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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Veröffentlicht in:Cancer science 2020-12, Vol.111 (12), p.4646-4651
Hauptverfasser: Masuda, Tatsuo, Ogawa, Kotaro, Kamatani, Yoichiro, Murakami, Yoshinori, Kimura, Tadashi, Okada, Yukinori
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container_end_page 4651
container_issue 12
container_start_page 4646
container_title Cancer science
container_volume 111
creator Masuda, Tatsuo
Ogawa, Kotaro
Kamatani, Yoichiro
Murakami, Yoshinori
Kimura, Tadashi
Okada, Yukinori
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.
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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. 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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 &amp; 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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