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 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. Ausführliche Beschreibung

Gespeichert in:

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]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer

Übergeordnetes Werk:	In: Journal of Translational Medicine - BMC, 2003, 20(2022), 1, Seite 13
Übergeordnetes Werk:	volume:20 ; year:2022 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12967-022-03613-2

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 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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allfields	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
spelling	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
allfields_unstemmed	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
allfieldsGer	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
allfieldsSound	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
language	English
source	In Journal of Translational Medicine 20(2022), 1, Seite 13 volume:20 year:2022 number:1 pages:13
sourceStr	In Journal of Translational Medicine 20(2022), 1, Seite 13 volume:20 year:2022 number:1 pages:13
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer Medicine R
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container_title	Journal of Translational Medicine
authorswithroles_txt_mv	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@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ085020605</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502123835.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230311s2022 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12967-022-03613-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ085020605</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJef000a44851f4e28a8d7423a1ed25890</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Mathias Seviiri</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Melanoma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Melanoma-specific survival</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Polygenic risk score</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genome-wide association study</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Skin cancer</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard A. 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author	Mathias Seviiri
spellingShingle	Mathias Seviiri misc Melanoma misc Melanoma-specific survival misc Polygenic risk score misc Genome-wide association study misc Skin cancer misc Medicine misc R Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
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topic_title	Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting Melanoma Melanoma-specific survival Polygenic risk score Genome-wide association study Skin cancer
topic	misc Melanoma misc Melanoma-specific survival misc Polygenic risk score misc Genome-wide association study misc Skin cancer misc Medicine misc R
topic_unstemmed	misc Melanoma misc Melanoma-specific survival misc Polygenic risk score misc Genome-wide association study misc Skin cancer misc Medicine misc R
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title	Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
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title_full	Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
author_sort	Mathias Seviiri
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author_browse	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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title_sort	higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
title_auth	Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
abstract	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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title_short	Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting
url	https://doi.org/10.1186/s12967-022-03613-2 https://doaj.org/article/ef000a44851f4e28a8d7423a1ed25890 https://doaj.org/toc/1479-5876
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author2Str	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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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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Melanoma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Melanoma-specific survival</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Polygenic risk score</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genome-wide association study</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Skin cancer</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard A. 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Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting

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