Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

Anna Nurmi, Taru A. Muranen, Liisa M. Pelttari, Johanna I. Kiiski, Tuomas Heikkinen, Sini Lehto, Anne Kallioniemi, Johanna Schleutker, Ralf Bützow, Carl Blomqvist, Kristiina Aittomäki, Heli Nevanlinna

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C, and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3156 cases and 2089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish breast cancer patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of breast cancer in the unselected patient group (OR=5.40 [95% CI 1.58-18.45], p=0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2487 breast cancer patients, 556 ovarian cancer patients, and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1141 BRCA1/2-negative familial breast cancer patients, 7.5% in 1727 unselected breast cancer patients, and 7.2% in 556 unselected ovarian cancer patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR=2.63 [1.15-5.48], p=0.011]. These results support gene panel testing of even multiple members of breast cancer families where several mutations may segregate in different individuals. This article is protected by copyright. All rights reserved.
Alkuperäiskielienglanti
LehtiInternational Journal of Cancer
ISSN0020-7136
DOI - pysyväislinkit
TilaJulkaistu - 30 maaliskuuta 2019
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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@article{8311b4d1963e41e29ec7598c48c3f05a,
title = "Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients",
abstract = "Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C, and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3156 cases and 2089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish breast cancer patients. CHEK2 c.319+2T>A was detected in 0.7{\%} of the patients, and it was associated with a high risk of breast cancer in the unselected patient group (OR=5.40 [95{\%} CI 1.58-18.45], p=0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1{\%} of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2487 breast cancer patients, 556 ovarian cancer patients, and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3{\%} in 1141 BRCA1/2-negative familial breast cancer patients, 7.5{\%} in 1727 unselected breast cancer patients, and 7.2{\%} in 556 unselected ovarian cancer patients. At least one moderate-risk gene mutation was found in 12.5{\%} of BRCA1 families and 7.1{\%} of BRCA1 index patients, as well as in 17.0{\%} of BRCA2 families and 11.3{\%} of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR=2.63 [1.15-5.48], p=0.011]. These results support gene panel testing of even multiple members of breast cancer families where several mutations may segregate in different individuals. This article is protected by copyright. All rights reserved.",
keywords = "breast cancer, ovarian cancer, moderate-risk gene, double heterozygote, CHEK2, 3122 Cancers",
author = "Anna Nurmi and Muranen, {Taru A.} and Pelttari, {Liisa M.} and Kiiski, {Johanna I.} and Tuomas Heikkinen and Sini Lehto and Anne Kallioniemi and Johanna Schleutker and Ralf B{\"u}tzow and Carl Blomqvist and Kristiina Aittom{\"a}ki and Heli Nevanlinna",
year = "2019",
month = "3",
day = "30",
doi = "10.1002/ijc.32309",
language = "English",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley",

}

Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients. / Nurmi, Anna; Muranen, Taru A.; Pelttari, Liisa M.; Kiiski, Johanna I.; Heikkinen, Tuomas; Lehto, Sini; Kallioniemi, Anne; Schleutker, Johanna; Bützow, Ralf; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli.

julkaisussa: International Journal of Cancer, 30.03.2019.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

AU - Nurmi, Anna

AU - Muranen, Taru A.

AU - Pelttari, Liisa M.

AU - Kiiski, Johanna I.

AU - Heikkinen, Tuomas

AU - Lehto, Sini

AU - Kallioniemi, Anne

AU - Schleutker, Johanna

AU - Bützow, Ralf

AU - Blomqvist, Carl

AU - Aittomäki, Kristiina

AU - Nevanlinna, Heli

PY - 2019/3/30

Y1 - 2019/3/30

N2 - Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C, and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3156 cases and 2089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish breast cancer patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of breast cancer in the unselected patient group (OR=5.40 [95% CI 1.58-18.45], p=0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2487 breast cancer patients, 556 ovarian cancer patients, and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1141 BRCA1/2-negative familial breast cancer patients, 7.5% in 1727 unselected breast cancer patients, and 7.2% in 556 unselected ovarian cancer patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR=2.63 [1.15-5.48], p=0.011]. These results support gene panel testing of even multiple members of breast cancer families where several mutations may segregate in different individuals. This article is protected by copyright. All rights reserved.

AB - Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C, and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3156 cases and 2089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish breast cancer patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of breast cancer in the unselected patient group (OR=5.40 [95% CI 1.58-18.45], p=0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2487 breast cancer patients, 556 ovarian cancer patients, and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1141 BRCA1/2-negative familial breast cancer patients, 7.5% in 1727 unselected breast cancer patients, and 7.2% in 556 unselected ovarian cancer patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR=2.63 [1.15-5.48], p=0.011]. These results support gene panel testing of even multiple members of breast cancer families where several mutations may segregate in different individuals. This article is protected by copyright. All rights reserved.

KW - breast cancer

KW - ovarian cancer

KW - moderate-risk gene

KW - double heterozygote

KW - CHEK2

KW - 3122 Cancers

U2 - 10.1002/ijc.32309

DO - 10.1002/ijc.32309

M3 - Article

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

ER -