathan P ; van den Berg, David ; Wang, Zhaoming ; Wentzensen, Nicolas ; Xia, Lucy ; Xiang, Yong-Bing ; Yang, Hannah P ; Yu, Herbert ; Zheng, Wei ; Webb, Penelope M ; Thompson, Deborah J ; Spurdle, Amanda B ; Glubb, Dylan M ; O'Mara, Tracy A</creator><creatorcontrib>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 ; Doerk, Thilo ; Dowdy, Sean C ; Dunning, Alison M ; Duerst, Matthias ; Easton, Douglas F ; Ekici, Arif B ; Fasching, Peter A ; Fridley, Brooke L ; Friedenreich, Christine M ; Garcia-Closas, Montserrat ; Gaudet, Mia M ; Giles, Graham G ; Goode, Ellen L ; Gorman, Maggie ; Haiman, Christopher A ; Hall, Per ; Hankinson, Susan E ; Hein, Alexander ; Hillemanns, Peter ; Hodgson, Shirley ; Hoivik, Erling A ; Holliday, Elizabeth G ; Hunter, David J ; Jones, Angela ; Kraft, Peter ; Krakstad, Camilla ; Lambrechts, Diether ; Le Marchand, Loic ; Liang, Xiaolin ; Lindblom, Annika ; Lissowska, Jolanta ; Long, Jirong ; Lu, Lingeng ; Magliocco, Anthony M ; Martin, Lynn ; McEvoy, Mark ; Milne, Roger L ; Mints, Miriam ; Nassir, Rami ; Otton, Geoffrey ; Palles, Claire ; Pooler, Loreall ; Proietto, Tony ; Rebbeck, Timothy R ; Renner, Stefan P ; Risch, Harvey A ; Ruebner, Matthias ; Runnebaum, Ingo ; Sacerdote, Carlotta ; Sarto, Gloria E ; Schumacher, Fredrick ; Scott, Rodney J ; Setiawan, V. Wendy ; Shah, Mitul ; Sheng, Xin ; Shu, Xiao-Ou ; Southey, Melissa C ; Tham, Emma ; Tomlinson, Ian ; Trovik, Jone ; Turman, Constance ; Tyrer, Jonathan P ; van den Berg, David ; Wang, Zhaoming ; Wentzensen, Nicolas ; Xia, Lucy ; Xiang, Yong-Bing ; Yang, Hannah P ; Yu, Herbert ; Zheng, Wei ; Webb, Penelope M ; Thompson, Deborah J ; Spurdle, Amanda B ; Glubb, Dylan M ; O'Mara, Tracy A</creatorcontrib><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.</description><identifier>ISSN: 0020-7136</identifier><language>eng</language><publisher>WILEY</publisher><ispartof>INTERNATIONAL JOURNAL OF CANCER, 2021-01, Vol.148 (2), p.307-319</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27837</link.rule.ids></links><search><creatorcontrib>Kho, Pik-Fang</creatorcontrib><creatorcontrib>Amant, Frederic</creatorcontrib><creatorcontrib>Annibali, Daniela</creatorcontrib><creatorcontrib>Ashton, Katie</creatorcontrib><creatorcontrib>Attia, John</creatorcontrib><creatorcontrib>Auer, Paul L</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Black, Amanda</creatorcontrib><creatorcontrib>Brinton, Louise</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Chen, Maxine M</creatorcontrib><creatorcontrib>Cheng, Timothy H.T</creatorcontrib><creatorcontrib>Cook, Linda S</creatorcontrib><creatorcontrib>Crous-Bous, Marta</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>De Vivo, Immaculata</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Doerk, Thilo</creatorcontrib><creatorcontrib>Dowdy, Sean C</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Duerst, Matthias</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Ekici, Arif B</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Fridley, Brooke L</creatorcontrib><creatorcontrib>Friedenreich, Christine M</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><creatorcontrib>Gaudet, Mia M</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Goode, Ellen L</creatorcontrib><creatorcontrib>Gorman, Maggie</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Hankinson, Susan E</creatorcontrib><creatorcontrib>Hein, Alexander</creatorcontrib><creatorcontrib>Hillemanns, Peter</creatorcontrib><creatorcontrib>Hodgson, Shirley</creatorcontrib><creatorcontrib>Hoivik, Erling A</creatorcontrib><creatorcontrib>Holliday, Elizabeth G</creatorcontrib><creatorcontrib>Hunter, David J</creatorcontrib><creatorcontrib>Jones, Angela</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Krakstad, Camilla</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Liang, Xiaolin</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Long, Jirong</creatorcontrib><creatorcontrib>Lu, Lingeng</creatorcontrib><creatorcontrib>Magliocco, Anthony M</creatorcontrib><creatorcontrib>Martin, Lynn</creatorcontrib><creatorcontrib>McEvoy, Mark</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Mints, Miriam</creatorcontrib><creatorcontrib>Nassir, Rami</creatorcontrib><creatorcontrib>Otton, Geoffrey</creatorcontrib><creatorcontrib>Palles, Claire</creatorcontrib><creatorcontrib>Pooler, Loreall</creatorcontrib><creatorcontrib>Proietto, Tony</creatorcontrib><creatorcontrib>Rebbeck, Timothy R</creatorcontrib><creatorcontrib>Renner, Stefan P</creatorcontrib><creatorcontrib>Risch, Harvey A</creatorcontrib><creatorcontrib>Ruebner, Matthias</creatorcontrib><creatorcontrib>Runnebaum, Ingo</creatorcontrib><creatorcontrib>Sacerdote, Carlotta</creatorcontrib><creatorcontrib>Sarto, Gloria E</creatorcontrib><creatorcontrib>Schumacher, Fredrick</creatorcontrib><creatorcontrib>Scott, Rodney J</creatorcontrib><creatorcontrib>Setiawan, V. Wendy</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Sheng, Xin</creatorcontrib><creatorcontrib>Shu, Xiao-Ou</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><creatorcontrib>Tham, Emma</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Trovik, Jone</creatorcontrib><creatorcontrib>Turman, Constance</creatorcontrib><creatorcontrib>Tyrer, Jonathan P</creatorcontrib><creatorcontrib>van den Berg, David</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Wentzensen, Nicolas</creatorcontrib><creatorcontrib>Xia, Lucy</creatorcontrib><creatorcontrib>Xiang, Yong-Bing</creatorcontrib><creatorcontrib>Yang, Hannah P</creatorcontrib><creatorcontrib>Yu, Herbert</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><creatorcontrib>Webb, Penelope M</creatorcontrib><creatorcontrib>Thompson, Deborah J</creatorcontrib><creatorcontrib>Spurdle, Amanda B</creatorcontrib><creatorcontrib>Glubb, Dylan M</creatorcontrib><creatorcontrib>O'Mara, Tracy A</creatorcontrib><title>Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer</title><title>INTERNATIONAL JOURNAL OF CANCER</title><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.</description><issn>0020-7136</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqNjLtuwkAQRbcAiVf-YToKhLTGYEONEqWho7dG9jXesMyinTUK-fqAxAdQnaujqzMwY2tXdllmeTEyE9Ufa7NsY9dj0x0gDbxjocjShIv74-SCEAv7u0JJ-9MJmogpBg9qQ6S6eyxNeAhyQqkDNbjBh-sFkii0hGcKKTr2VLPUiDMzbNkrPl6cmvnX53H_vTz3Hv0NUjV65RpVtsrXm6Lc7qqiKO2uzKdm8d6zSr8pf7_7D-0bVtw</recordid><startdate>20210115</startdate><enddate>20210115</enddate><creator>Kho, Pik-Fang</creator><creator>Amant, Frederic</creator><creator>Annibali, Daniela</creator><creator>Ashton, Katie</creator><creator>Attia, John</creator><creator>Auer, Paul L</creator><creator>Beckmann, Matthias W</creator><creator>Black, Amanda</creator><creator>Brinton, Louise</creator><creator>Buchanan, Daniel D</creator><creator>Chanock, Stephen J</creator><creator>Chen, Chu</creator><creator>Chen, Maxine M</creator><creator>Cheng, Timothy H.T</creator><creator>Cook, Linda S</creator><creator>Crous-Bous, Marta</creator><creator>Czene, Kamila</creator><creator>De Vivo, Immaculata</creator><creator>Dennis, Joe</creator><creator>Doerk, Thilo</creator><creator>Dowdy, Sean C</creator><creator>Dunning, Alison M</creator><creator>Duerst, Matthias</creator><creator>Easton, Douglas F</creator><creator>Ekici, Arif B</creator><creator>Fasching, Peter A</creator><creator>Fridley, Brooke L</creator><creator>Friedenreich, Christine M</creator><creator>Garcia-Closas, Montserrat</creator><creator>Gaudet, Mia M</creator><creator>Giles, Graham G</creator><creator>Goode, Ellen L</creator><creator>Gorman, Maggie</creator><creator>Haiman, Christopher A</creator><creator>Hall, Per</creator><creator>Hankinson, Susan E</creator><creator>Hein, Alexander</creator><creator>Hillemanns, Peter</creator><creator>Hodgson, Shirley</creator><creator>Hoivik, Erling A</creator><creator>Holliday, Elizabeth G</creator><creator>Hunter, David J</creator><creator>Jones, Angela</creator><creator>Kraft, Peter</creator><creator>Krakstad, Camilla</creator><creator>Lambrechts, Diether</creator><creator>Le Marchand, Loic</creator><creator>Liang, Xiaolin</creator><creator>Lindblom, Annika</creator><creator>Lissowska, Jolanta</creator><creator>Long, Jirong</creator><creator>Lu, Lingeng</creator><creator>Magliocco, Anthony M</creator><creator>Martin, Lynn</creator><creator>McEvoy, Mark</creator><creator>Milne, Roger L</creator><creator>Mints, Miriam</creator><creator>Nassir, Rami</creator><creator>Otton, Geoffrey</creator><creator>Palles, Claire</creator><creator>Pooler, Loreall</creator><creator>Proietto, Tony</creator><creator>Rebbeck, Timothy R</creator><creator>Renner, Stefan P</creator><creator>Risch, Harvey A</creator><creator>Ruebner, Matthias</creator><creator>Runnebaum, Ingo</creator><creator>Sacerdote, Carlotta</creator><creator>Sarto, Gloria E</creator><creator>Schumacher, Fredrick</creator><creator>Scott, Rodney J</creator><creator>Setiawan, V. 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Wendy ; Shah, Mitul ; Sheng, Xin ; Shu, Xiao-Ou ; Southey, Melissa C ; Tham, Emma ; Tomlinson, Ian ; Trovik, Jone ; Turman, Constance ; Tyrer, Jonathan P ; van den Berg, David ; Wang, Zhaoming ; Wentzensen, Nicolas ; Xia, Lucy ; Xiang, Yong-Bing ; Yang, Hannah P ; Yu, Herbert ; Zheng, Wei ; Webb, Penelope M ; Thompson, Deborah J ; Spurdle, Amanda B ; Glubb, Dylan M ; O'Mara, Tracy A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-kuleuven_dspace_123456789_6670973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kho, Pik-Fang</creatorcontrib><creatorcontrib>Amant, Frederic</creatorcontrib><creatorcontrib>Annibali, Daniela</creatorcontrib><creatorcontrib>Ashton, Katie</creatorcontrib><creatorcontrib>Attia, John</creatorcontrib><creatorcontrib>Auer, Paul L</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Black, Amanda</creatorcontrib><creatorcontrib>Brinton, Louise</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Chen, Maxine M</creatorcontrib><creatorcontrib>Cheng, Timothy H.T</creatorcontrib><creatorcontrib>Cook, Linda S</creatorcontrib><creatorcontrib>Crous-Bous, Marta</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>De Vivo, Immaculata</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Doerk, Thilo</creatorcontrib><creatorcontrib>Dowdy, Sean C</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Duerst, Matthias</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Ekici, Arif B</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Fridley, Brooke L</creatorcontrib><creatorcontrib>Friedenreich, Christine M</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><creatorcontrib>Gaudet, Mia M</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Goode, Ellen L</creatorcontrib><creatorcontrib>Gorman, Maggie</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Hankinson, Susan E</creatorcontrib><creatorcontrib>Hein, Alexander</creatorcontrib><creatorcontrib>Hillemanns, Peter</creatorcontrib><creatorcontrib>Hodgson, Shirley</creatorcontrib><creatorcontrib>Hoivik, Erling A</creatorcontrib><creatorcontrib>Holliday, Elizabeth G</creatorcontrib><creatorcontrib>Hunter, David J</creatorcontrib><creatorcontrib>Jones, Angela</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Krakstad, Camilla</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Liang, Xiaolin</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Long, Jirong</creatorcontrib><creatorcontrib>Lu, Lingeng</creatorcontrib><creatorcontrib>Magliocco, Anthony M</creatorcontrib><creatorcontrib>Martin, Lynn</creatorcontrib><creatorcontrib>McEvoy, Mark</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Mints, Miriam</creatorcontrib><creatorcontrib>Nassir, Rami</creatorcontrib><creatorcontrib>Otton, Geoffrey</creatorcontrib><creatorcontrib>Palles, Claire</creatorcontrib><creatorcontrib>Pooler, Loreall</creatorcontrib><creatorcontrib>Proietto, Tony</creatorcontrib><creatorcontrib>Rebbeck, Timothy R</creatorcontrib><creatorcontrib>Renner, Stefan P</creatorcontrib><creatorcontrib>Risch, Harvey A</creatorcontrib><creatorcontrib>Ruebner, Matthias</creatorcontrib><creatorcontrib>Runnebaum, Ingo</creatorcontrib><creatorcontrib>Sacerdote, Carlotta</creatorcontrib><creatorcontrib>Sarto, Gloria E</creatorcontrib><creatorcontrib>Schumacher, Fredrick</creatorcontrib><creatorcontrib>Scott, Rodney J</creatorcontrib><creatorcontrib>Setiawan, V. Wendy</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Sheng, Xin</creatorcontrib><creatorcontrib>Shu, Xiao-Ou</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><creatorcontrib>Tham, Emma</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Trovik, Jone</creatorcontrib><creatorcontrib>Turman, Constance</creatorcontrib><creatorcontrib>Tyrer, Jonathan P</creatorcontrib><creatorcontrib>van den Berg, David</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Wentzensen, Nicolas</creatorcontrib><creatorcontrib>Xia, Lucy</creatorcontrib><creatorcontrib>Xiang, Yong-Bing</creatorcontrib><creatorcontrib>Yang, Hannah P</creatorcontrib><creatorcontrib>Yu, Herbert</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><creatorcontrib>Webb, Penelope M</creatorcontrib><creatorcontrib>Thompson, Deborah J</creatorcontrib><creatorcontrib>Spurdle, Amanda B</creatorcontrib><creatorcontrib>Glubb, Dylan M</creatorcontrib><creatorcontrib>O'Mara, Tracy A</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>INTERNATIONAL JOURNAL OF CANCER</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kho, Pik-Fang</au><au>Amant, Frederic</au><au>Annibali, Daniela</au><au>Ashton, Katie</au><au>Attia, John</au><au>Auer, Paul L</au><au>Beckmann, Matthias W</au><au>Black, Amanda</au><au>Brinton, Louise</au><au>Buchanan, Daniel D</au><au>Chanock, Stephen J</au><au>Chen, Chu</au><au>Chen, Maxine M</au><au>Cheng, Timothy H.T</au><au>Cook, Linda S</au><au>Crous-Bous, Marta</au><au>Czene, Kamila</au><au>De Vivo, Immaculata</au><au>Dennis, Joe</au><au>Doerk, Thilo</au><au>Dowdy, Sean C</au><au>Dunning, Alison M</au><au>Duerst, Matthias</au><au>Easton, Douglas F</au><au>Ekici, Arif B</au><au>Fasching, Peter A</au><au>Fridley, Brooke L</au><au>Friedenreich, Christine M</au><au>Garcia-Closas, Montserrat</au><au>Gaudet, Mia M</au><au>Giles, Graham G</au><au>Goode, Ellen L</au><au>Gorman, Maggie</au><au>Haiman, Christopher A</au><au>Hall, Per</au><au>Hankinson, Susan E</au><au>Hein, Alexander</au><au>Hillemanns, Peter</au><au>Hodgson, Shirley</au><au>Hoivik, Erling A</au><au>Holliday, Elizabeth G</au><au>Hunter, David J</au><au>Jones, Angela</au><au>Kraft, Peter</au><au>Krakstad, Camilla</au><au>Lambrechts, Diether</au><au>Le Marchand, Loic</au><au>Liang, Xiaolin</au><au>Lindblom, Annika</au><au>Lissowska, Jolanta</au><au>Long, Jirong</au><au>Lu, Lingeng</au><au>Magliocco, Anthony M</au><au>Martin, Lynn</au><au>McEvoy, Mark</au><au>Milne, Roger L</au><au>Mints, Miriam</au><au>Nassir, Rami</au><au>Otton, Geoffrey</au><au>Palles, Claire</au><au>Pooler, Loreall</au><au>Proietto, Tony</au><au>Rebbeck, Timothy R</au><au>Renner, Stefan P</au><au>Risch, Harvey A</au><au>Ruebner, Matthias</au><au>Runnebaum, Ingo</au><au>Sacerdote, Carlotta</au><au>Sarto, Gloria E</au><au>Schumacher, Fredrick</au><au>Scott, Rodney J</au><au>Setiawan, V. Wendy</au><au>Shah, Mitul</au><au>Sheng, Xin</au><au>Shu, Xiao-Ou</au><au>Southey, Melissa C</au><au>Tham, Emma</au><au>Tomlinson, Ian</au><au>Trovik, Jone</au><au>Turman, Constance</au><au>Tyrer, Jonathan P</au><au>van den Berg, David</au><au>Wang, Zhaoming</au><au>Wentzensen, Nicolas</au><au>Xia, Lucy</au><au>Xiang, Yong-Bing</au><au>Yang, Hannah P</au><au>Yu, Herbert</au><au>Zheng, Wei</au><au>Webb, Penelope M</au><au>Thompson, Deborah J</au><au>Spurdle, Amanda B</au><au>Glubb, Dylan M</au><au>O'Mara, Tracy A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer</atitle><jtitle>INTERNATIONAL JOURNAL OF CANCER</jtitle><date>2021-01-15</date><risdate>2021</risdate><volume>148</volume><issue>2</issue><spage>307</spage><epage>319</epage><pages>307-319</pages><issn>0020-7136</issn><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.</abstract><pub>WILEY</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | INTERNATIONAL JOURNAL OF CANCER, 2021-01, Vol.148 (2), p.307-319 |
| issn | 0020-7136 |
| language | eng |
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| source | Lirias (KU Leuven Association); Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| title | Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer |
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