Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence

Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 indi...
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Autor*in:	Emadeldin Hassanin [verfasserIn] Isabel Spier [verfasserIn] Dheeraj R. Bobbili [verfasserIn] Rana Aldisi [verfasserIn] Hannah Klinkhammer [verfasserIn] Friederike David [verfasserIn] Nuria Dueñas [verfasserIn] Robert Hüneburg [verfasserIn] Claudia Perne [verfasserIn] Joan Brunet [verfasserIn] Gabriel Capella [verfasserIn] Markus M. Nöthen [verfasserIn] Andreas J. Forstner [verfasserIn] Andreas Mayr [verfasserIn] Peter Krawitz [verfasserIn] Patrick May [verfasserIn] Stefan Aretz [verfasserIn] Carlo Maj [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification

Übergeordnetes Werk:	In: BMC Medical Genomics - BMC, 2008, 16(2023), 1, Seite 12
Übergeordnetes Werk:	volume:16 ; year:2023 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12920-023-01469-z

Katalog-ID:	DOAJ087689707

Internformat


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520			\|a Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
650		4	\|a Colorectal cancer
650		4	\|a Family history
650		4	\|a Hereditary cancer
650		4	\|a Polygenic risk
650		4	\|a Risk stratification
653		0	\|a Internal medicine
653		0	\|a Genetics
700	0		\|a Isabel Spier \|e verfasserin \|4 aut
700	0		\|a Dheeraj R. Bobbili \|e verfasserin \|4 aut
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700	0		\|a Hannah Klinkhammer \|e verfasserin \|4 aut
700	0		\|a Friederike David \|e verfasserin \|4 aut
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700	0		\|a Andreas J. Forstner \|e verfasserin \|4 aut
700	0		\|a Andreas Mayr \|e verfasserin \|4 aut
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700	0		\|a Patrick May \|e verfasserin \|4 aut
700	0		\|a Stefan Aretz \|e verfasserin \|4 aut
700	0		\|a Carlo Maj \|e verfasserin \|4 aut
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allfields	10.1186/s12920-023-01469-z doi (DE-627)DOAJ087689707 (DE-599)DOAJ34b301c2174f410ca6f3edd2fefac30e DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Emadeldin Hassanin verfasserin aut Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics Isabel Spier verfasserin aut Dheeraj R. Bobbili verfasserin aut Rana Aldisi verfasserin aut Hannah Klinkhammer verfasserin aut Friederike David verfasserin aut Nuria Dueñas verfasserin aut Robert Hüneburg verfasserin aut Claudia Perne verfasserin aut Joan Brunet verfasserin aut Gabriel Capella verfasserin aut Markus M. Nöthen verfasserin aut Andreas J. Forstner verfasserin aut Andreas Mayr verfasserin aut Peter Krawitz verfasserin aut Patrick May verfasserin aut Stefan Aretz verfasserin aut Carlo Maj verfasserin aut In BMC Medical Genomics BMC, 2008 16(2023), 1, Seite 12 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:16 year:2023 number:1 pages:12 https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e kostenfrei https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 2023 1 12
spelling	10.1186/s12920-023-01469-z doi (DE-627)DOAJ087689707 (DE-599)DOAJ34b301c2174f410ca6f3edd2fefac30e DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Emadeldin Hassanin verfasserin aut Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics Isabel Spier verfasserin aut Dheeraj R. Bobbili verfasserin aut Rana Aldisi verfasserin aut Hannah Klinkhammer verfasserin aut Friederike David verfasserin aut Nuria Dueñas verfasserin aut Robert Hüneburg verfasserin aut Claudia Perne verfasserin aut Joan Brunet verfasserin aut Gabriel Capella verfasserin aut Markus M. Nöthen verfasserin aut Andreas J. Forstner verfasserin aut Andreas Mayr verfasserin aut Peter Krawitz verfasserin aut Patrick May verfasserin aut Stefan Aretz verfasserin aut Carlo Maj verfasserin aut In BMC Medical Genomics BMC, 2008 16(2023), 1, Seite 12 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:16 year:2023 number:1 pages:12 https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e kostenfrei https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 2023 1 12
allfields_unstemmed	10.1186/s12920-023-01469-z doi (DE-627)DOAJ087689707 (DE-599)DOAJ34b301c2174f410ca6f3edd2fefac30e DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Emadeldin Hassanin verfasserin aut Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics Isabel Spier verfasserin aut Dheeraj R. Bobbili verfasserin aut Rana Aldisi verfasserin aut Hannah Klinkhammer verfasserin aut Friederike David verfasserin aut Nuria Dueñas verfasserin aut Robert Hüneburg verfasserin aut Claudia Perne verfasserin aut Joan Brunet verfasserin aut Gabriel Capella verfasserin aut Markus M. Nöthen verfasserin aut Andreas J. Forstner verfasserin aut Andreas Mayr verfasserin aut Peter Krawitz verfasserin aut Patrick May verfasserin aut Stefan Aretz verfasserin aut Carlo Maj verfasserin aut In BMC Medical Genomics BMC, 2008 16(2023), 1, Seite 12 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:16 year:2023 number:1 pages:12 https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e kostenfrei https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 2023 1 12
allfieldsGer	10.1186/s12920-023-01469-z doi (DE-627)DOAJ087689707 (DE-599)DOAJ34b301c2174f410ca6f3edd2fefac30e DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Emadeldin Hassanin verfasserin aut Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics Isabel Spier verfasserin aut Dheeraj R. Bobbili verfasserin aut Rana Aldisi verfasserin aut Hannah Klinkhammer verfasserin aut Friederike David verfasserin aut Nuria Dueñas verfasserin aut Robert Hüneburg verfasserin aut Claudia Perne verfasserin aut Joan Brunet verfasserin aut Gabriel Capella verfasserin aut Markus M. Nöthen verfasserin aut Andreas J. Forstner verfasserin aut Andreas Mayr verfasserin aut Peter Krawitz verfasserin aut Patrick May verfasserin aut Stefan Aretz verfasserin aut Carlo Maj verfasserin aut In BMC Medical Genomics BMC, 2008 16(2023), 1, Seite 12 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:16 year:2023 number:1 pages:12 https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e kostenfrei https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 2023 1 12
allfieldsSound	10.1186/s12920-023-01469-z doi (DE-627)DOAJ087689707 (DE-599)DOAJ34b301c2174f410ca6f3edd2fefac30e DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Emadeldin Hassanin verfasserin aut Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics Isabel Spier verfasserin aut Dheeraj R. Bobbili verfasserin aut Rana Aldisi verfasserin aut Hannah Klinkhammer verfasserin aut Friederike David verfasserin aut Nuria Dueñas verfasserin aut Robert Hüneburg verfasserin aut Claudia Perne verfasserin aut Joan Brunet verfasserin aut Gabriel Capella verfasserin aut Markus M. Nöthen verfasserin aut Andreas J. Forstner verfasserin aut Andreas Mayr verfasserin aut Peter Krawitz verfasserin aut Patrick May verfasserin aut Stefan Aretz verfasserin aut Carlo Maj verfasserin aut In BMC Medical Genomics BMC, 2008 16(2023), 1, Seite 12 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:16 year:2023 number:1 pages:12 https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e kostenfrei https://doi.org/10.1186/s12920-023-01469-z kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 2023 1 12
language	English
source	In BMC Medical Genomics 16(2023), 1, Seite 12 volume:16 year:2023 number:1 pages:12
sourceStr	In BMC Medical Genomics 16(2023), 1, Seite 12 volume:16 year:2023 number:1 pages:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification Internal medicine Genetics
isfreeaccess_bool	true
container_title	BMC Medical Genomics
authorswithroles_txt_mv	Emadeldin Hassanin @@aut@@ Isabel Spier @@aut@@ Dheeraj R. Bobbili @@aut@@ Rana Aldisi @@aut@@ Hannah Klinkhammer @@aut@@ Friederike David @@aut@@ Nuria Dueñas @@aut@@ Robert Hüneburg @@aut@@ Claudia Perne @@aut@@ Joan Brunet @@aut@@ Gabriel Capella @@aut@@ Markus M. Nöthen @@aut@@ Andreas J. Forstner @@aut@@ Andreas Mayr @@aut@@ Peter Krawitz @@aut@@ Patrick May @@aut@@ Stefan Aretz @@aut@@ Carlo Maj @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	559080824
id	DOAJ087689707
language_de	englisch
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Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. 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callnumber-first	R - Medicine
author	Emadeldin Hassanin
spellingShingle	Emadeldin Hassanin misc RC31-1245 misc QH426-470 misc Colorectal cancer misc Family history misc Hereditary cancer misc Polygenic risk misc Risk stratification misc Internal medicine misc Genetics Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
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topic_title	RC31-1245 QH426-470 Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence Colorectal cancer Family history Hereditary cancer Polygenic risk Risk stratification
topic	misc RC31-1245 misc QH426-470 misc Colorectal cancer misc Family history misc Hereditary cancer misc Polygenic risk misc Risk stratification misc Internal medicine misc Genetics
topic_unstemmed	misc RC31-1245 misc QH426-470 misc Colorectal cancer misc Family history misc Hereditary cancer misc Polygenic risk misc Risk stratification misc Internal medicine misc Genetics
topic_browse	misc RC31-1245 misc QH426-470 misc Colorectal cancer misc Family history misc Hereditary cancer misc Polygenic risk misc Risk stratification misc Internal medicine misc Genetics
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title	Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
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title_full	Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
author_sort	Emadeldin Hassanin
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author_browse	Emadeldin Hassanin Isabel Spier Dheeraj R. Bobbili Rana Aldisi Hannah Klinkhammer Friederike David Nuria Dueñas Robert Hüneburg Claudia Perne Joan Brunet Gabriel Capella Markus M. Nöthen Andreas J. Forstner Andreas Mayr Peter Krawitz Patrick May Stefan Aretz Carlo Maj
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title_sort	clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
callnumber	RC31-1245
title_auth	Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
abstract	Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
abstractGer	Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
abstract_unstemmed	Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification. Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (< 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively. Results Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704). Conclusion The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
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title_short	Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
url	https://doi.org/10.1186/s12920-023-01469-z https://doaj.org/article/34b301c2174f410ca6f3edd2fefac30e https://doaj.org/toc/1755-8794
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author2	Isabel Spier Dheeraj R. Bobbili Rana Aldisi Hannah Klinkhammer Friederike David Nuria Dueñas Robert Hüneburg Claudia Perne Joan Brunet Gabriel Capella Markus M. Nöthen Andreas J. Forstner Andreas Mayr Peter Krawitz Patrick May Stefan Aretz Carlo Maj
author2Str	Isabel Spier Dheeraj R. Bobbili Rana Aldisi Hannah Klinkhammer Friederike David Nuria Dueñas Robert Hüneburg Claudia Perne Joan Brunet Gabriel Capella Markus M. Nöthen Andreas J. Forstner Andreas Mayr Peter Krawitz Patrick May Stefan Aretz Carlo Maj
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Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence

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