Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

E Sawyer; R Roylance; C Petridis; MN Brook; S Nowinski; E Papouli; O Fletcher; S Pinder; A Hanby; K Kohut; P Gorman; M Caneppele; J Peto; ID Silva; N Johnson; R Swann; M Dwek; KA Perkins; C Gillett; R Houlston; G Ross; P De Ieso; MC Southey; JL Hopper; E Provenzano; C Apicella; J Wesseling; S Cornelissen; R Keeman; PA Fasching; SM Jud; AB Ekici; MW Beckmann; MJ Kerin; F Marme; A Schneeweiss; C Sohn; B Burwinkel; P Guenel; P Laurent-Puig; P Kerbrat; SE Bojesen; BG Nordestgaard; SF Nielsen; H Flyger; RL Milne; JIA Perez; P Menendez; J Benitez; H Brenner; AK Dieffenbach; V Arndt; C Stegmaier; A Meindl; P Lichtner; RK Schmutzler; M Lochmann; H Brauch; HP Fischer; YD Ko; H Nevanlinna; TA Muranen; K Aittomaki; C Blomqvist; NV Bogdanova; T Dork; A Lindblom; S Margolin; A Mannermaa; V Kataja; VM Kosma; JM Hartikainen; G Chenevix-Trench; D Lambrechts; C Weltens; E van Limbergen; S Hatse; J Chang-Claude; A Rudolph; P Seibold; D Flesch-Janys; P Radice; P Peterlongo; B Bonanni; S Volorio; GG Giles; G Severi; L Baglietto; CA McLean; CA Haiman; BE Henderson; F Schumacher; L Le Marchand; J Simard; MS Goldberg; F Labreche; M Dumont; V Kristensen; R Winqvist; K Pylkas; A Jukkola-Vuorinen; S Kauppila; IL Andrulis; JA Knight; G Glendon; AM Mulligan; P Devillee; RAEM Tollenaar; Caroline Seynaeve; Mieke Kriege; J Figueroa; SJ Chanock; ME Sherman; Maartje Hooning; Antoinette Hollestelle; Ans van den Ouweland; Carolien van Deurzen; JM Li; K Czene; K Humphreys; A Cox; SS Cross; MWR Reed; M Shah; A Jakubowska; J Lubinski; K Jaworska-Bieniek; K Durda; A Swerdlow; A Ashworth; N Orr; M Schoemaker; FJ Couch; E Hallberg; A Gonzalez-Neira; G Pita; MR Alonso; DC Tessier; D Vincent; F Bacot; MK Bolla; Q (Qing) Wang; J Dennis; K Michailidou; AM Dunning; P Hall; D Easton; P Pharoah; Marjanka K Schmidt; I Tomlinson; M Garcia-Closas

doi:10.1371/journal.pgen.1004285

Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

E Sawyer, R Roylance, C Petridis, MN Brook, S Nowinski, E Papouli, O Fletcher, S Pinder, A Hanby, K Kohut, P Gorman, M Caneppele, J Peto, ID Silva, N Johnson, R Swann, M Dwek, KA Perkins, C Gillett, R HoulstonG Ross, P De Ieso, MC Southey, JL Hopper, E Provenzano, C Apicella, J Wesseling, S Cornelissen, R Keeman, PA Fasching, SM Jud, AB Ekici, MW Beckmann, MJ Kerin, F Marme, A Schneeweiss, C Sohn, B Burwinkel, P Guenel, P Laurent-Puig, P Kerbrat, SE Bojesen, BG Nordestgaard, SF Nielsen, H Flyger, RL Milne, JIA Perez, P Menendez, J Benitez, H Brenner, AK Dieffenbach, V Arndt, C Stegmaier, A Meindl, P Lichtner, RK Schmutzler, M Lochmann, H Brauch, HP Fischer, YD Ko, H Nevanlinna, TA Muranen, K Aittomaki, C Blomqvist, NV Bogdanova, T Dork, A Lindblom, S Margolin, A Mannermaa, V Kataja, VM Kosma, JM Hartikainen, G Chenevix-Trench, D Lambrechts, C Weltens, E van Limbergen, S Hatse, J Chang-Claude, A Rudolph, P Seibold, D Flesch-Janys, P Radice, P Peterlongo, B Bonanni, S Volorio, GG Giles, G Severi, L Baglietto, CA McLean, CA Haiman, BE Henderson, F Schumacher, L Le Marchand, J Simard, MS Goldberg, F Labreche, M Dumont, V Kristensen, R Winqvist, K Pylkas, A Jukkola-Vuorinen, S Kauppila, IL Andrulis, JA Knight, G Glendon, AM Mulligan, P Devillee, RAEM Tollenaar, Caroline Seynaeve, Mieke Kriege, J Figueroa, SJ Chanock, ME Sherman, Maartje Hooning, Antoinette Hollestelle, Ans van den Ouweland, Carolien van Deurzen, JM Li, K Czene, K Humphreys, A Cox, SS Cross, MWR Reed, M Shah, A Jakubowska, J Lubinski, K Jaworska-Bieniek, K Durda, A Swerdlow, A Ashworth, N Orr, M Schoemaker, FJ Couch, E Hallberg, A Gonzalez-Neira, G Pita, MR Alonso, DC Tessier, D Vincent, F Bacot, MK Bolla, Q (Qing) Wang, J Dennis, K Michailidou, AM Dunning, P Hall, D Easton, P Pharoah, Marjanka K Schmidt, I Tomlinson, M Garcia-Closas

Research output: Contribution to journal › Article › Academic › peer-review

35 Citations (Scopus)

Abstract

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

Original language	Undefined/Unknown
Journal	PLoS Genetics (print)
Volume	10
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1004285
Publication status	Published - 2014

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10.1371/journal.pgen.1004285

http://hdl.handle.net/1765/56552

Cite this

Sawyer, E., Roylance, R., Petridis, C., Brook, MN., Nowinski, S., Papouli, E., Fletcher, O., Pinder, S., Hanby, A., Kohut, K., Gorman, P., Caneppele, M., Peto, J., Silva, ID., Johnson, N., Swann, R., Dwek, M., Perkins, KA., Gillett, C., ... Garcia-Closas, M. (2014). Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast. PLoS Genetics (print), 10(4). https://doi.org/10.1371/journal.pgen.1004285

@article{8abbac6cb3cd4c5a8e9a7d17e0bf83f3,

title = "Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast",

abstract = "Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.",

author = "E Sawyer and R Roylance and C Petridis and MN Brook and S Nowinski and E Papouli and O Fletcher and S Pinder and A Hanby and K Kohut and P Gorman and M Caneppele and J Peto and ID Silva and N Johnson and R Swann and M Dwek and KA Perkins and C Gillett and R Houlston and G Ross and {De Ieso}, P and MC Southey and JL Hopper and E Provenzano and C Apicella and J Wesseling and S Cornelissen and R Keeman and PA Fasching and SM Jud and AB Ekici and MW Beckmann and MJ Kerin and F Marme and A Schneeweiss and C Sohn and B Burwinkel and P Guenel and P Laurent-Puig and P Kerbrat and SE Bojesen and BG Nordestgaard and SF Nielsen and H Flyger and RL Milne and JIA Perez and P Menendez and J Benitez and H Brenner and AK Dieffenbach and V Arndt and C Stegmaier and A Meindl and P Lichtner and RK Schmutzler and M Lochmann and H Brauch and HP Fischer and YD Ko and H Nevanlinna and TA Muranen and K Aittomaki and C Blomqvist and NV Bogdanova and T Dork and A Lindblom and S Margolin and A Mannermaa and V Kataja and VM Kosma and JM Hartikainen and G Chenevix-Trench and D Lambrechts and C Weltens and {van Limbergen}, E and S Hatse and J Chang-Claude and A Rudolph and P Seibold and D Flesch-Janys and P Radice and P Peterlongo and B Bonanni and S Volorio and GG Giles and G Severi and L Baglietto and CA McLean and CA Haiman and BE Henderson and F Schumacher and {Le Marchand}, L and J Simard and MS Goldberg and F Labreche and M Dumont and V Kristensen and R Winqvist and K Pylkas and A Jukkola-Vuorinen and S Kauppila and IL Andrulis and JA Knight and G Glendon and AM Mulligan and P Devillee and RAEM Tollenaar and Caroline Seynaeve and Mieke Kriege and J Figueroa and SJ Chanock and ME Sherman and Maartje Hooning and Antoinette Hollestelle and {van den Ouweland}, Ans and {van Deurzen}, Carolien and JM Li and K Czene and K Humphreys and A Cox and SS Cross and MWR Reed and M Shah and A Jakubowska and J Lubinski and K Jaworska-Bieniek and K Durda and A Swerdlow and A Ashworth and N Orr and M Schoemaker and FJ Couch and E Hallberg and A Gonzalez-Neira and G Pita and MR Alonso and DC Tessier and D Vincent and F Bacot and MK Bolla and Wang, {Q (Qing)} and J Dennis and K Michailidou and AM Dunning and P Hall and D Easton and P Pharoah and Schmidt, {Marjanka K} and I Tomlinson and M Garcia-Closas",

year = "2014",

doi = "10.1371/journal.pgen.1004285",

language = "Undefined/Unknown",

volume = "10",

journal = "PLoS Genetics (print)",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "4",

}

Sawyer, E, Roylance, R, Petridis, C, Brook, MN, Nowinski, S, Papouli, E, Fletcher, O, Pinder, S, Hanby, A, Kohut, K, Gorman, P, Caneppele, M, Peto, J, Silva, ID, Johnson, N, Swann, R, Dwek, M, Perkins, KA, Gillett, C, Houlston, R, Ross, G, De Ieso, P, Southey, MC, Hopper, JL, Provenzano, E, Apicella, C, Wesseling, J, Cornelissen, S, Keeman, R, Fasching, PA, Jud, SM, Ekici, AB, Beckmann, MW, Kerin, MJ, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Laurent-Puig, P, Kerbrat, P, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Milne, RL, Perez, JIA, Menendez, P, Benitez, J, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Meindl, A, Lichtner, P, Schmutzler, RK, Lochmann, M, Brauch, H, Fischer, HP, Ko, YD, Nevanlinna, H, Muranen, TA, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Dork, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Chenevix-Trench, G, Lambrechts, D, Weltens, C, van Limbergen, E, Hatse, S, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Bonanni, B, Volorio, S, Giles, GG, Severi, G, Baglietto, L, McLean, CA, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, MS, Labreche, F, Dumont, M, Kristensen, V, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Devillee, P, Tollenaar, RAEM, Seynaeve, C, Kriege, M, Figueroa, J, Chanock, SJ, Sherman, ME, Hooning, M, Hollestelle, A, van den Ouweland, A, van Deurzen, C, Li, JM, Czene, K, Humphreys, K, Cox, A, Cross, SS, Reed, MWR, Shah, M, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, M, Couch, FJ, Hallberg, E, Gonzalez-Neira, A, Pita, G, Alonso, MR, Tessier, DC, Vincent, D, Bacot, F, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Dunning, AM, Hall, P, Easton, D, Pharoah, P, Schmidt, MK, Tomlinson, I & Garcia-Closas, M 2014, 'Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast', PLoS Genetics (print), vol. 10, no. 4. https://doi.org/10.1371/journal.pgen.1004285

TY - JOUR

T1 - Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

AU - Sawyer, E

AU - Roylance, R

AU - Petridis, C

AU - Brook, MN

AU - Nowinski, S

AU - Papouli, E

AU - Fletcher, O

AU - Pinder, S

AU - Hanby, A

AU - Kohut, K

AU - Gorman, P

AU - Caneppele, M

AU - Peto, J

AU - Silva, ID

AU - Johnson, N

AU - Swann, R

AU - Dwek, M

AU - Perkins, KA

AU - Gillett, C

AU - Houlston, R

AU - Ross, G

AU - De Ieso, P

AU - Southey, MC

AU - Hopper, JL

AU - Provenzano, E

AU - Apicella, C

AU - Wesseling, J

AU - Cornelissen, S

AU - Keeman, R

AU - Fasching, PA

AU - Jud, SM

AU - Ekici, AB

AU - Beckmann, MW

AU - Kerin, MJ

AU - Marme, F

AU - Schneeweiss, A

AU - Sohn, C

AU - Burwinkel, B

AU - Guenel, P

AU - Laurent-Puig, P

AU - Kerbrat, P

AU - Bojesen, SE

AU - Nordestgaard, BG

AU - Nielsen, SF

AU - Flyger, H

AU - Milne, RL

AU - Perez, JIA

AU - Menendez, P

AU - Benitez, J

AU - Brenner, H

AU - Dieffenbach, AK

AU - Arndt, V

AU - Stegmaier, C

AU - Meindl, A

AU - Lichtner, P

AU - Schmutzler, RK

AU - Lochmann, M

AU - Brauch, H

AU - Fischer, HP

AU - Ko, YD

AU - Nevanlinna, H

AU - Muranen, TA

AU - Aittomaki, K

AU - Blomqvist, C

AU - Bogdanova, NV

AU - Dork, T

AU - Lindblom, A

AU - Margolin, S

AU - Mannermaa, A

AU - Kataja, V

AU - Kosma, VM

AU - Hartikainen, JM

AU - Chenevix-Trench, G

AU - Lambrechts, D

AU - Weltens, C

AU - van Limbergen, E

AU - Hatse, S

AU - Chang-Claude, J

AU - Rudolph, A

AU - Seibold, P

AU - Flesch-Janys, D

AU - Radice, P

AU - Peterlongo, P

AU - Bonanni, B

AU - Volorio, S

AU - Giles, GG

AU - Severi, G

AU - Baglietto, L

AU - McLean, CA

AU - Haiman, CA

AU - Henderson, BE

AU - Schumacher, F

AU - Le Marchand, L

AU - Simard, J

AU - Goldberg, MS

AU - Labreche, F

AU - Dumont, M

AU - Kristensen, V

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Kauppila, S

AU - Andrulis, IL

AU - Knight, JA

AU - Glendon, G

AU - Mulligan, AM

AU - Devillee, P

AU - Tollenaar, RAEM

AU - Seynaeve, Caroline

AU - Kriege, Mieke

AU - Figueroa, J

AU - Chanock, SJ

AU - Sherman, ME

AU - Hooning, Maartje

AU - Hollestelle, Antoinette

AU - van den Ouweland, Ans

AU - van Deurzen, Carolien

AU - Li, JM

AU - Czene, K

AU - Humphreys, K

AU - Cox, A

AU - Cross, SS

AU - Reed, MWR

AU - Shah, M

AU - Jakubowska, A

AU - Lubinski, J

AU - Jaworska-Bieniek, K

AU - Durda, K

AU - Swerdlow, A

AU - Ashworth, A

AU - Orr, N

AU - Schoemaker, M

AU - Couch, FJ

AU - Hallberg, E

AU - Gonzalez-Neira, A

AU - Pita, G

AU - Alonso, MR

AU - Tessier, DC

AU - Vincent, D

AU - Bacot, F

AU - Bolla, MK

AU - Wang, Q (Qing)

AU - Dennis, J

AU - Michailidou, K

AU - Dunning, AM

AU - Hall, P

AU - Easton, D

AU - Pharoah, P

AU - Schmidt, Marjanka K

AU - Tomlinson, I

AU - Garcia-Closas, M

PY - 2014

Y1 - 2014

N2 - Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

AB - Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

U2 - 10.1371/journal.pgen.1004285

DO - 10.1371/journal.pgen.1004285

M3 - Article

C2 - 24743323

SN - 1553-7390

VL - 10

JO - PLoS Genetics (print)

JF - PLoS Genetics (print)

IS - 4

ER -