Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium

Deborah Thompson, Csilla I. Szabo, Jon Mangion, Rogier A. Oldenburg, Fabrice Odefrey, Sheila Seal, Rita Barfoot, Karin Kroeze-Jansema, Dawn Teare, Nazneen Rahman, Hélène Renard, Graham Mann, John L. Hopper, Saundra S. Buys, Irene L. Andrulis, Ruby Senie, Mary B. Daly, Dee West, Elaine A. Ostrander, Ken Offit & 28 others Tamar Peretz, Ana Osorio, J. Benitez, Katherine L. Nathanson, Olga M. Sinilnikova, Edith Olàh, Yves Jean Bignon, Pablo Ruiz, Michael D. Badzioch, Hans F A Vasen, Andrew P. Futreal, Catherine M. Phelan, Steven A. Narod, Henry T. Lynch, Bruce A J Ponder, Ros A. Eeles, Hanne Meijers-Heijboer, Dominique Stoppa-Lyonnet, Fergus J. Couch, Diana M. Eccles, D. Gareth Evans, Jenny Chang-Claude, Gilbert Lenoir, Barbara L. Weber, Peter Devilee, Douglas F. Easton, David E. Goldgar, Michael R. Stratton

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Abstract

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

Original languageEnglish
Pages (from-to)827-831
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number2
DOIs
StatePublished - Jan 22 2002

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Chromosomes
Breast Neoplasms
Scandinavian and Nordic Countries
Genetic Markers
Genes
Mutation

All Science Journal Classification (ASJC) codes

  • Genetics
  • General

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Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium. / Thompson, Deborah; Szabo, Csilla I.; Mangion, Jon; Oldenburg, Rogier A.; Odefrey, Fabrice; Seal, Sheila; Barfoot, Rita; Kroeze-Jansema, Karin; Teare, Dawn; Rahman, Nazneen; Renard, Hélène; Mann, Graham; Hopper, John L.; Buys, Saundra S.; Andrulis, Irene L.; Senie, Ruby; Daly, Mary B.; West, Dee; Ostrander, Elaine A.; Offit, Ken; Peretz, Tamar; Osorio, Ana; Benitez, J.; Nathanson, Katherine L.; Sinilnikova, Olga M.; Olàh, Edith; Bignon, Yves Jean; Ruiz, Pablo; Badzioch, Michael D.; Vasen, Hans F A; Futreal, Andrew P.; Phelan, Catherine M.; Narod, Steven A.; Lynch, Henry T.; Ponder, Bruce A J; Eeles, Ros A.; Meijers-Heijboer, Hanne; Stoppa-Lyonnet, Dominique; Couch, Fergus J.; Eccles, Diana M.; Evans, D. Gareth; Chang-Claude, Jenny; Lenoir, Gilbert; Weber, Barbara L.; Devilee, Peter; Easton, Douglas F.; Goldgar, David E.; Stratton, Michael R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 2, 22.01.2002, p. 827-831.

Research output: Contribution to journalArticle

Thompson, D, Szabo, CI, Mangion, J, Oldenburg, RA, Odefrey, F, Seal, S, Barfoot, R, Kroeze-Jansema, K, Teare, D, Rahman, N, Renard, H, Mann, G, Hopper, JL, Buys, SS, Andrulis, IL, Senie, R, Daly, MB, West, D, Ostrander, EA, Offit, K, Peretz, T, Osorio, A, Benitez, J, Nathanson, KL, Sinilnikova, OM, Olàh, E, Bignon, YJ, Ruiz, P, Badzioch, MD, Vasen, HFA, Futreal, AP, Phelan, CM, Narod, SA, Lynch, HT, Ponder, BAJ, Eeles, RA, Meijers-Heijboer, H, Stoppa-Lyonnet, D, Couch, FJ, Eccles, DM, Evans, DG, Chang-Claude, J, Lenoir, G, Weber, BL, Devilee, P, Easton, DF, Goldgar, DE & Stratton, MR 2002, 'Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 2, pp. 827-831. https://doi.org/10.1073/pnas.012584499
Thompson, Deborah ; Szabo, Csilla I. ; Mangion, Jon ; Oldenburg, Rogier A. ; Odefrey, Fabrice ; Seal, Sheila ; Barfoot, Rita ; Kroeze-Jansema, Karin ; Teare, Dawn ; Rahman, Nazneen ; Renard, Hélène ; Mann, Graham ; Hopper, John L. ; Buys, Saundra S. ; Andrulis, Irene L. ; Senie, Ruby ; Daly, Mary B. ; West, Dee ; Ostrander, Elaine A. ; Offit, Ken ; Peretz, Tamar ; Osorio, Ana ; Benitez, J. ; Nathanson, Katherine L. ; Sinilnikova, Olga M. ; Olàh, Edith ; Bignon, Yves Jean ; Ruiz, Pablo ; Badzioch, Michael D. ; Vasen, Hans F A ; Futreal, Andrew P. ; Phelan, Catherine M. ; Narod, Steven A. ; Lynch, Henry T. ; Ponder, Bruce A J ; Eeles, Ros A. ; Meijers-Heijboer, Hanne ; Stoppa-Lyonnet, Dominique ; Couch, Fergus J. ; Eccles, Diana M. ; Evans, D. Gareth ; Chang-Claude, Jenny ; Lenoir, Gilbert ; Weber, Barbara L. ; Devilee, Peter ; Easton, Douglas F. ; Goldgar, David E. ; Stratton, Michael R. / Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 2. pp. 827-831.
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title = "Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium",
abstract = "The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate {"}BRCA3{"} locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95{\%} confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95{\%} confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.",
author = "Deborah Thompson and Szabo, {Csilla I.} and Jon Mangion and Oldenburg, {Rogier A.} and Fabrice Odefrey and Sheila Seal and Rita Barfoot and Karin Kroeze-Jansema and Dawn Teare and Nazneen Rahman and H{\'e}l{\`e}ne Renard and Graham Mann and Hopper, {John L.} and Buys, {Saundra S.} and Andrulis, {Irene L.} and Ruby Senie and Daly, {Mary B.} and Dee West and Ostrander, {Elaine A.} and Ken Offit and Tamar Peretz and Ana Osorio and J. Benitez and Nathanson, {Katherine L.} and Sinilnikova, {Olga M.} and Edith Ol{\`a}h and Bignon, {Yves Jean} and Pablo Ruiz and Badzioch, {Michael D.} and Vasen, {Hans F A} and Futreal, {Andrew P.} and Phelan, {Catherine M.} and Narod, {Steven A.} and Lynch, {Henry T.} and Ponder, {Bruce A J} and Eeles, {Ros A.} and Hanne Meijers-Heijboer and Dominique Stoppa-Lyonnet and Couch, {Fergus J.} and Eccles, {Diana M.} and Evans, {D. Gareth} and Jenny Chang-Claude and Gilbert Lenoir and Weber, {Barbara L.} and Peter Devilee and Easton, {Douglas F.} and Goldgar, {David E.} and Stratton, {Michael R.}",
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T1 - Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium

AU - Thompson, Deborah

AU - Szabo, Csilla I.

AU - Mangion, Jon

AU - Oldenburg, Rogier A.

AU - Odefrey, Fabrice

AU - Seal, Sheila

AU - Barfoot, Rita

AU - Kroeze-Jansema, Karin

AU - Teare, Dawn

AU - Rahman, Nazneen

AU - Renard, Hélène

AU - Mann, Graham

AU - Hopper, John L.

AU - Buys, Saundra S.

AU - Andrulis, Irene L.

AU - Senie, Ruby

AU - Daly, Mary B.

AU - West, Dee

AU - Ostrander, Elaine A.

AU - Offit, Ken

AU - Peretz, Tamar

AU - Osorio, Ana

AU - Benitez, J.

AU - Nathanson, Katherine L.

AU - Sinilnikova, Olga M.

AU - Olàh, Edith

AU - Bignon, Yves Jean

AU - Ruiz, Pablo

AU - Badzioch, Michael D.

AU - Vasen, Hans F A

AU - Futreal, Andrew P.

AU - Phelan, Catherine M.

AU - Narod, Steven A.

AU - Lynch, Henry T.

AU - Ponder, Bruce A J

AU - Eeles, Ros A.

AU - Meijers-Heijboer, Hanne

AU - Stoppa-Lyonnet, Dominique

AU - Couch, Fergus J.

AU - Eccles, Diana M.

AU - Evans, D. Gareth

AU - Chang-Claude, Jenny

AU - Lenoir, Gilbert

AU - Weber, Barbara L.

AU - Devilee, Peter

AU - Easton, Douglas F.

AU - Goldgar, David E.

AU - Stratton, Michael R.

PY - 2002/1/22

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N2 - The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

AB - The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

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