RAD51B in familial breast cancer

Liisa M. Pelttari; Sofia Khan; Mikko Vuorela; Johanna I. Kiiski; Sara Vilske; Viivi Nevanlinna; Salla Ranta; Johanna Schleutker; Rober Winqvist; Anne Kallioniemi; Thilo Dörk; Natalia V. Bogdanova; Jonine Figueroa; Paul D. P. Pharoah; Marjanka K. Schmidt; Alison M. Dunning; Montserrat García-Closas; Manjeet K. Bolla; Joe Dennis; Kyriaki Michailidou; Qin Wang; John L. Hopper; Melissa C. Southey; Efraim H. Rosenberg; Peter A. Fasching; Matthias W. Beckmann; Julian Peto; Isabel dos-Santos-Silva; Elinor J. Sawyer; Ian Tomlinson; Barbara Burwinkel; Harald Surowy; Pascal Guénel; Therese Truong; Stig E. Bojesen; Borge G Nordestgaard; Javier Benitez; Anna González-Neira; Susan L. Neuhausen; Hoda Anton-Culver; Hermann Brenner; Volker Arndt; Alfons Meindl; Rita K. Schmutzler; Hiltrud Brauch; Thomas Brüning; Annika Lindblom; Sara Margolin; Arto Mannermaa; Jaana M. Hartikainen; L. Anderson; null et al

doi:10.1371/journal.pone.0153788

RAD51B in familial breast cancer

Liisa M. Pelttari, Sofia Khan, Mikko Vuorela, Johanna I. Kiiski, Sara Vilske, Viivi Nevanlinna, Salla Ranta, Johanna Schleutker, Rober Winqvist, Anne Kallioniemi, Thilo Dörk, Natalia V. Bogdanova, Jonine Figueroa, Paul D. P. Pharoah, Marjanka K. Schmidt, Alison M. Dunning, Montserrat García-Closas, Manjeet K. Bolla, Joe Dennis, Kyriaki MichailidouQin Wang, John L. Hopper, Melissa C. Southey, Efraim H. Rosenberg, Peter A. Fasching, Matthias W. Beckmann, Julian Peto, Isabel dos-Santos-Silva, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Harald Surowy, Pascal Guénel, Therese Truong, Stig E. Bojesen, Borge G Nordestgaard, Javier Benitez, Anna González-Neira, Susan L. Neuhausen, Hoda Anton-Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Thomas Brüning, Annika Lindblom, Sara Margolin, Arto Mannermaa, Jaana M. Hartikainen, L. Anderson, et al

Western Sydney University

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Abstract

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

Original language	English
Article number	e0153788
Number of pages	18
Journal	PLoS One
Volume	11
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0153788
Publication status	Published - 2016

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10.1371/journal.pone.0153788

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Pelttari, L. M., Khan, S., Vuorela, M., Kiiski, J. I., Vilske, S., Nevanlinna, V., Ranta, S., Schleutker, J., Winqvist, R., Kallioniemi, A., Dörk, T., Bogdanova, N. V., Figueroa, J., Pharoah, P. D. P., Schmidt, M. K., Dunning, A. M., García-Closas, M., Bolla, M. K., Dennis, J., ... et al (2016). RAD51B in familial breast cancer. PLoS One, 11(5), Article e0153788. https://doi.org/10.1371/journal.pone.0153788

@article{64d398ec1bd44b1d9063d02a869a9a94,

title = "RAD51B in familial breast cancer",

abstract = "Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.",

author = "Pelttari, {Liisa M.} and Sofia Khan and Mikko Vuorela and Kiiski, {Johanna I.} and Sara Vilske and Viivi Nevanlinna and Salla Ranta and Johanna Schleutker and Rober Winqvist and Anne Kallioniemi and Thilo D{\"o}rk and Bogdanova, {Natalia V.} and Jonine Figueroa and Pharoah, {Paul D. P.} and Schmidt, {Marjanka K.} and Dunning, {Alison M.} and Montserrat Garc{\'i}a-Closas and Bolla, {Manjeet K.} and Joe Dennis and Kyriaki Michailidou and Qin Wang and Hopper, {John L.} and Southey, {Melissa C.} and Rosenberg, {Efraim H.} and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Julian Peto and Isabel dos-Santos-Silva and Sawyer, {Elinor J.} and Ian Tomlinson and Barbara Burwinkel and Harald Surowy and Pascal Gu{\'e}nel and Therese Truong and Bojesen, {Stig E.} and Nordestgaard, {Borge G} and Javier Benitez and Anna Gonz{\'a}lez-Neira and Neuhausen, {Susan L.} and Hoda Anton-Culver and Hermann Brenner and Volker Arndt and Alfons Meindl and Schmutzler, {Rita K.} and Hiltrud Brauch and Thomas Br{\"u}ning and Annika Lindblom and Sara Margolin and Arto Mannermaa and Hartikainen, {Jaana M.} and L. Anderson and {et al}",

year = "2016",

doi = "10.1371/journal.pone.0153788",

language = "English",

volume = "11",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Pelttari, LM, Khan, S, Vuorela, M, Kiiski, JI, Vilske, S, Nevanlinna, V, Ranta, S, Schleutker, J, Winqvist, R, Kallioniemi, A, Dörk, T, Bogdanova, NV, Figueroa, J, Pharoah, PDP, Schmidt, MK, Dunning, AM, García-Closas, M, Bolla, MK, Dennis, J, Michailidou, K, Wang, Q, Hopper, JL, Southey, MC, Rosenberg, EH, Fasching, PA, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Surowy, H, Guénel, P, Truong, T, Bojesen, SE, Nordestgaard, BG, Benitez, J, González-Neira, A, Neuhausen, SL, Anton-Culver, H, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Brüning, T, Lindblom, A, Margolin, S, Mannermaa, A, Hartikainen, JM, Anderson, L & et al 2016, 'RAD51B in familial breast cancer', PLoS One, vol. 11, no. 5, e0153788. https://doi.org/10.1371/journal.pone.0153788

TY - JOUR

T1 - RAD51B in familial breast cancer

AU - Pelttari, Liisa M.

AU - Khan, Sofia

AU - Vuorela, Mikko

AU - Kiiski, Johanna I.

AU - Vilske, Sara

AU - Nevanlinna, Viivi

AU - Ranta, Salla

AU - Schleutker, Johanna

AU - Winqvist, Rober

AU - Kallioniemi, Anne

AU - Dörk, Thilo

AU - Bogdanova, Natalia V.

AU - Figueroa, Jonine

AU - Pharoah, Paul D. P.

AU - Schmidt, Marjanka K.

AU - Dunning, Alison M.

AU - García-Closas, Montserrat

AU - Bolla, Manjeet K.

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - Wang, Qin

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Rosenberg, Efraim H.

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Peto, Julian

AU - dos-Santos-Silva, Isabel

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Burwinkel, Barbara

AU - Surowy, Harald

AU - Guénel, Pascal

AU - Truong, Therese

AU - Bojesen, Stig E.

AU - Nordestgaard, Borge G

AU - Benitez, Javier

AU - González-Neira, Anna

AU - Neuhausen, Susan L.

AU - Anton-Culver, Hoda

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Meindl, Alfons

AU - Schmutzler, Rita K.

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Hartikainen, Jaana M.

AU - Anderson, L.

AU - et al, null

PY - 2016

Y1 - 2016

N2 - Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

AB - Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

UR - https://hdl.handle.net/1959.7/uws:67035

U2 - 10.1371/journal.pone.0153788

DO - 10.1371/journal.pone.0153788

M3 - Article

SN - 1932-6203

VL - 11

JO - PLoS One

JF - PLoS One

IS - 5

M1 - e0153788

ER -

RAD51B in familial breast cancer

Abstract

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