Is RNASEL

P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

Tú Nguyen-Dumont, Zhi L. Teo, Fleur Hammet, Alexis Roberge, Maryam Mahmoodi, Helen Tsimiklis, Daniel J. Park, Bernard J. Pope, Andrew Lonie, Miroslav K. Kapuscinski, Khalid Mahmood, ABCFR, David E. Goldgar, Graham G. Giles, Ingrid Winship, John L. Hopper, Melissa C. Southey

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Background: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. Methods: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. Results: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p<0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Conclusion: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

Original languageEnglish
Article number165
Number of pages7
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 8 Feb 2018

Keywords

  • Breast cancer
  • Early-onset cancer
  • Modifier risk gene
  • RNASEL:P.Glu265

Cite this

Nguyen-Dumont, Tú ; Teo, Zhi L. ; Hammet, Fleur ; Roberge, Alexis ; Mahmoodi, Maryam ; Tsimiklis, Helen ; Park, Daniel J. ; Pope, Bernard J. ; Lonie, Andrew ; Kapuscinski, Miroslav K. ; Mahmood, Khalid ; ABCFR ; Goldgar, David E. ; Giles, Graham G. ; Winship, Ingrid ; Hopper, John L. ; Southey, Melissa C. / Is RNASEL : P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
@article{347377682d74452eb27948d089a6b889,
title = "Is RNASEL: P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?",
abstract = "Background: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. Methods: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. Results: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60{\%}) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5{\%}) (p<0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Conclusion: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.",
keywords = "Breast cancer, Early-onset cancer, Modifier risk gene, RNASEL:P.Glu265",
author = "T{\'u} Nguyen-Dumont and Teo, {Zhi L.} and Fleur Hammet and Alexis Roberge and Maryam Mahmoodi and Helen Tsimiklis and Park, {Daniel J.} and Pope, {Bernard J.} and Andrew Lonie and Kapuscinski, {Miroslav K.} and Khalid Mahmood and ABCFR and Goldgar, {David E.} and Giles, {Graham G.} and Ingrid Winship and Hopper, {John L.} and Southey, {Melissa C.}",
year = "2018",
month = "2",
day = "8",
doi = "10.1186/s12885-018-4028-z",
language = "English",
volume = "18",
journal = "BMC Cancer",
issn = "1471-2407",
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Nguyen-Dumont, T, Teo, ZL, Hammet, F, Roberge, A, Mahmoodi, M, Tsimiklis, H, Park, DJ, Pope, BJ, Lonie, A, Kapuscinski, MK, Mahmood, K, ABCFR, Goldgar, DE, Giles, GG, Winship, I, Hopper, JL & Southey, MC 2018, 'Is RNASEL: P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?', BMC Cancer, vol. 18, no. 1, 165. https://doi.org/10.1186/s12885-018-4028-z

Is RNASEL : P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations? / Nguyen-Dumont, Tú; Teo, Zhi L.; Hammet, Fleur; Roberge, Alexis; Mahmoodi, Maryam; Tsimiklis, Helen; Park, Daniel J.; Pope, Bernard J.; Lonie, Andrew; Kapuscinski, Miroslav K.; Mahmood, Khalid; ABCFR; Goldgar, David E.; Giles, Graham G.; Winship, Ingrid; Hopper, John L.; Southey, Melissa C.

In: BMC Cancer, Vol. 18, No. 1, 165, 08.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Is RNASEL

T2 - P.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

AU - Nguyen-Dumont, Tú

AU - Teo, Zhi L.

AU - Hammet, Fleur

AU - Roberge, Alexis

AU - Mahmoodi, Maryam

AU - Tsimiklis, Helen

AU - Park, Daniel J.

AU - Pope, Bernard J.

AU - Lonie, Andrew

AU - Kapuscinski, Miroslav K.

AU - Mahmood, Khalid

AU - ABCFR

AU - Goldgar, David E.

AU - Giles, Graham G.

AU - Winship, Ingrid

AU - Hopper, John L.

AU - Southey, Melissa C.

PY - 2018/2/8

Y1 - 2018/2/8

N2 - Background: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. Methods: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. Results: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p<0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Conclusion: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

AB - Background: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. Methods: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. Results: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p<0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Conclusion: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

KW - Breast cancer

KW - Early-onset cancer

KW - Modifier risk gene

KW - RNASEL:P.Glu265

UR - http://www.scopus.com/inward/record.url?scp=85041826222&partnerID=8YFLogxK

U2 - 10.1186/s12885-018-4028-z

DO - 10.1186/s12885-018-4028-z

M3 - Article

VL - 18

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 165

ER -