Literature DB >> 27550749

Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer.

Jodie N Painter1, Tracy A O'Mara1, Louise Marquart1, Penelope M Webb, John Attia2,3, Sarah E Medland1, Timothy Cheng4, Joe Dennis5, Elizabeth G Holliday2,3, Mark McEvoy3, Rodney J Scott2,6,7,8, Shahana Ahmed9, Catherine S Healey9, Mitul Shah9, Maggie Gorman4, Lynn Martin4, Shirley V Hodgson10, Matthias W Beckmann11, Arif B Ekici12, Peter A Fasching11,13, Alexander Hein11, Matthias Rübner11, Kamila Czene14, Hatef Darabi14, Per Hall14, Jingmei Li14, Thilo Dörk15, Matthias Dürst16, Peter Hillemanns17, Ingo B Runnebaum16, Frederic Amant18, Daniela Annibali18, Jeroen Depreeuw18,19,20, Diether Lambrechts19,20, Patrick Neven18, Julie M Cunningham21, Sean C Dowdy22, Ellen L Goode23, Brooke L Fridley24, Stacey J Winham23, Tormund S Njølstad25,26, Helga B Salvesen25,26, Jone Trovik25,26, Henrica M J Werner25,26, Katie A Ashton2,7,8, Geoffrey Otton27, Anthony Proietto27, Miriam Mints28, Emma Tham, Manjeet K Bolla5, Kyriaki Michailidou5, Qin Wang5, Jonathan P Tyrer9, John L Hopper29, Julian Peto30, Anthony J Swerdlow31,32, Barbara Burwinkel33,34, Hermann Brenner35,36,37, Alfons Meindl38, Hiltrud Brauch37,39,40, Annika Lindblom41, Jenny Chang-Claude42,43, Fergus J Couch21,23, Graham G Giles29,44,45, Vessela N Kristensen46,47,48, Angela Cox49, Paul D P Pharoah9, Ian Tomlinson4, Alison M Dunning9, Douglas F Easton5,9, Deborah J Thompson, Amanda B Spurdle.   

Abstract

BACKGROUND: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls.
METHODS: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable.
RESULTS: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10-17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 × 10-4). There was evidence of directional pleiotropy (P = 1.5 × 10-4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10-4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS.
CONCLUSIONS: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. IMPACT: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. ©2016 AACR. ©2016 American Association for Cancer Research.

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Year:  2016        PMID: 27550749      PMCID: PMC5093082          DOI: 10.1158/1055-9965.EPI-16-0147

Source DB:  PubMed          Journal:  Cancer Epidemiol Biomarkers Prev        ISSN: 1055-9965            Impact factor:   4.254


  35 in total

1.  Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative.

Authors:  Katherine W Reeves; Gebra Cuyun Carter; Rebecca J Rodabough; Dorothy Lane; S Gene McNeeley; Marcia L Stefanick; Electra D Paskett
Journal:  Gynecol Oncol       Date:  2011-02-15       Impact factor: 5.482

2.  Effect of adiposity and fat distribution on endometrial cancer risk in Shanghai women.

Authors:  Wang Hong Xu; Charles E Matthews; Yong Bing Xiang; Wei Zheng; Zhi Xian Ruan; Jia Rong Cheng; Yu Tang Gao; Xiao Ou Shu
Journal:  Am J Epidemiol       Date:  2005-05-15       Impact factor: 4.897

3.  Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer.

Authors:  C M Nagle; L Marquart; C J Bain; S O'Brien; P H Lahmann; M Quinn; M K Oehler; A Obermair; A B Spurdle; P M Webb
Journal:  Eur J Cancer       Date:  2013-04-11       Impact factor: 9.162

4.  Physical activity, adiposity, and risk of endometrial cancer.

Authors:  Molly B Conroy; Jacob R Sattelmair; Nancy R Cook; JoAnn E Manson; Julie E Buring; I-Min Lee
Journal:  Cancer Causes Control       Date:  2009-02-27       Impact factor: 2.506

5.  Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

Authors:  Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray
Journal:  Int J Cancer       Date:  2014-10-09       Impact factor: 7.396

6.  Association of type 2 diabetes susceptibility variants with advanced prostate cancer risk in the Breast and Prostate Cancer Cohort Consortium.

Authors:  Mitchell J Machiela; Sara Lindström; Naomi E Allen; Christopher A Haiman; Demetrius Albanes; Aurelio Barricarte; Sonja I Berndt; H Bas Bueno-de-Mesquita; Stephen Chanock; J Michael Gaziano; Susan M Gapstur; Edward Giovannucci; Brian E Henderson; Eric J Jacobs; Laurence N Kolonel; Vittorio Krogh; Jing Ma; Meir J Stampfer; Victoria L Stevens; Daniel O Stram; Anne Tjønneland; Ruth Travis; Walter C Willett; David J Hunter; Loic Le Marchand; Peter Kraft
Journal:  Am J Epidemiol       Date:  2012-11-28       Impact factor: 4.897

7.  Genome-wide association study identifies a common variant associated with risk of endometrial cancer.

Authors:  Amanda B Spurdle; Deborah J Thompson; Shahana Ahmed; Kaltin Ferguson; Catherine S Healey; Tracy O'Mara; Logan C Walker; Stephen B Montgomery; Emmanouil T Dermitzakis; Paul Fahey; Grant W Montgomery; Penelope M Webb; Peter A Fasching; Matthias W Beckmann; Arif B Ekici; Alexander Hein; Diether Lambrechts; Lieve Coenegrachts; Ignace Vergote; Frederic Amant; Helga B Salvesen; Jone Trovik; Tormund S Njolstad; Harald Helland; Rodney J Scott; Katie Ashton; Tony Proietto; Geoffrey Otton; Ian Tomlinson; Maggie Gorman; Kimberley Howarth; Shirley Hodgson; Montserrat Garcia-Closas; Nicolas Wentzensen; Hannah Yang; Stephen Chanock; Per Hall; Kamila Czene; Jianjun Liu; Jingmei Li; Xiao-Ou Shu; Wei Zheng; Jirong Long; Yong-Bing Xiang; Mitul Shah; Jonathan Morrison; Kyriaki Michailidou; Paul D Pharoah; Alison M Dunning; Douglas F Easton
Journal:  Nat Genet       Date:  2011-04-17       Impact factor: 38.330

8.  Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition.

Authors:  Christine Friedenreich; Anne Cust; Petra H Lahmann; Karen Steindorf; Marie-Christine Boutron-Ruault; Françoise Clavel-Chapelon; Sylvie Mesrine; Jakob Linseisen; Sabine Rohrmann; Heiner Boeing; Tobias Pischon; Anne Tjønneland; Jytte Halkjaer; Kim Overvad; Michelle Mendez; M L Redondo; Carmen Martinez Garcia; Nerea Larrañaga; María-José Tormo; Aurelio Barricarte Gurrea; Sheila Bingham; Kay-Tee Khaw; Naomi Allen; Tim Key; Antonia Trichopoulou; Effie Vasilopoulou; Dimitrios Trichopoulos; Valeria Pala; Domenico Palli; Rosario Tumino; Amalia Mattiello; Paolo Vineis; H Bas Bueno-de-Mesquita; Petra H M Peeters; Göran Berglund; Jonas Manjer; Eva Lundin; Annekatrin Lukanova; Nadia Slimani; Mazda Jenab; Rudolf Kaaks; Elio Riboli
Journal:  Cancer Causes Control       Date:  2007-02-12       Impact factor: 2.506

9.  Using multiple genetic variants as instrumental variables for modifiable risk factors.

Authors:  Tom M Palmer; Debbie A Lawlor; Roger M Harbord; Nuala A Sheehan; Jon H Tobias; Nicholas J Timpson; George Davey Smith; Jonathan A C Sterne
Journal:  Stat Methods Med Res       Date:  2011-01-07       Impact factor: 3.021

10.  Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.

Authors:  Jennifer Prescott; Veronica W Setiawan; Nicolas Wentzensen; Fredrick Schumacher; Herbert Yu; Ryan Delahanty; Leslie Bernstein; Stephen J Chanock; Chu Chen; Linda S Cook; Christine Friedenreich; Monserrat Garcia-Closas; Christopher A Haiman; Loic Le Marchand; Xiaolin Liang; Jolanta Lissowska; Lingeng Lu; Anthony M Magliocco; Sara H Olson; Harvey A Risch; Xiao-Ou Shu; Giske Ursin; Hannah P Yang; Peter Kraft; Immaculata De Vivo
Journal:  PLoS One       Date:  2015-11-25       Impact factor: 3.240

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  27 in total

1.  Commentary: What can Mendelian randomization tell us about causes of cancer?

Authors:  Daniela Mariosa; Robert Carreras-Torres; Richard M Martin; Mattias Johansson; Paul Brennan
Journal:  Int J Epidemiol       Date:  2019-06-01       Impact factor: 7.196

2.  Adiposity and cancer: a Mendelian randomization analysis in the UK biobank.

Authors:  Muktar Ahmed; Anwar Mulugeta; S Hong Lee; Ville-Petteri Mäkinen; Terry Boyle; Elina Hyppönen
Journal:  Int J Obes (Lond)       Date:  2021-08-27       Impact factor: 5.095

Review 3.  Review of Mendelian Randomization Studies on Endometrial Cancer.

Authors:  Jian-Zeng Guo; Qi-Jun Wu; Fang-Hua Liu; Chang Gao; Ting-Ting Gong; Gang Li
Journal:  Front Endocrinol (Lausanne)       Date:  2022-05-09       Impact factor: 6.055

4.  The Role of Mendelian Randomization Studies in Deciphering the Effect of Obesity on Cancer.

Authors:  Zhe Fang; Mingyang Song; Dong Hoon Lee; Edward L Giovannucci
Journal:  J Natl Cancer Inst       Date:  2022-03-08       Impact factor: 13.506

5.  Mendelian randomization studies of cancer risk: a literature review.

Authors:  Brandon L Pierce; Peter Kraft; Chenan Zhang
Journal:  Curr Epidemiol Rep       Date:  2018-05-18

6.  Harmonisation of biobanking standards in endometrial cancer research.

Authors:  M Adishesh; A Fyson; S B DeCruze; J Kirwan; H M J Werner; D K Hapangama
Journal:  Br J Cancer       Date:  2017-06-29       Impact factor: 7.640

7.  Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting.

Authors:  Isabel Drake; Bo Gullberg; Emily Sonestedt; Tanja Stocks; Anders Bjartell; Elisabet Wirfält; Peter Wallström; Marju Orho-Melander
Journal:  Int J Cancer       Date:  2017-06-24       Impact factor: 7.396

8.  Body mass and cancer: genetics, endocrinology… and more.

Authors:  Lev M Berstein
Journal:  Future Sci OA       Date:  2017-01-20

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

Authors:  Pik-Fang Kho; Frederic Amant; Daniela Annibali; Katie Ashton; John Attia; Paul L Auer; Matthias W Beckmann; Amanda Black; Louise Brinton; Daniel D Buchanan; Stephen J Chanock; Chu Chen; Maxine M Chen; Timothy H T Cheng; Linda S Cook; Marta Crous-Bous; Kamila Czene; Immaculata De Vivo; Joe Dennis; Thilo Dörk; Sean C Dowdy; Alison M Dunning; Matthias Dürst; Douglas F Easton; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Christine M Friedenreich; Montserrat García-Closas; Mia M Gaudet; Graham G Giles; Ellen L Goode; Maggie Gorman; Christopher A Haiman; Per Hall; Susan E Hankinson; Alexander Hein; Peter Hillemanns; Shirley Hodgson; Erling A Hoivik; Elizabeth G Holliday; David J Hunter; Angela Jones; Peter Kraft; Camilla Krakstad; Diether Lambrechts; Loic Le Marchand; Xiaolin Liang; Annika Lindblom; Jolanta Lissowska; Jirong Long; Lingeng Lu; Anthony M Magliocco; Lynn Martin; Mark McEvoy; Roger L Milne; Miriam Mints; Rami Nassir; Geoffrey Otton; Claire Palles; Loreall Pooler; Tony Proietto; Timothy R Rebbeck; Stefan P Renner; Harvey A Risch; Matthias Rübner; Ingo Runnebaum; Carlotta Sacerdote; Gloria E Sarto; Fredrick Schumacher; Rodney J Scott; V Wendy Setiawan; Mitul Shah; Xin Sheng; Xiao-Ou Shu; Melissa C Southey; Emma Tham; Ian Tomlinson; Jone Trovik; Constance Turman; Jonathan P Tyrer; David Van Den Berg; Zhaoming Wang; Nicolas Wentzensen; Lucy Xia; Yong-Bing Xiang; Hannah P Yang; Herbert Yu; Wei Zheng; Penelope M Webb; Deborah J Thompson; Amanda B Spurdle; Dylan M Glubb; Tracy A O'Mara
Journal:  Int J Cancer       Date:  2020-08-07       Impact factor: 7.396

Review 10.  Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

Authors:  Ilkka Kalliala; Georgios Markozannes; Marc J Gunter; Evangelos Paraskevaidis; Hani Gabra; Anita Mitra; Vasso Terzidou; Phillip Bennett; Pierre Martin-Hirsch; Konstantinos K Tsilidis; Maria Kyrgiou
Journal:  BMJ       Date:  2017-10-26
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