ERCC3, a new ovarian cancer susceptibility gene?
Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited disorder with an increased risk of breast cancer (BC) and ovarian cancers (OC). Mutations in BRCA1-BRCA2 explains less than a half of cases. In the last decade several genes with different penetrance have been associated with an in...
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| Veröffentlicht in: | European journal of cancer (1990) 2020-12, Vol.141, p.1-8 |
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| creator | Stradella, Agostina del Valle, Jesús Rofes, Paula Vargas-Parra, Gardenia Salinas, Mónica González, Sara Montes, Eva López-Doriga, Adriana Gómez, Carolina de Cid, Rafael Darder, Esther Teulé, Alex Solanes, Ares Munté, Elisabet Capellà, Gabriel Pineda, Marta Feliubadaló, Lidia Brunet, Joan Lázaro, Conxi |
| description | Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited disorder with an increased risk of breast cancer (BC) and ovarian cancers (OC). Mutations in BRCA1-BRCA2 explains less than a half of cases. In the last decade several genes with different penetrance have been associated with an increased risk of BC or OC. A recurrent heterozygous ERCC3 truncating mutation increases the risk for breast cancer in patients with Ashkenazi Jewish ancestry. Our study aimed to investigate the role of ERCC3 truncating variants in a cohort of patients with suspicion of HBOC.
ERCC3 screening by multigene-panel analysis in 1311 unrelated patients after our regional consensus for genetic testing in hereditary cancer was done. In addition, 453 Spanish cancer-free individuals and 51,343 GnomAD non-Finnish, non-cancer European individuals were used as control populations.
We identified 13 patients with heterozygous ERCC3 truncating variants (0.99%). Five of them also carried a mutation in a high- /moderate-penetrance HBOC gene (BRCA1, BRCA2, CHEK2, and TP53) being Multilocus Inherited Neoplasia Alleles syndrome (MINAS) patients. The frequency in 453 Spanish controls was of 0.22%; similar to that observed in 51,343 non-Finnish European GnomAD population (0.24%). We found an almost statistically significant association of truncating ERCC3 variants with BC (odds ratio [OR] = 2.25, confidence interval [CI] = 0.6–5.93, P = 0.11), and we observed for the first time a significant association with OC (OR = 4.74, CI = 1–14.34, P = 0.028), that holds even after removing MINAS cases.
To our knowledge, this is the largest HBOC series comprehensively analysed for ERCC3 mutations, and the first study identifying ERCC3 as a cancer risk for OC.
•Our results confirm the association of ERCC3 truncating mutations with breast cancer.•We also describe their association with ovarian cancer for the first time. Further studies in larger cohorts are needed to more precisely establish the associated cancer risk as well as the relation with other cancer types. |
| doi_str_mv | 10.1016/j.ejca.2020.09.023 |
| format | Article |
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ERCC3 screening by multigene-panel analysis in 1311 unrelated patients after our regional consensus for genetic testing in hereditary cancer was done. In addition, 453 Spanish cancer-free individuals and 51,343 GnomAD non-Finnish, non-cancer European individuals were used as control populations.
We identified 13 patients with heterozygous ERCC3 truncating variants (0.99%). Five of them also carried a mutation in a high- /moderate-penetrance HBOC gene (BRCA1, BRCA2, CHEK2, and TP53) being Multilocus Inherited Neoplasia Alleles syndrome (MINAS) patients. The frequency in 453 Spanish controls was of 0.22%; similar to that observed in 51,343 non-Finnish European GnomAD population (0.24%). We found an almost statistically significant association of truncating ERCC3 variants with BC (odds ratio [OR] = 2.25, confidence interval [CI] = 0.6–5.93, P = 0.11), and we observed for the first time a significant association with OC (OR = 4.74, CI = 1–14.34, P = 0.028), that holds even after removing MINAS cases.
To our knowledge, this is the largest HBOC series comprehensively analysed for ERCC3 mutations, and the first study identifying ERCC3 as a cancer risk for OC.
•Our results confirm the association of ERCC3 truncating mutations with breast cancer.•We also describe their association with ovarian cancer for the first time. Further studies in larger cohorts are needed to more precisely establish the associated cancer risk as well as the relation with other cancer types.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2020.09.023</identifier><identifier>PMID: 33125943</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; BRCA1 protein ; BRCA2 protein ; Breast cancer ; Confidence intervals ; DNA Helicases - genetics ; DNA-Binding Proteins - genetics ; ERCC3 ; Female ; Genetic disorders ; Genetic Predisposition to Disease - genetics ; Genetic screening ; HBOC ; Health risks ; Hereditary Breast and Ovarian Cancer ; Hereditary Breast and Ovarian Cancer Syndrome - genetics ; Humans ; Middle Aged ; Moderate cancer risk ; Mutation ; Ovarian cancer ; p53 Protein ; Pedigree ; Population control ; Risk ; Statistical analysis</subject><ispartof>European journal of cancer (1990), 2020-12, Vol.141, p.1-8</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Dec 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-3cc4b866cc0f59ce84d9f925051db081839197343719e1a0ecdcb9db7a965b913</citedby><cites>FETCH-LOGICAL-c384t-3cc4b866cc0f59ce84d9f925051db081839197343719e1a0ecdcb9db7a965b913</cites><orcidid>0000-0003-1945-3512 ; 0000-0002-7764-1397 ; 0000-0002-2307-8869 ; 0000-0003-1378-736X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0959804920310327$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33125943$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stradella, Agostina</creatorcontrib><creatorcontrib>del Valle, Jesús</creatorcontrib><creatorcontrib>Rofes, Paula</creatorcontrib><creatorcontrib>Vargas-Parra, Gardenia</creatorcontrib><creatorcontrib>Salinas, Mónica</creatorcontrib><creatorcontrib>González, Sara</creatorcontrib><creatorcontrib>Montes, Eva</creatorcontrib><creatorcontrib>López-Doriga, Adriana</creatorcontrib><creatorcontrib>Gómez, Carolina</creatorcontrib><creatorcontrib>de Cid, Rafael</creatorcontrib><creatorcontrib>Darder, Esther</creatorcontrib><creatorcontrib>Teulé, Alex</creatorcontrib><creatorcontrib>Solanes, Ares</creatorcontrib><creatorcontrib>Munté, Elisabet</creatorcontrib><creatorcontrib>Capellà, Gabriel</creatorcontrib><creatorcontrib>Pineda, Marta</creatorcontrib><creatorcontrib>Feliubadaló, Lidia</creatorcontrib><creatorcontrib>Brunet, Joan</creatorcontrib><creatorcontrib>Lázaro, Conxi</creatorcontrib><title>ERCC3, a new ovarian cancer susceptibility gene?</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited disorder with an increased risk of breast cancer (BC) and ovarian cancers (OC). Mutations in BRCA1-BRCA2 explains less than a half of cases. In the last decade several genes with different penetrance have been associated with an increased risk of BC or OC. A recurrent heterozygous ERCC3 truncating mutation increases the risk for breast cancer in patients with Ashkenazi Jewish ancestry. Our study aimed to investigate the role of ERCC3 truncating variants in a cohort of patients with suspicion of HBOC.
ERCC3 screening by multigene-panel analysis in 1311 unrelated patients after our regional consensus for genetic testing in hereditary cancer was done. In addition, 453 Spanish cancer-free individuals and 51,343 GnomAD non-Finnish, non-cancer European individuals were used as control populations.
We identified 13 patients with heterozygous ERCC3 truncating variants (0.99%). Five of them also carried a mutation in a high- /moderate-penetrance HBOC gene (BRCA1, BRCA2, CHEK2, and TP53) being Multilocus Inherited Neoplasia Alleles syndrome (MINAS) patients. The frequency in 453 Spanish controls was of 0.22%; similar to that observed in 51,343 non-Finnish European GnomAD population (0.24%). We found an almost statistically significant association of truncating ERCC3 variants with BC (odds ratio [OR] = 2.25, confidence interval [CI] = 0.6–5.93, P = 0.11), and we observed for the first time a significant association with OC (OR = 4.74, CI = 1–14.34, P = 0.028), that holds even after removing MINAS cases.
To our knowledge, this is the largest HBOC series comprehensively analysed for ERCC3 mutations, and the first study identifying ERCC3 as a cancer risk for OC.
•Our results confirm the association of ERCC3 truncating mutations with breast cancer.•We also describe their association with ovarian cancer for the first time. Further studies in larger cohorts are needed to more precisely establish the associated cancer risk as well as the relation with other cancer types.</description><subject>Adult</subject><subject>BRCA1 protein</subject><subject>BRCA2 protein</subject><subject>Breast cancer</subject><subject>Confidence intervals</subject><subject>DNA Helicases - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>ERCC3</subject><subject>Female</subject><subject>Genetic disorders</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic screening</subject><subject>HBOC</subject><subject>Health risks</subject><subject>Hereditary Breast and Ovarian Cancer</subject><subject>Hereditary Breast and Ovarian Cancer Syndrome - genetics</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Moderate cancer risk</subject><subject>Mutation</subject><subject>Ovarian cancer</subject><subject>p53 Protein</subject><subject>Pedigree</subject><subject>Population control</subject><subject>Risk</subject><subject>Statistical analysis</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVJabbb_oEeiiGXHmp3xpItDQRCWNIPCBRCehayPFtkdu2NZKfk31fLpj300NNcnvflnUeIdwgVArafhooH76oaaqiAKqjlC7FCo6kE09RnYgXUUGlA0bl4ndIAANooeCXOpcS6ISVXAm7uNhv5sXDFyL-K6dHF4MbCu9FzLNKSPB_m0IVdmJ-Knzzy1Rvxcut2id8-37X48fnmfvO1vP3-5dvm-rb00qi5lN6rzrSt97BtyLNRPW2pbqDBvgODRhKSlkpqJEYH7HvfUd9pR23TEcq1-HDqPcTpYeE0233Ia3Y7N_K0JFurplWIlL9ei4t_0GFa4pjXZUprjahRZ6o-UT5OKUXe2kMMexefLII9-rSDPfq0R58WyObmHHr_XL10e-7_Rv4IzMDlCeDs4jFwtMkHzvb6ENnPtp_C__p_A8i-gwY</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Stradella, Agostina</creator><creator>del Valle, Jesús</creator><creator>Rofes, Paula</creator><creator>Vargas-Parra, Gardenia</creator><creator>Salinas, Mónica</creator><creator>González, Sara</creator><creator>Montes, Eva</creator><creator>López-Doriga, Adriana</creator><creator>Gómez, Carolina</creator><creator>de Cid, Rafael</creator><creator>Darder, Esther</creator><creator>Teulé, Alex</creator><creator>Solanes, Ares</creator><creator>Munté, Elisabet</creator><creator>Capellà, Gabriel</creator><creator>Pineda, Marta</creator><creator>Feliubadaló, Lidia</creator><creator>Brunet, Joan</creator><creator>Lázaro, Conxi</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1945-3512</orcidid><orcidid>https://orcid.org/0000-0002-7764-1397</orcidid><orcidid>https://orcid.org/0000-0002-2307-8869</orcidid><orcidid>https://orcid.org/0000-0003-1378-736X</orcidid></search><sort><creationdate>202012</creationdate><title>ERCC3, a new ovarian cancer susceptibility gene?</title><author>Stradella, Agostina ; 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Mutations in BRCA1-BRCA2 explains less than a half of cases. In the last decade several genes with different penetrance have been associated with an increased risk of BC or OC. A recurrent heterozygous ERCC3 truncating mutation increases the risk for breast cancer in patients with Ashkenazi Jewish ancestry. Our study aimed to investigate the role of ERCC3 truncating variants in a cohort of patients with suspicion of HBOC.
ERCC3 screening by multigene-panel analysis in 1311 unrelated patients after our regional consensus for genetic testing in hereditary cancer was done. In addition, 453 Spanish cancer-free individuals and 51,343 GnomAD non-Finnish, non-cancer European individuals were used as control populations.
We identified 13 patients with heterozygous ERCC3 truncating variants (0.99%). Five of them also carried a mutation in a high- /moderate-penetrance HBOC gene (BRCA1, BRCA2, CHEK2, and TP53) being Multilocus Inherited Neoplasia Alleles syndrome (MINAS) patients. The frequency in 453 Spanish controls was of 0.22%; similar to that observed in 51,343 non-Finnish European GnomAD population (0.24%). We found an almost statistically significant association of truncating ERCC3 variants with BC (odds ratio [OR] = 2.25, confidence interval [CI] = 0.6–5.93, P = 0.11), and we observed for the first time a significant association with OC (OR = 4.74, CI = 1–14.34, P = 0.028), that holds even after removing MINAS cases.
To our knowledge, this is the largest HBOC series comprehensively analysed for ERCC3 mutations, and the first study identifying ERCC3 as a cancer risk for OC.
•Our results confirm the association of ERCC3 truncating mutations with breast cancer.•We also describe their association with ovarian cancer for the first time. Further studies in larger cohorts are needed to more precisely establish the associated cancer risk as well as the relation with other cancer types.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33125943</pmid><doi>10.1016/j.ejca.2020.09.023</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1945-3512</orcidid><orcidid>https://orcid.org/0000-0002-7764-1397</orcidid><orcidid>https://orcid.org/0000-0002-2307-8869</orcidid><orcidid>https://orcid.org/0000-0003-1378-736X</orcidid></addata></record> |
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| ispartof | European journal of cancer (1990), 2020-12, Vol.141, p.1-8 |
| issn | 0959-8049 1879-0852 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult BRCA1 protein BRCA2 protein Breast cancer Confidence intervals DNA Helicases - genetics DNA-Binding Proteins - genetics ERCC3 Female Genetic disorders Genetic Predisposition to Disease - genetics Genetic screening HBOC Health risks Hereditary Breast and Ovarian Cancer Hereditary Breast and Ovarian Cancer Syndrome - genetics Humans Middle Aged Moderate cancer risk Mutation Ovarian cancer p53 Protein Pedigree Population control Risk Statistical analysis |
| title | ERCC3, a new ovarian cancer susceptibility gene? |
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