Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk sco...
Ausführliche Beschreibung
Autor*in: |
Mathias Seviiri [verfasserIn] Richard A. Scolyer [verfasserIn] D. Timothy Bishop [verfasserIn] Julia A. Newton-Bishop [verfasserIn] Mark M. Iles [verfasserIn] Serigne N. Lo [verfasserIn] Johnathan R. Stretch [verfasserIn] Robyn P. M. Saw [verfasserIn] Omgo E. Nieweg [verfasserIn] Kerwin F. Shannon [verfasserIn] Andrew J. Spillane [verfasserIn] Scott D. Gordon [verfasserIn] Catherine M. Olsen [verfasserIn] David C. Whiteman [verfasserIn] Maria Teresa Landi [verfasserIn] John F. Thompson [verfasserIn] Georgina V. Long [verfasserIn] Stuart MacGregor [verfasserIn] Matthew H. Law [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2022 |
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Übergeordnetes Werk: |
In: Journal of Translational Medicine - BMC, 2003, 20(2022), 1, Seite 13 |
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Übergeordnetes Werk: |
volume:20 ; year:2022 ; number:1 ; pages:13 |
Links: |
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DOI / URN: |
10.1186/s12967-022-03613-2 |
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Katalog-ID: |
DOAJ085020605 |
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520 | |a Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. | ||
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700 | 0 | |a Richard A. Scolyer |e verfasserin |4 aut | |
700 | 0 | |a D. Timothy Bishop |e verfasserin |4 aut | |
700 | 0 | |a Julia A. Newton-Bishop |e verfasserin |4 aut | |
700 | 0 | |a Mark M. Iles |e verfasserin |4 aut | |
700 | 0 | |a Serigne N. Lo |e verfasserin |4 aut | |
700 | 0 | |a Johnathan R. Stretch |e verfasserin |4 aut | |
700 | 0 | |a Robyn P. M. Saw |e verfasserin |4 aut | |
700 | 0 | |a Omgo E. Nieweg |e verfasserin |4 aut | |
700 | 0 | |a Kerwin F. Shannon |e verfasserin |4 aut | |
700 | 0 | |a Andrew J. Spillane |e verfasserin |4 aut | |
700 | 0 | |a Scott D. Gordon |e verfasserin |4 aut | |
700 | 0 | |a Catherine M. Olsen |e verfasserin |4 aut | |
700 | 0 | |a David C. Whiteman |e verfasserin |4 aut | |
700 | 0 | |a Maria Teresa Landi |e verfasserin |4 aut | |
700 | 0 | |a John F. Thompson |e verfasserin |4 aut | |
700 | 0 | |a Georgina V. Long |e verfasserin |4 aut | |
700 | 0 | |a Stuart MacGregor |e verfasserin |4 aut | |
700 | 0 | |a Matthew H. Law |e verfasserin |4 aut | |
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10.1186/s12967-022-03613-2 doi (DE-627)DOAJ085020605 (DE-599)DOAJef000a44851f4e28a8d7423a1ed25890 DE-627 ger DE-627 rakwb eng Mathias Seviiri verfasserin aut Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R Richard A. Scolyer verfasserin aut D. Timothy Bishop verfasserin aut Julia A. Newton-Bishop verfasserin aut Mark M. Iles verfasserin aut Serigne N. Lo verfasserin aut Johnathan R. Stretch verfasserin aut Robyn P. M. Saw verfasserin aut Omgo E. Nieweg verfasserin aut Kerwin F. Shannon verfasserin aut Andrew J. Spillane verfasserin aut Scott D. Gordon verfasserin aut Catherine M. Olsen verfasserin aut David C. Whiteman verfasserin aut Maria Teresa Landi verfasserin aut John F. Thompson verfasserin aut Georgina V. Long verfasserin aut Stuart MacGregor verfasserin aut Matthew H. Law verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 kostenfrei https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13 |
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10.1186/s12967-022-03613-2 doi (DE-627)DOAJ085020605 (DE-599)DOAJef000a44851f4e28a8d7423a1ed25890 DE-627 ger DE-627 rakwb eng Mathias Seviiri verfasserin aut Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R Richard A. Scolyer verfasserin aut D. Timothy Bishop verfasserin aut Julia A. Newton-Bishop verfasserin aut Mark M. Iles verfasserin aut Serigne N. Lo verfasserin aut Johnathan R. Stretch verfasserin aut Robyn P. M. Saw verfasserin aut Omgo E. Nieweg verfasserin aut Kerwin F. Shannon verfasserin aut Andrew J. Spillane verfasserin aut Scott D. Gordon verfasserin aut Catherine M. Olsen verfasserin aut David C. Whiteman verfasserin aut Maria Teresa Landi verfasserin aut John F. Thompson verfasserin aut Georgina V. Long verfasserin aut Stuart MacGregor verfasserin aut Matthew H. Law verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 kostenfrei https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13 |
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10.1186/s12967-022-03613-2 doi (DE-627)DOAJ085020605 (DE-599)DOAJef000a44851f4e28a8d7423a1ed25890 DE-627 ger DE-627 rakwb eng Mathias Seviiri verfasserin aut Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R Richard A. Scolyer verfasserin aut D. Timothy Bishop verfasserin aut Julia A. Newton-Bishop verfasserin aut Mark M. Iles verfasserin aut Serigne N. Lo verfasserin aut Johnathan R. Stretch verfasserin aut Robyn P. M. Saw verfasserin aut Omgo E. Nieweg verfasserin aut Kerwin F. Shannon verfasserin aut Andrew J. Spillane verfasserin aut Scott D. Gordon verfasserin aut Catherine M. Olsen verfasserin aut David C. Whiteman verfasserin aut Maria Teresa Landi verfasserin aut John F. Thompson verfasserin aut Georgina V. Long verfasserin aut Stuart MacGregor verfasserin aut Matthew H. Law verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 kostenfrei https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13 |
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10.1186/s12967-022-03613-2 doi (DE-627)DOAJ085020605 (DE-599)DOAJef000a44851f4e28a8d7423a1ed25890 DE-627 ger DE-627 rakwb eng Mathias Seviiri verfasserin aut Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R Richard A. Scolyer verfasserin aut D. Timothy Bishop verfasserin aut Julia A. Newton-Bishop verfasserin aut Mark M. Iles verfasserin aut Serigne N. Lo verfasserin aut Johnathan R. Stretch verfasserin aut Robyn P. M. Saw verfasserin aut Omgo E. Nieweg verfasserin aut Kerwin F. Shannon verfasserin aut Andrew J. Spillane verfasserin aut Scott D. Gordon verfasserin aut Catherine M. Olsen verfasserin aut David C. Whiteman verfasserin aut Maria Teresa Landi verfasserin aut John F. Thompson verfasserin aut Georgina V. Long verfasserin aut Stuart MacGregor verfasserin aut Matthew H. Law verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 kostenfrei https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13 |
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10.1186/s12967-022-03613-2 doi (DE-627)DOAJ085020605 (DE-599)DOAJef000a44851f4e28a8d7423a1ed25890 DE-627 ger DE-627 rakwb eng Mathias Seviiri verfasserin aut Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R Richard A. Scolyer verfasserin aut D. Timothy Bishop verfasserin aut Julia A. Newton-Bishop verfasserin aut Mark M. Iles verfasserin aut Serigne N. Lo verfasserin aut Johnathan R. Stretch verfasserin aut Robyn P. M. Saw verfasserin aut Omgo E. Nieweg verfasserin aut Kerwin F. Shannon verfasserin aut Andrew J. Spillane verfasserin aut Scott D. Gordon verfasserin aut Catherine M. Olsen verfasserin aut David C. Whiteman verfasserin aut Maria Teresa Landi verfasserin aut John F. Thompson verfasserin aut Georgina V. Long verfasserin aut Stuart MacGregor verfasserin aut Matthew H. Law verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 kostenfrei https://doi.org/10.1186/s12967-022-03613-2 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13 |
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Mathias Seviiri @@aut@@ Richard A. Scolyer @@aut@@ D. Timothy Bishop @@aut@@ Julia A. Newton-Bishop @@aut@@ Mark M. Iles @@aut@@ Serigne N. Lo @@aut@@ Johnathan R. Stretch @@aut@@ Robyn P. M. Saw @@aut@@ Omgo E. Nieweg @@aut@@ Kerwin F. Shannon @@aut@@ Andrew J. Spillane @@aut@@ Scott D. Gordon @@aut@@ Catherine M. Olsen @@aut@@ David C. Whiteman @@aut@@ Maria Teresa Landi @@aut@@ John F. Thompson @@aut@@ Georgina V. Long @@aut@@ Stuart MacGregor @@aut@@ Matthew H. Law @@aut@@ |
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Mathias Seviiri Richard A. Scolyer D. Timothy Bishop Julia A. Newton-Bishop Mark M. Iles Serigne N. Lo Johnathan R. Stretch Robyn P. M. Saw Omgo E. Nieweg Kerwin F. Shannon Andrew J. Spillane Scott D. Gordon Catherine M. Olsen David C. Whiteman Maria Teresa Landi John F. Thompson Georgina V. Long Stuart MacGregor Matthew H. Law |
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higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting |
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Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting |
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Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. |
abstractGer |
Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. |
abstract_unstemmed |
Abstract Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting. |
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Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting |
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