BRST5:The polygenic component of breast cancer susceptibility - Revision history

Lynn.Hu: /* Genetic Abnormalities: Germline */

2025-06-28T15:10:28Z

Genetic Abnormalities: Germline

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	!Notes		!Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> ''BRCA1''~~\|\|~~<span class="blue-text"~~>~~EXAMPLE:</span> Many~~\|\|~~<span class="blue-text">EXAMPLE:<~~/~~span> Multiple variant types leading to loss of function~~\|\|~~<span class="blue~~-~~text">EXAMPLE~~:<~~/span> Autosomal recessive~~,		\|Multiple Genes(FGFR2, MAP3K1, TOX3 etc)\|\|Many SNPs (Common, minor allele frequency >1%)\|\|Affect regulatory region or epigenetics rather than traditional oncogenes/tumor suppressor genes \|\|complex inheritance: non-Mendelian, polygenic pattern; their effects are additive or multiplicative and are often influenced by environment; Penetrance: each SNP confer very modest risk (<1.3 fold), but cumulative penetrance increases with a higher PRS; Expressivity: variable. PRS may influence age of onset, tumor subtype or morphology
	~~~30% penetrant for carriers~~
	\|		\|
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> Gene X~~		\|
	\|~~<span class="blue-text">EXAMPLE:</span> List the specific mutation~~		\|
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	!Notes		!Notes
	\|-		\|-
	\|~~Multiple SNPs (e.g., FGFR2, MAP3K1, TOX3)~~		\|
	\|Regulatory/epigenetic, not traditional oncogenes/TSGs		\|Regulatory/epigenetic, not traditional oncogenes/TSGs
	\|Common, MAF >1%		\|Common, MAF >1%
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	!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome		!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
	\|-		\|-
	\|''~~MAP2K1~~''~~; ???~~		\|''MAP3K1''
	\|~~ERK1~~/~~2 cascade~~		\|MAPK/ERK pathway
	\|~~Altered~~ signal transduction		\|Alters cell survival and signal transduction
	\|-		\|-
	\|''FGFR2''~~; ???~~		\|''FGFR2''
	\|FGF signaling		\|FGF signaling
	\|~~Enhanced cell~~ proliferation		\|Increases proliferation
	\|-		\|-
	\|''TOX3''~~; ???~~		\|''TOX3''
	\|~~Transcriptional regulation~~		\|Chromatin remodeling
	\|Affects ~~chromatin remodeling~~		\|Affects transcriptional regulation and stress response
	\|-		\|-
	\|''ESR1''~~; ???~~		\|''ESR1''
	\|Estrogen signaling		\|Estrogen receptor signaling
	\|~~Influences hormone~~ response in ~~breast cancer~~		\|Modulates hormonal response in luminal cells
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations~~		\|CDKN2B
	\|~~<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling~~		\|Cell cycle checkpoint
	\|~~<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program~~		\|Dysregulates cell cycle progression
	\|}		\|}
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Jennelleh: Jennelleh moved page BRST5:BRST5:The polygenic component of breast cancer susceptibility to BRST5:The polygenic component of breast cancer susceptibility without leaving a redirect

2025-06-22T18:56:18Z

Jennelleh moved page BRST5:BRST5:The polygenic component of breast cancer susceptibility to BRST5:The polygenic component of breast cancer susceptibility without leaving a redirect

← Older revision	Revision as of 13:56, 22 June 2025
(No difference)

Jennelleh: Jennelleh moved page BRST5:Polygenic component of breast cancer susceptibility to BRST5:BRST5:The polygenic component of breast cancer susceptibility without leaving a redirect

2025-06-22T18:55:50Z

Jennelleh moved page BRST5:Polygenic component of breast cancer susceptibility to BRST5:BRST5:The polygenic component of breast cancer susceptibility without leaving a redirect

← Older revision	Revision as of 13:55, 22 June 2025
(No difference)

Jennelleh at 18:53, 22 June 2025

2025-06-22T18:53:35Z

← Older revision		Revision as of 13:53, 22 June 2025
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	\|-		\|-
	\|Book		\|Book
	\|		\|Breast Tumours (5th ed.)
	\|-		\|-
	\|Category		\|Category
	\|		\|Genetic tumour syndromes of the breast
	\|-		\|-
	\|Family		\|Family
	\|		\|Syndromes
	\|-		\|-
	\|Type		\|Type
	\|		\|Polygenetic component of breast cancer susceptibility
	\|-		\|-
	\|Subtype(s)		\|Subtype(s)
	\|		\|N/A
	\|}		\|}

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	\|Acceptable		\|Acceptable
	\|		\|N/A
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}
	Polygenic breast cancer risk; Common low-penetrance breast cancer alleles		Polygenic breast cancer risk; Common low-penetrance breast cancer alleles
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	\|}		\|}
	~~{\| class="wikitable sortable"~~		'''PLEASE PUT CONTENT FROM OLD TABLE BELOW WHERE YOU WANT IT AND THEN DELETE THE OLD TABLE.'''
	\|-
	~~!Gene; Genetic Alteration!!~~'''~~Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!~~'''~~Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''~~
	~~!'''Diagnostic Significance (Yes, No or Unknown)'''~~
	~~!Prognostic Significance (Yes, No or Unknown)~~
	~~!Therapeutic Significance (Yes, No or Unknown)~~
	~~!Notes~~
	\|-
	~~\|Multiple SNPs (e.g., FGFR2, MAP3K1, TOX3)~~
	~~\|Regulatory/epigenetic, not traditional oncogenes/TSGs~~
	~~\|Common, MAF >1%~~
	~~\|Varies~~
	~~\|Varies~~
	~~\|No~~
	~~\|Limited~~
	~~\|Yes (PRS applications~~
	~~\|Target gene expression changes may affect oncogenic pathways~~
	\|}
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

Jennelleh at 18:46, 22 June 2025

2025-06-22T18:46:23Z

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Jennelleh at 18:23, 22 June 2025

2025-06-22T18:23:15Z

← Older revision		Revision as of 13:23, 22 June 2025
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	[[~~GTS5~~:Table_of_Contents\|~~Genetic Tumour Syndromes~~ (~~Who~~ Classification, 5th ed.)]]		[[BRST5:Table_of_Contents\|Breast Tumours (WHO Classification, 5th ed.)]]
	{{Under Construction}}		{{Under Construction}}
	<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>		<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>

Jennelleh at 18:21, 22 June 2025

2025-06-22T18:21:47Z

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Lynn.Hu: /* Morphologic Features */

2025-06-22T15:25:11Z

Morphologic Features

← Older revision		Revision as of 10:25, 22 June 2025
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	\|}		\|}
	==Definition / Description of Disease==		==Definition / Description of Disease==
	The polygenic component of breast cancer refers to the combined effect of many common SNPs, each conferring a small increase in risk, typically under 1.3-fold. Identified mainly through GWAS, these low-penetrance variants collectively explain 18–20% of familial breast cancer risk and are quantified using a polygenic risk score (PRS) <ref>{{Cite journal\|last=Michailidou\|first=Kyriaki\|last2=Lindström\|first2=Sara\|last3=Dennis\|first3=Joe\|last4=Beesley\|first4=Jonathan\|last5=Hui\|first5=Shirley\|last6=Kar\|first6=Siddhartha\|last7=Lemaçon\|first7=Audrey\|last8=Soucy\|first8=Penny\|last9=Glubb\|first9=Dylan\|date=2017-11-02\|title=Association analysis identifies 65 new breast cancer risk loci\|url=https://pubmed.ncbi.nlm.nih.gov/29059683\|journal=Nature\|volume=551\|issue=7678\|pages=92–94\|doi=10.1038/nature24284\|issn=1476-4687\|pmc=5798588\|pmid=29059683}}</ref><ref>{{Cite journal\|last=Mavaddat\|first=Nasim\|last2=Pharoah\|first2=Paul D. P.\|last3=Michailidou\|first3=Kyriaki\|last4=Tyrer\|first4=Jonathan\|last5=Brook\|first5=Mark N.\|last6=Bolla\|first6=Manjeet K.\|last7=Wang\|first7=Qin\|last8=Dennis\|first8=Joe\|last9=Dunning\|first9=Alison M.\|date=2015-05\|title=Prediction of breast cancer risk based on profiling with common genetic variants\|url=https://pubmed.ncbi.nlm.nih.gov/25855707\|journal=Journal of the National Cancer Institute\|volume=107\|issue=5\|pages=djv036\|doi=10.1093/jnci/djv036\|issn=1460-2105\|pmc=4754625\|pmid=25855707}}</ref>.		The polygenic component of breast cancer refers to the combined effect of many common SNPs, each conferring a small increase in risk, typically under 1.3-fold. Identified mainly through GWAS, these low-penetrance variants collectively explain 18–20% of familial breast cancer risk and are quantified using a polygenic risk score (PRS) <ref name=":0">{{Cite journal\|last=Michailidou\|first=Kyriaki\|last2=Lindström\|first2=Sara\|last3=Dennis\|first3=Joe\|last4=Beesley\|first4=Jonathan\|last5=Hui\|first5=Shirley\|last6=Kar\|first6=Siddhartha\|last7=Lemaçon\|first7=Audrey\|last8=Soucy\|first8=Penny\|last9=Glubb\|first9=Dylan\|date=2017-11-02\|title=Association analysis identifies 65 new breast cancer risk loci\|url=https://pubmed.ncbi.nlm.nih.gov/29059683\|journal=Nature\|volume=551\|issue=7678\|pages=92–94\|doi=10.1038/nature24284\|issn=1476-4687\|pmc=5798588\|pmid=29059683}}</ref><ref name=":1">{{Cite journal\|last=Mavaddat\|first=Nasim\|last2=Pharoah\|first2=Paul D. P.\|last3=Michailidou\|first3=Kyriaki\|last4=Tyrer\|first4=Jonathan\|last5=Brook\|first5=Mark N.\|last6=Bolla\|first6=Manjeet K.\|last7=Wang\|first7=Qin\|last8=Dennis\|first8=Joe\|last9=Dunning\|first9=Alison M.\|date=2015-05\|title=Prediction of breast cancer risk based on profiling with common genetic variants\|url=https://pubmed.ncbi.nlm.nih.gov/25855707\|journal=Journal of the National Cancer Institute\|volume=107\|issue=5\|pages=djv036\|doi=10.1093/jnci/djv036\|issn=1460-2105\|pmc=4754625\|pmid=25855707}}</ref>.
	==Synonyms / Terminology==		==Synonyms / Terminology==
	Polygenic breast cancer risk; Common low-penetrance breast cancer alleles		Polygenic breast cancer risk; Common low-penetrance breast cancer alleles
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	Breast tissue (parenchyma)		Breast tissue (parenchyma)
	==Morphologic Features==		==Morphologic Features==
	~~Put your text here~~ <~~span style~~="~~color~~:~~#0070C0~~">~~(''Instructions~~: ~~Brief description of typically approximately one paragraph'')~~ </~~span~~>		There are no specific histologic features directly attributable to polygenic risk alleles. However, these variants tend to be enriched in specific breast cancer subtypes. For example, ER-positive tumors, which are estrogen receptor–driven and often of ductal histology, are more strongly associated with many common susceptibility alleles. In contrast, ER-negative tumors, including those seen more frequently in BRCA1 mutation carriers, show enrichment for a smaller subset of variants. Similarly, lobular carcinomas—characterized by a lack of E-cadherin expression—have been associated with unique risk variants distinct from those found in ductal carcinomas<ref name=":2">{{Cite journal\|last=Sawyer\|first=Elinor\|last2=Roylance\|first2=Rebecca\|last3=Petridis\|first3=Christos\|last4=Brook\|first4=Mark N.\|last5=Nowinski\|first5=Salpie\|last6=Papouli\|first6=Efterpi\|last7=Fletcher\|first7=Olivia\|last8=Pinder\|first8=Sarah\|last9=Hanby\|first9=Andrew\|date=2014-04\|title=Genetic predisposition to in situ and invasive lobular carcinoma of the breast\|url=https://pubmed.ncbi.nlm.nih.gov/24743323\|journal=PLoS genetics\|volume=10\|issue=4\|pages=e1004285\|doi=10.1371/journal.pgen.1004285\|issn=1553-7404\|pmc=3990493\|pmid=24743323}}</ref>.
	==Immunophenotype==		==Immunophenotype==
	N/A		N/A
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	\|}		\|}
	==Gene Mutations (SNV / INDEL)==		==Gene Mutations (SNV / INDEL)==
	~~Put your text here and fill~~ in ~~the table~~ <~~span style~~="~~color~~:~~#0070C0~~">(~~''Instructions~~: ~~This table is not meant to be an exhaustive list; please include only genes~~/~~alterations that are recurrent and common as well either disease defining and~~/~~or clinically significant~~. ~~Can include references in~~ the ~~table~~. ~~For clinical significance, denote associations with FDA~~-~~approved therapy (not an extensive list~~ of ~~applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews~~ of ~~gene mutations~~ in ~~this entity~~. ~~Do not delete table~~.~~'')~~ </~~span~~>		SNPs in FGFR2 are more common in ER-positive ductal carcinoma; variants in 7q34 are associated with lobular carcinoma; ER-negative cancers (e.g., seen in BRCA1 carriers) are linked to 19p13.1 variants<ref name=":2" /><ref>{{Cite journal\|last=Mavaddat\|first=Nasim\|last2=Barrowdale\|first2=Daniel\|last3=Andrulis\|first3=Irene L.\|last4=Domchek\|first4=Susan M.\|last5=Eccles\|first5=Diana\|last6=Nevanlinna\|first6=Heli\|last7=Ramus\|first7=Susan J.\|last8=Spurdle\|first8=Amanda\|last9=Robson\|first9=Mark\|date=2012-01\|title=Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)\|url=https://pubmed.ncbi.nlm.nih.gov/22144499\|journal=Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology\|volume=21\|issue=1\|pages=134–147\|doi=10.1158/1055-9965.EPI-11-0775\|issn=1538-7755\|pmc=3272407\|pmid=22144499}}</ref><ref>{{Cite journal\|last=Kuchenbaecker\|first=Karoline B.\|last2=Neuhausen\|first2=Susan L.\|last3=Robson\|first3=Mark\|last4=Barrowdale\|first4=Daniel\|last5=McGuffog\|first5=Lesley\|last6=Mulligan\|first6=Anna Marie\|last7=Andrulis\|first7=Irene L.\|last8=Spurdle\|first8=Amanda B.\|last9=Schmidt\|first9=Marjanka K.\|date=2014-12-31\|title=Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers\|url=https://pubmed.ncbi.nlm.nih.gov/25919761\|journal=Breast cancer research: BCR\|volume=16\|issue=6\|pages=3416\|doi=10.1186/s13058-014-0492-9\|issn=1465-542X\|pmc=4406179\|pmid=25919761}}</ref>.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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	\|}Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.		\|}Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
	==Epigenomic Alterations==		==Epigenomic Alterations==
	Common variants are often located in enhancer regions, affecting chromatin accessibility, transcription factor binding, and gene expression regulation (e.g., at ESR1, FGFR2, MAP3K1 loci).		Common variants are often located in enhancer regions, affecting chromatin accessibility, transcription factor binding, and gene expression regulation (e.g., at ESR1, FGFR2, MAP3K1 loci) <ref>{{Cite journal\|last=Rivandi\|first=Mahdi\|last2=Martens\|first2=John W. M.\|last3=Hollestelle\|first3=Antoinette\|date=2018\|title=Elucidating the Underlying Functional Mechanisms of Breast Cancer Susceptibility Through Post-GWAS Analyses\|url=https://pubmed.ncbi.nlm.nih.gov/30116257\|journal=Frontiers in Genetics\|volume=9\|pages=280\|doi=10.3389/fgene.2018.00280\|issn=1664-8021\|pmc=6082943\|pmid=30116257}}</ref><ref name=":0" />.
	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==
	<br />		<br />
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==
	Polygenic risk is assessed through genotyping panels or whole-genome SNP arrays followed by computational calculation of the PRS.		Polygenic risk is assessed through genotyping panels or whole-genome SNP arrays followed by computational calculation of the PRS<ref>{{Cite journal\|last=Sawyer\|first=Sarah\|last2=Mitchell\|first2=Gillian\|last3=McKinley\|first3=Joanne\|last4=Chenevix-Trench\|first4=Georgia\|last5=Beesley\|first5=Jonathan\|last6=Chen\|first6=Xiao Qing\|last7=Bowtell\|first7=David\|last8=Trainer\|first8=Alison H.\|last9=Harris\|first9=Marion\|date=2012-12-10\|title=A role for common genomic variants in the assessment of familial breast cancer\|url=https://pubmed.ncbi.nlm.nih.gov/23109704\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=30\|issue=35\|pages=4330–4336\|doi=10.1200/JCO.2012.41.7469\|issn=1527-7755\|pmid=23109704}}</ref><ref>{{Cite journal\|last=Dite\|first=Gillian S.\|last2=MacInnis\|first2=Robert J.\|last3=Bickerstaffe\|first3=Adrian\|last4=Dowty\|first4=James G.\|last5=Allman\|first5=Richard\|last6=Apicella\|first6=Carmel\|last7=Milne\|first7=Roger L.\|last8=Tsimiklis\|first8=Helen\|last9=Phillips\|first9=Kelly-Anne\|date=2016-02\|title=Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk-Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry\|url=https://pubmed.ncbi.nlm.nih.gov/26677205\|journal=Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology\|volume=25\|issue=2\|pages=359–365\|doi=10.1158/1055-9965.EPI-15-0838\|issn=1538-7755\|pmc=4767544\|pmid=26677205}}</ref><ref name=":1" />.
	==Familial Forms==		==Familial Forms==
	These low-penetrance alleles can act additively or multiplicatively with rare high-penetrance pathogenic variants (e.g., BRCA1, BRCA2) and may modify cancer risk within families with hereditary breast and ovarian cancer syndromes.		These low-penetrance alleles can act additively or multiplicatively with rare high-penetrance pathogenic variants (e.g., BRCA1, BRCA2) and may modify cancer risk within families with hereditary breast and ovarian cancer syndromes<ref>{{Cite journal\|last=Kuchenbaecker\|first=Karoline B.\|last2=McGuffog\|first2=Lesley\|last3=Barrowdale\|first3=Daniel\|last4=Lee\|first4=Andrew\|last5=Soucy\|first5=Penny\|last6=Dennis\|first6=Joe\|last7=Domchek\|first7=Susan M.\|last8=Robson\|first8=Mark\|last9=Spurdle\|first9=Amanda B.\|date=2017-07-01\|title=Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers\|url=https://pubmed.ncbi.nlm.nih.gov/28376175\|journal=Journal of the National Cancer Institute\|volume=109\|issue=7\|pages=djw302\|doi=10.1093/jnci/djw302\|issn=1460-2105\|pmc=5408990\|pmid=28376175}}</ref>.
	==Additional Information==		==Additional Information==
	The utility of PRS in clinical practice is growing, both for general population risk stratification and for risk modification in individuals with known pathogenic variants in high-risk genes.		The utility of PRS in clinical practice is growing, both for general population risk stratification and for risk modification in individuals with known pathogenic variants in high-risk genes<ref>{{Cite journal\|last=Kuchenbaecker\|first=Karoline B.\|last2=McGuffog\|first2=Lesley\|last3=Barrowdale\|first3=Daniel\|last4=Lee\|first4=Andrew\|last5=Soucy\|first5=Penny\|last6=Dennis\|first6=Joe\|last7=Domchek\|first7=Susan M.\|last8=Robson\|first8=Mark\|last9=Spurdle\|first9=Amanda B.\|date=2017-07-01\|title=Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers\|url=https://pubmed.ncbi.nlm.nih.gov/28376175\|journal=Journal of the National Cancer Institute\|volume=109\|issue=7\|pages=djw302\|doi=10.1093/jnci/djw302\|issn=1460-2105\|pmc=5408990\|pmid=28376175}}</ref>.
	==Links==		==Links==
	(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>		(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
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	==Notes==		==Notes==
	<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.		<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
			<references />

Lynn.Hu: /* Primary Author(s)* */

2025-06-22T14:52:36Z

Primary Author(s)*

← Older revision		Revision as of 09:52, 22 June 2025
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	<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>		<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
	==Primary Author(s)*==		==Primary Author(s)*==
	Xiaolin Hu		Xiaolin Hu, GeneDx
	==WHO Classification of Disease==		==WHO Classification of Disease==
	<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span>		<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span>
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	==Definition / Description of Disease==		==Definition / Description of Disease==
	The polygenic component of breast cancer refers to the combined effect of many common SNPs, each conferring a small increase in risk, typically under 1.3-fold. Identified mainly through GWAS, these low-penetrance variants collectively explain 18–20% of familial breast cancer risk and are quantified using a polygenic risk score (PRS).		The polygenic component of breast cancer refers to the combined effect of many common SNPs, each conferring a small increase in risk, typically under 1.3-fold. Identified mainly through GWAS, these low-penetrance variants collectively explain 18–20% of familial breast cancer risk and are quantified using a polygenic risk score (PRS) <ref>{{Cite journal\|last=Michailidou\|first=Kyriaki\|last2=Lindström\|first2=Sara\|last3=Dennis\|first3=Joe\|last4=Beesley\|first4=Jonathan\|last5=Hui\|first5=Shirley\|last6=Kar\|first6=Siddhartha\|last7=Lemaçon\|first7=Audrey\|last8=Soucy\|first8=Penny\|last9=Glubb\|first9=Dylan\|date=2017-11-02\|title=Association analysis identifies 65 new breast cancer risk loci\|url=https://pubmed.ncbi.nlm.nih.gov/29059683\|journal=Nature\|volume=551\|issue=7678\|pages=92–94\|doi=10.1038/nature24284\|issn=1476-4687\|pmc=5798588\|pmid=29059683}}</ref><ref>{{Cite journal\|last=Mavaddat\|first=Nasim\|last2=Pharoah\|first2=Paul D. P.\|last3=Michailidou\|first3=Kyriaki\|last4=Tyrer\|first4=Jonathan\|last5=Brook\|first5=Mark N.\|last6=Bolla\|first6=Manjeet K.\|last7=Wang\|first7=Qin\|last8=Dennis\|first8=Joe\|last9=Dunning\|first9=Alison M.\|date=2015-05\|title=Prediction of breast cancer risk based on profiling with common genetic variants\|url=https://pubmed.ncbi.nlm.nih.gov/25855707\|journal=Journal of the National Cancer Institute\|volume=107\|issue=5\|pages=djv036\|doi=10.1093/jnci/djv036\|issn=1460-2105\|pmc=4754625\|pmid=25855707}}</ref>.
	==Synonyms / Terminology==		==Synonyms / Terminology==
	Polygenic breast cancer risk; Common low-penetrance breast cancer alleles		Polygenic breast cancer risk; Common low-penetrance breast cancer alleles
	==Epidemiology / Prevalence==		==Epidemiology / Prevalence==
	Over 170 low-penetrance alleles have been identified, primarily in populations of European descent, accounting for approximately 18% of familial breast cancer risk. These loci are found in the general population with varying allele frequencies and are being increasingly incorporated into risk prediction models.		Over 170 low-penetrance alleles have been identified, primarily in populations of European descent, accounting for approximately 18% of familial breast cancer risk<ref>{{Cite journal\|last=Adam\|first=Kevin\|last2=Hunter\|first2=Tony\|date=2018-02\|title=Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes\|url=https://pubmed.ncbi.nlm.nih.gov/29058706\|journal=Laboratory Investigation; a Journal of Technical Methods and Pathology\|volume=98\|issue=2\|pages=233–247\|doi=10.1038/labinvest.2017.118\|issn=1530-0307\|pmc=5815933\|pmid=29058706}}</ref>. These loci are found in the general population with varying allele frequencies and are being increasingly incorporated into risk prediction models.
	==Clinical Features==		==Clinical Features==
	<br />		<br />

Lynn.Hu: /* Definition / Description of Disease */

2025-06-22T14:35:41Z

Definition / Description of Disease

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