A Mendelian randomization study identified obesity as a causal risk factor of uterine endometrial cancer in Japanese
Causal inference is one of the challenges in epidemiologic studies. Gynecologic diseases have been reported to have association with obesity, however the causality remained controversial except for uterine endometrial cancer. We conducted two‐sample Mendelian randomization (MR) analysis using the la...
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description | Causal inference is one of the challenges in epidemiologic studies. Gynecologic diseases have been reported to have association with obesity, however the causality remained controversial except for uterine endometrial cancer. We conducted two‐sample Mendelian randomization (MR) analysis using the large‐scale genome‐wide association study (GWAS) results of gynecologic diseases and body mass index (BMI) in the Japanese population to assess causal effect of BMI on gynecologic diseases. We first conducted GWAS of ovarian cancer, uterine endometrial cancer, uterine cervical cancer, endometriosis, and uterine fibroid (n = 647, 909, 538, 5236, and 645 cases, respectively, and 39 556 shared female controls), and BMI (81 610 males and non‐overlapping 23 924 females). We then applied two‐sample MR using 74 BMI‐associated variants as instrumental variables. We observed significant causal effect of increased BMI on uterine endometrial cancer (β = 0.735, P = .0010 in inverse variance‐weighted analysis), which is concordant with results of European studies. Causal effect of obesity was not apparent in the other gynecologic diseases tested. Our MR analyses provided strong evidence of the causal role of obesity in gynecologic diseases etiology, and suggested a possible preventive effect of intervention for obesity.
We assessed whether obesity is causally associated with gynecologic diseases or not. We performed a Mendelian randomization study and revealed that obesity assessed by measurement of body mass index is causally associated with uterine endometrial cancer in Japanese. Intervention to reduce body weight may prevent uterine endometrial cancer. |
doi_str_mv | 10.1111/cas.14667 |
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We assessed whether obesity is causally associated with gynecologic diseases or not. We performed a Mendelian randomization study and revealed that obesity assessed by measurement of body mass index is causally associated with uterine endometrial cancer in Japanese. Intervention to reduce body weight may prevent uterine endometrial cancer.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14667</identifier><identifier>PMID: 32981178</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Biobanks ; BMI ; Body Mass Index ; Cancer ; Case-Control Studies ; Causality ; Cervical cancer ; Cervix ; Consortia ; Development and progression ; Disease ; Endometrial cancer ; Endometrial Neoplasms - genetics ; Endometriosis ; Endometriosis - etiology ; Endometriosis - genetics ; Endometrium ; Epidemiology ; Etiology ; Female ; Females ; Fibroids ; Generalized linear models ; Genital Neoplasms, Female - genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; GWAS ; gynecologic diseases ; Humans ; Japan ; Leiomyoma - genetics ; Mendelian randomization ; Mendelian Randomization Analysis - methods ; Obesity ; Obesity - complications ; Obesity - genetics ; Oncology, Experimental ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Population ; Reproducibility of Results ; Risk Factors ; Standard deviation ; Uterine cancer ; Uterine Cervical Neoplasms - genetics ; Uterine Neoplasms - genetics ; Uterus</subject><ispartof>Cancer science, 2020-12, Vol.111 (12), p.4646-4651</ispartof><rights>2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association</rights><rights>2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6287-7ee723098494021e76cdd5c4e97680a6ff63fe20fe3ad6869ba329afc476aa923</citedby><cites>FETCH-LOGICAL-c6287-7ee723098494021e76cdd5c4e97680a6ff63fe20fe3ad6869ba329afc476aa923</cites><orcidid>0000-0002-0311-8472 ; 0000-0002-2826-4396</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734162/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734162/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11542,27903,27904,45553,45554,46030,46454,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32981178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Masuda, Tatsuo</creatorcontrib><creatorcontrib>Ogawa, Kotaro</creatorcontrib><creatorcontrib>Kamatani, Yoichiro</creatorcontrib><creatorcontrib>Murakami, Yoshinori</creatorcontrib><creatorcontrib>Kimura, Tadashi</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><title>A Mendelian randomization study identified obesity as a causal risk factor of uterine endometrial cancer in Japanese</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Causal inference is one of the challenges in epidemiologic studies. Gynecologic diseases have been reported to have association with obesity, however the causality remained controversial except for uterine endometrial cancer. We conducted two‐sample Mendelian randomization (MR) analysis using the large‐scale genome‐wide association study (GWAS) results of gynecologic diseases and body mass index (BMI) in the Japanese population to assess causal effect of BMI on gynecologic diseases. We first conducted GWAS of ovarian cancer, uterine endometrial cancer, uterine cervical cancer, endometriosis, and uterine fibroid (n = 647, 909, 538, 5236, and 645 cases, respectively, and 39 556 shared female controls), and BMI (81 610 males and non‐overlapping 23 924 females). We then applied two‐sample MR using 74 BMI‐associated variants as instrumental variables. We observed significant causal effect of increased BMI on uterine endometrial cancer (β = 0.735, P = .0010 in inverse variance‐weighted analysis), which is concordant with results of European studies. Causal effect of obesity was not apparent in the other gynecologic diseases tested. Our MR analyses provided strong evidence of the causal role of obesity in gynecologic diseases etiology, and suggested a possible preventive effect of intervention for obesity.
We assessed whether obesity is causally associated with gynecologic diseases or not. We performed a Mendelian randomization study and revealed that obesity assessed by measurement of body mass index is causally associated with uterine endometrial cancer in Japanese. Intervention to reduce body weight may prevent uterine endometrial cancer.</description><subject>Biobanks</subject><subject>BMI</subject><subject>Body Mass Index</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Causality</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Consortia</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Endometrial cancer</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometriosis</subject><subject>Endometriosis - etiology</subject><subject>Endometriosis - genetics</subject><subject>Endometrium</subject><subject>Epidemiology</subject><subject>Etiology</subject><subject>Female</subject><subject>Females</subject><subject>Fibroids</subject><subject>Generalized linear models</subject><subject>Genital Neoplasms, Female - genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>GWAS</subject><subject>gynecologic diseases</subject><subject>Humans</subject><subject>Japan</subject><subject>Leiomyoma - genetics</subject><subject>Mendelian randomization</subject><subject>Mendelian Randomization Analysis - methods</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>Obesity - genetics</subject><subject>Oncology, Experimental</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Population</subject><subject>Reproducibility of Results</subject><subject>Risk Factors</subject><subject>Standard deviation</subject><subject>Uterine cancer</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Neoplasms - genetics</subject><subject>Uterus</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kk1vEzEQhlcIREvhwB9AlrjAYVN_7NrrC1IU8akiDsDZmtjj4rKxg70LCr8epylViwD7YMt-5p15R9M0jxldsLpOLZQF66RUd5pjJjrdKkrl3cu7ajUV_Kh5UMoFpUJ2urvfHAmuB8bUcNxMS_Ieo8MxQCQZokub8BOmkCIp0-x2JDiMU_ABHUlrLGHaESgEiIW5wEhyKF-JBzulTJIn84Q5RCS4F8Iph4pYiBYzCZG8gy1ELPiwuedhLPjo6jxpPr96-Wn1pj378PrtannWWskH1SpExQXVQy2acoZKWud626FWcqAgvZfCI6ceBTg5SL2Gagy87ZQE0FycNC8Outt5vUFnq5MMo9nmsIG8MwmCuf0Twxdznr4bpUTH5F7g2ZVATt9mLJPZhGJxHKuNNBfDu05qLamgFX36B3qR5hyrPcP7nteSue7-S1UpqWnPb2idw4gmRJ9qdXaf2iwVo6qniolKLf5C1e1wE2yK6EN9vxXw_BBgcyolo7_uBKNmP0imDpK5HKTKPrnZumvy9-RU4PQA_KhZdv9WMqvlx4PkL5FG0WA</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Masuda, Tatsuo</creator><creator>Ogawa, Kotaro</creator><creator>Kamatani, Yoichiro</creator><creator>Murakami, Yoshinori</creator><creator>Kimura, Tadashi</creator><creator>Okada, Yukinori</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0311-8472</orcidid><orcidid>https://orcid.org/0000-0002-2826-4396</orcidid></search><sort><creationdate>202012</creationdate><title>A Mendelian randomization study identified obesity as a causal risk factor of uterine endometrial cancer in Japanese</title><author>Masuda, Tatsuo ; Ogawa, Kotaro ; Kamatani, Yoichiro ; Murakami, Yoshinori ; Kimura, Tadashi ; Okada, Yukinori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6287-7ee723098494021e76cdd5c4e97680a6ff63fe20fe3ad6869ba329afc476aa923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biobanks</topic><topic>BMI</topic><topic>Body Mass Index</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>Causality</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Consortia</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Endometrial cancer</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometriosis</topic><topic>Endometriosis - etiology</topic><topic>Endometriosis - genetics</topic><topic>Endometrium</topic><topic>Epidemiology</topic><topic>Etiology</topic><topic>Female</topic><topic>Females</topic><topic>Fibroids</topic><topic>Generalized linear models</topic><topic>Genital Neoplasms, Female - genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics</topic><topic>GWAS</topic><topic>gynecologic diseases</topic><topic>Humans</topic><topic>Japan</topic><topic>Leiomyoma - genetics</topic><topic>Mendelian randomization</topic><topic>Mendelian Randomization Analysis - methods</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>Obesity - genetics</topic><topic>Oncology, Experimental</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Population</topic><topic>Reproducibility of Results</topic><topic>Risk Factors</topic><topic>Standard deviation</topic><topic>Uterine cancer</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Neoplasms - genetics</topic><topic>Uterus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masuda, Tatsuo</creatorcontrib><creatorcontrib>Ogawa, Kotaro</creatorcontrib><creatorcontrib>Kamatani, Yoichiro</creatorcontrib><creatorcontrib>Murakami, Yoshinori</creatorcontrib><creatorcontrib>Kimura, Tadashi</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masuda, Tatsuo</au><au>Ogawa, Kotaro</au><au>Kamatani, Yoichiro</au><au>Murakami, Yoshinori</au><au>Kimura, Tadashi</au><au>Okada, Yukinori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Mendelian randomization study identified obesity as a causal risk factor of uterine endometrial cancer in Japanese</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2020-12</date><risdate>2020</risdate><volume>111</volume><issue>12</issue><spage>4646</spage><epage>4651</epage><pages>4646-4651</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Causal inference is one of the challenges in epidemiologic studies. Gynecologic diseases have been reported to have association with obesity, however the causality remained controversial except for uterine endometrial cancer. We conducted two‐sample Mendelian randomization (MR) analysis using the large‐scale genome‐wide association study (GWAS) results of gynecologic diseases and body mass index (BMI) in the Japanese population to assess causal effect of BMI on gynecologic diseases. We first conducted GWAS of ovarian cancer, uterine endometrial cancer, uterine cervical cancer, endometriosis, and uterine fibroid (n = 647, 909, 538, 5236, and 645 cases, respectively, and 39 556 shared female controls), and BMI (81 610 males and non‐overlapping 23 924 females). We then applied two‐sample MR using 74 BMI‐associated variants as instrumental variables. We observed significant causal effect of increased BMI on uterine endometrial cancer (β = 0.735, P = .0010 in inverse variance‐weighted analysis), which is concordant with results of European studies. Causal effect of obesity was not apparent in the other gynecologic diseases tested. Our MR analyses provided strong evidence of the causal role of obesity in gynecologic diseases etiology, and suggested a possible preventive effect of intervention for obesity.
We assessed whether obesity is causally associated with gynecologic diseases or not. We performed a Mendelian randomization study and revealed that obesity assessed by measurement of body mass index is causally associated with uterine endometrial cancer in Japanese. Intervention to reduce body weight may prevent uterine endometrial cancer.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32981178</pmid><doi>10.1111/cas.14667</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-0311-8472</orcidid><orcidid>https://orcid.org/0000-0002-2826-4396</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biobanks BMI Body Mass Index Cancer Case-Control Studies Causality Cervical cancer Cervix Consortia Development and progression Disease Endometrial cancer Endometrial Neoplasms - genetics Endometriosis Endometriosis - etiology Endometriosis - genetics Endometrium Epidemiology Etiology Female Females Fibroids Generalized linear models Genital Neoplasms, Female - genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics GWAS gynecologic diseases Humans Japan Leiomyoma - genetics Mendelian randomization Mendelian Randomization Analysis - methods Obesity Obesity - complications Obesity - genetics Oncology, Experimental Ovarian cancer Ovarian Neoplasms - genetics Population Reproducibility of Results Risk Factors Standard deviation Uterine cancer Uterine Cervical Neoplasms - genetics Uterine Neoplasms - genetics Uterus |
title | A Mendelian randomization study identified obesity as a causal risk factor of uterine endometrial cancer in Japanese |
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