Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers

Brian S. Finkelman, Wendy S. Rubinstein, Sue Friedman, Tara M. Friebel, Shera Dubitsky, Niecee Singer Schonberger, Rochelle Shoretz, Christian F. Singer, Joanne L. Blum, Nadine Tung, Olufunmilayo I. Olopade, Jeffrey N. Weitzel, Henry T. Lynch, Carrie Snyder, Judy E. Garber, Joellen Schildkraut, Mary B. Daly, Claudine Isaacs, Gabrielle Pichert, Susan L. Neuhausen & 11 others Fergus J. Couch, Laura Van't Veer, Rosalind Eeles, Elizabeth Bancroft, D. Gareth Evans, Patricia A. Ganz, Gail E. Tomlinson, Steven A. Narod, Ellen Matloff, Susan Domchek, Timothy R. Rebbeck

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

Original languageEnglish
Pages (from-to)1321-1328
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number12
DOIs
StatePublished - Apr 20 2012

Fingerprint

Risk Reduction Behavior
Ovarian Neoplasms
Breast Neoplasms
Mutation
Ovariectomy
Jews
Neoplasms
Proportional Hazards Models
Cohort Studies
Odds Ratio
Observation

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Finkelman, B. S., Rubinstein, W. S., Friedman, S., Friebel, T. M., Dubitsky, S., Schonberger, N. S., ... Rebbeck, T. R. (2012). Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. Journal of Clinical Oncology, 30(12), 1321-1328. https://doi.org/10.1200/JCO.2011.37.8133

Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. / Finkelman, Brian S.; Rubinstein, Wendy S.; Friedman, Sue; Friebel, Tara M.; Dubitsky, Shera; Schonberger, Niecee Singer; Shoretz, Rochelle; Singer, Christian F.; Blum, Joanne L.; Tung, Nadine; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Snyder, Carrie; Garber, Judy E.; Schildkraut, Joellen; Daly, Mary B.; Isaacs, Claudine; Pichert, Gabrielle; Neuhausen, Susan L.; Couch, Fergus J.; Van't Veer, Laura; Eeles, Rosalind; Bancroft, Elizabeth; Evans, D. Gareth; Ganz, Patricia A.; Tomlinson, Gail E.; Narod, Steven A.; Matloff, Ellen; Domchek, Susan; Rebbeck, Timothy R.

In: Journal of Clinical Oncology, Vol. 30, No. 12, 20.04.2012, p. 1321-1328.

Research output: Contribution to journalArticle

Finkelman, BS, Rubinstein, WS, Friedman, S, Friebel, TM, Dubitsky, S, Schonberger, NS, Shoretz, R, Singer, CF, Blum, JL, Tung, N, Olopade, OI, Weitzel, JN, Lynch, HT, Snyder, C, Garber, JE, Schildkraut, J, Daly, MB, Isaacs, C, Pichert, G, Neuhausen, SL, Couch, FJ, Van't Veer, L, Eeles, R, Bancroft, E, Evans, DG, Ganz, PA, Tomlinson, GE, Narod, SA, Matloff, E, Domchek, S & Rebbeck, TR 2012, 'Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers', Journal of Clinical Oncology, vol. 30, no. 12, pp. 1321-1328. https://doi.org/10.1200/JCO.2011.37.8133
Finkelman BS, Rubinstein WS, Friedman S, Friebel TM, Dubitsky S, Schonberger NS et al. Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. Journal of Clinical Oncology. 2012 Apr 20;30(12):1321-1328. https://doi.org/10.1200/JCO.2011.37.8133
Finkelman, Brian S. ; Rubinstein, Wendy S. ; Friedman, Sue ; Friebel, Tara M. ; Dubitsky, Shera ; Schonberger, Niecee Singer ; Shoretz, Rochelle ; Singer, Christian F. ; Blum, Joanne L. ; Tung, Nadine ; Olopade, Olufunmilayo I. ; Weitzel, Jeffrey N. ; Lynch, Henry T. ; Snyder, Carrie ; Garber, Judy E. ; Schildkraut, Joellen ; Daly, Mary B. ; Isaacs, Claudine ; Pichert, Gabrielle ; Neuhausen, Susan L. ; Couch, Fergus J. ; Van't Veer, Laura ; Eeles, Rosalind ; Bancroft, Elizabeth ; Evans, D. Gareth ; Ganz, Patricia A. ; Tomlinson, Gail E. ; Narod, Steven A. ; Matloff, Ellen ; Domchek, Susan ; Rebbeck, Timothy R. / Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 12. pp. 1321-1328.
@article{7a60e4a3b94c4130a0b8276419bdc9f8,
title = "Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers",
abstract = "Purpose: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54{\%} v 41{\%}, respectively; odds ratio, 1.87; 95{\%} CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95{\%} CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.",
author = "Finkelman, {Brian S.} and Rubinstein, {Wendy S.} and Sue Friedman and Friebel, {Tara M.} and Shera Dubitsky and Schonberger, {Niecee Singer} and Rochelle Shoretz and Singer, {Christian F.} and Blum, {Joanne L.} and Nadine Tung and Olopade, {Olufunmilayo I.} and Weitzel, {Jeffrey N.} and Lynch, {Henry T.} and Carrie Snyder and Garber, {Judy E.} and Joellen Schildkraut and Daly, {Mary B.} and Claudine Isaacs and Gabrielle Pichert and Neuhausen, {Susan L.} and Couch, {Fergus J.} and {Van't Veer}, Laura and Rosalind Eeles and Elizabeth Bancroft and Evans, {D. Gareth} and Ganz, {Patricia A.} and Tomlinson, {Gail E.} and Narod, {Steven A.} and Ellen Matloff and Susan Domchek and Rebbeck, {Timothy R.}",
year = "2012",
month = "4",
day = "20",
doi = "10.1200/JCO.2011.37.8133",
language = "English",
volume = "30",
pages = "1321--1328",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "12",

}

TY - JOUR

T1 - Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers

AU - Finkelman, Brian S.

AU - Rubinstein, Wendy S.

AU - Friedman, Sue

AU - Friebel, Tara M.

AU - Dubitsky, Shera

AU - Schonberger, Niecee Singer

AU - Shoretz, Rochelle

AU - Singer, Christian F.

AU - Blum, Joanne L.

AU - Tung, Nadine

AU - Olopade, Olufunmilayo I.

AU - Weitzel, Jeffrey N.

AU - Lynch, Henry T.

AU - Snyder, Carrie

AU - Garber, Judy E.

AU - Schildkraut, Joellen

AU - Daly, Mary B.

AU - Isaacs, Claudine

AU - Pichert, Gabrielle

AU - Neuhausen, Susan L.

AU - Couch, Fergus J.

AU - Van't Veer, Laura

AU - Eeles, Rosalind

AU - Bancroft, Elizabeth

AU - Evans, D. Gareth

AU - Ganz, Patricia A.

AU - Tomlinson, Gail E.

AU - Narod, Steven A.

AU - Matloff, Ellen

AU - Domchek, Susan

AU - Rebbeck, Timothy R.

PY - 2012/4/20

Y1 - 2012/4/20

N2 - Purpose: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

AB - Purpose: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

UR - http://www.scopus.com/inward/record.url?scp=84862255120&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862255120&partnerID=8YFLogxK

U2 - 10.1200/JCO.2011.37.8133

DO - 10.1200/JCO.2011.37.8133

M3 - Article

VL - 30

SP - 1321

EP - 1328

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 12

ER -