Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk
Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy co...
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| Veröffentlicht in: | Molecular carcinogenesis 2021-11, Vol.60 (11), p.726-733 |
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| creator | Tsai, Chia‐Wen Chang, Wen‐Shin Xu, Yifan Huang, Maosheng Bau, Da‐Tian Gu, Jian |
| description | Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54–0.82, p |
| doi_str_mv | 10.1002/mc.23334 |
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The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54–0.82, p < 0.001). We then used a summary statistics‐based MR method, inverse‐variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54–0.83, p < 0.001). When we categorized individuals into high and low IGF‐1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70–0.89) compared to the low GRS group. Genetically predicted circulating IGFBP‐3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF‐1 level and bladder cancer risk.</description><identifier>ISSN: 0899-1987</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.23334</identifier><identifier>PMID: 34293213</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; Bladder cancer ; Cancer ; Carcinogenesis ; Case-Control Studies ; Female ; Genetic Association Studies ; Genetic diversity ; Genetic Predisposition to Disease ; genetic risk score ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Growth factors ; Humans ; IGF‐1 ; Insulin ; Insulin-Like Growth Factor Binding Protein 3 - blood ; Insulin-Like Growth Factor Binding Protein 3 - genetics ; Insulin-Like Growth Factor I - genetics ; Insulin-Like Growth Factor I - metabolism ; Insulin-like growth factors ; Male ; Mendelian randomization ; Mendelian Randomization Analysis - methods ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk factors ; Single-nucleotide polymorphism ; SNP ; Urinary Bladder Neoplasms - blood ; Urinary Bladder Neoplasms - genetics</subject><ispartof>Molecular carcinogenesis, 2021-11, Vol.60 (11), p.726-733</ispartof><rights>2021 Wiley Periodicals LLC</rights><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3494-1ffc2d664703518a16f89f0795bb75c149b05d0054049d57f85b75de0f0ea7303</citedby><cites>FETCH-LOGICAL-c3494-1ffc2d664703518a16f89f0795bb75c149b05d0054049d57f85b75de0f0ea7303</cites><orcidid>0000-0003-3499-0973</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmc.23334$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmc.23334$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34293213$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Chia‐Wen</creatorcontrib><creatorcontrib>Chang, Wen‐Shin</creatorcontrib><creatorcontrib>Xu, Yifan</creatorcontrib><creatorcontrib>Huang, Maosheng</creatorcontrib><creatorcontrib>Bau, Da‐Tian</creatorcontrib><creatorcontrib>Gu, Jian</creatorcontrib><title>Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk</title><title>Molecular carcinogenesis</title><addtitle>Mol Carcinog</addtitle><description>Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54–0.82, p < 0.001). We then used a summary statistics‐based MR method, inverse‐variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54–0.83, p < 0.001). When we categorized individuals into high and low IGF‐1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70–0.89) compared to the low GRS group. Genetically predicted circulating IGFBP‐3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF‐1 level and bladder cancer risk.</description><subject>Aged</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Association Studies</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>genetic risk score</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>IGF‐1</subject><subject>Insulin</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - blood</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - genetics</subject><subject>Insulin-Like Growth Factor I - genetics</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Insulin-like growth factors</subject><subject>Male</subject><subject>Mendelian randomization</subject><subject>Mendelian Randomization Analysis - methods</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk factors</subject><subject>Single-nucleotide polymorphism</subject><subject>SNP</subject><subject>Urinary Bladder Neoplasms - blood</subject><subject>Urinary Bladder Neoplasms - genetics</subject><issn>0899-1987</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtOwzAQhi0EglKQOAGyxIZNyji2m3hZVbykIjawjhw_iiF1ip2o6o4jcATOxkkwFNjBaqR_Pn0zmkHoiMCIAORnCzXKKaVsCw0IiDLLC8a20QBKITIiymIP7cf4CEBIwWEX7VGWC5oTOkBvkxhb5WTnWh9xa_HceNM5JZtmjZfBaKc6o7FyQfVNovwcOx_7xvn3l9fGPRk8D-2qe8BWqq4NKSRYev0vhGvn9adpGdrOfEEUr1zq143U2gSspFepBBefDtCOlU00h991iO4vzu-mV9ns9vJ6OpllijLBMmKtyvV4zAqgnJSSjG0pLBSC13XBFWGiBq4BOAMmNC9syVOuDVgwsqBAh-hk401LPfcmdtVj2wefRlY5L0nJGWE0UacbSoU2xmBstQxuIcO6IlB9vqJaqOrrFQk9_hb29cLoX_Dn9gnINsDKNWb9p6i6mW6EH05yl-0</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Tsai, Chia‐Wen</creator><creator>Chang, Wen‐Shin</creator><creator>Xu, Yifan</creator><creator>Huang, Maosheng</creator><creator>Bau, Da‐Tian</creator><creator>Gu, Jian</creator><general>Wiley Subscription Services, Inc</general><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>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0003-3499-0973</orcidid></search><sort><creationdate>202111</creationdate><title>Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk</title><author>Tsai, Chia‐Wen ; Chang, Wen‐Shin ; Xu, Yifan ; Huang, Maosheng ; Bau, Da‐Tian ; Gu, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3494-1ffc2d664703518a16f89f0795bb75c149b05d0054049d57f85b75de0f0ea7303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Association Studies</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>genetic risk score</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>IGF‐1</topic><topic>Insulin</topic><topic>Insulin-Like Growth Factor Binding Protein 3 - blood</topic><topic>Insulin-Like Growth Factor Binding Protein 3 - genetics</topic><topic>Insulin-Like Growth Factor I - genetics</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Insulin-like growth factors</topic><topic>Male</topic><topic>Mendelian randomization</topic><topic>Mendelian Randomization Analysis - methods</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk factors</topic><topic>Single-nucleotide polymorphism</topic><topic>SNP</topic><topic>Urinary Bladder Neoplasms - blood</topic><topic>Urinary Bladder Neoplasms - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Chia‐Wen</creatorcontrib><creatorcontrib>Chang, Wen‐Shin</creatorcontrib><creatorcontrib>Xu, Yifan</creatorcontrib><creatorcontrib>Huang, Maosheng</creatorcontrib><creatorcontrib>Bau, Da‐Tian</creatorcontrib><creatorcontrib>Gu, Jian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Chia‐Wen</au><au>Chang, Wen‐Shin</au><au>Xu, Yifan</au><au>Huang, Maosheng</au><au>Bau, Da‐Tian</au><au>Gu, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk</atitle><jtitle>Molecular carcinogenesis</jtitle><addtitle>Mol Carcinog</addtitle><date>2021-11</date><risdate>2021</risdate><volume>60</volume><issue>11</issue><spage>726</spage><epage>733</epage><pages>726-733</pages><issn>0899-1987</issn><eissn>1098-2744</eissn><abstract>Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54–0.82, p < 0.001). We then used a summary statistics‐based MR method, inverse‐variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54–0.83, p < 0.001). When we categorized individuals into high and low IGF‐1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70–0.89) compared to the low GRS group. Genetically predicted circulating IGFBP‐3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF‐1 level and bladder cancer risk.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34293213</pmid><doi>10.1002/mc.23334</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3499-0973</orcidid></addata></record> |
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| subjects | Aged Bladder cancer Cancer Carcinogenesis Case-Control Studies Female Genetic Association Studies Genetic diversity Genetic Predisposition to Disease genetic risk score Genome-wide association studies Genome-Wide Association Study Genomes Growth factors Humans IGF‐1 Insulin Insulin-Like Growth Factor Binding Protein 3 - blood Insulin-Like Growth Factor Binding Protein 3 - genetics Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - metabolism Insulin-like growth factors Male Mendelian randomization Mendelian Randomization Analysis - methods Middle Aged Polymorphism, Single Nucleotide Risk factors Single-nucleotide polymorphism SNP Urinary Bladder Neoplasms - blood Urinary Bladder Neoplasms - genetics |
| title | Associations of genetically predicted circulating insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 with bladder cancer risk |
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