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Article: Body mass index and type 2 diabetes and breast cancer survival: a Mendelian randomization study

TitleBody mass index and type 2 diabetes and breast cancer survival: a Mendelian randomization study
Authors
KeywordsMendelian randomization
Body mass index
Breast cancer progression
Breast cancer survival analysis
Type 2 diabetes
Issue Date2021
Publishere-Century Pub. Corp.. The Journal's web site is located at http://www.ajcr.us
Citation
American Journal of Cancer Research, 2021, v. 11 n. 8, p. 3921-3934 How to Cite?
AbstractThe causal relationship between body mass index (BMI) and type 2 diabetes (T2D) and breast cancer prognosis is still ambiguous. The aim of this study was to investigate the prognostic effect of BMI and T2D on breast cancer disease-free survival (DFS) among Asian individuals. In this two-sample Mendelian randomization (MR) study, the instrumental variables (IVs) were identified using a genome-wide association study (GWAS) among 24,000 participants in the Taiwan Biobank. Importantly, the validity of these IVs was confirmed with a previous large-scale GWAS (Biobank Japan Project, BBJ). In this study, we found that a genetic predisposition toward higher BMI (as indicated by BMI IVs, F = 86.88) was associated with poor breast cancer DFS (hazard ratio [HR] = 6.11; P < 0.001). Furthermore, higher level of genetically predicted T2D (as indicated by T2D IVs) was associated with an increased risk of recurrence of and mortality from breast cancer (HR = 1.43; P < 0.001). Sensitivity analyses, including the weighted-median approach, MR-Egger regression, Radial regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) supported the consistency of our findings. Finally, the causal relationship between BMI and poor breast cancer prognosis was confirmed in a prospective cohort study. Our MR analyses demonstrated the causal relationship between the genetic prediction of elevated BMI and a greater risk of T2D with poor breast cancer prognosis. BMI and T2D have important clinical implications and may be used as prognostic indicators of breast cancer.
Persistent Identifierhttp://hdl.handle.net/10722/304763
ISSN
2023 Impact Factor: 3.6
2019 SCImago Journal Rankings: 1.562
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, YS-
dc.contributor.authorChou, WC-
dc.contributor.authorVikram, R-
dc.contributor.authorChen, WT-
dc.contributor.authorYang, SL-
dc.contributor.authorBolla, MK-
dc.contributor.authorWang, Q-
dc.contributor.authorDennis, J-
dc.contributor.authorChan, TL-
dc.contributor.authorChoi, JY-
dc.contributor.authorHou, MF-
dc.contributor.authorIto, H-
dc.contributor.authorKang, D-
dc.contributor.authorKim, SW-
dc.contributor.authorKwong, A-
dc.contributor.authorMatsuo, K-
dc.contributor.authorPark, SK-
dc.contributor.authorWu, P-
dc.contributor.authorShu, XO-
dc.contributor.authorZheng, W-
dc.contributor.authorDunning, AM-
dc.contributor.authorEaston, DF-
dc.contributor.authorShen, CY-
dc.date.accessioned2021-10-05T02:34:50Z-
dc.date.available2021-10-05T02:34:50Z-
dc.date.issued2021-
dc.identifier.citationAmerican Journal of Cancer Research, 2021, v. 11 n. 8, p. 3921-3934-
dc.identifier.issn2156-6976-
dc.identifier.urihttp://hdl.handle.net/10722/304763-
dc.description.abstractThe causal relationship between body mass index (BMI) and type 2 diabetes (T2D) and breast cancer prognosis is still ambiguous. The aim of this study was to investigate the prognostic effect of BMI and T2D on breast cancer disease-free survival (DFS) among Asian individuals. In this two-sample Mendelian randomization (MR) study, the instrumental variables (IVs) were identified using a genome-wide association study (GWAS) among 24,000 participants in the Taiwan Biobank. Importantly, the validity of these IVs was confirmed with a previous large-scale GWAS (Biobank Japan Project, BBJ). In this study, we found that a genetic predisposition toward higher BMI (as indicated by BMI IVs, F = 86.88) was associated with poor breast cancer DFS (hazard ratio [HR] = 6.11; P < 0.001). Furthermore, higher level of genetically predicted T2D (as indicated by T2D IVs) was associated with an increased risk of recurrence of and mortality from breast cancer (HR = 1.43; P < 0.001). Sensitivity analyses, including the weighted-median approach, MR-Egger regression, Radial regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) supported the consistency of our findings. Finally, the causal relationship between BMI and poor breast cancer prognosis was confirmed in a prospective cohort study. Our MR analyses demonstrated the causal relationship between the genetic prediction of elevated BMI and a greater risk of T2D with poor breast cancer prognosis. BMI and T2D have important clinical implications and may be used as prognostic indicators of breast cancer.-
dc.languageeng-
dc.publishere-Century Pub. Corp.. The Journal's web site is located at http://www.ajcr.us-
dc.relation.ispartofAmerican Journal of Cancer Research-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectMendelian randomization-
dc.subjectBody mass index-
dc.subjectBreast cancer progression-
dc.subjectBreast cancer survival analysis-
dc.subjectType 2 diabetes-
dc.titleBody mass index and type 2 diabetes and breast cancer survival: a Mendelian randomization study-
dc.typeArticle-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityChan, TL=rp00418-
dc.identifier.authorityKwong, A=rp01734-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid34522458-
dc.identifier.pmcidPMC8414374-
dc.identifier.hkuros326264-
dc.identifier.volume11-
dc.identifier.issue8-
dc.identifier.spage3921-
dc.identifier.epage3934-
dc.publisher.placeUnited States-

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