Genetic predisposition to ductal carcinoma in situ of the breast

C Petridis; MN Brook; V Shah; K Kohut; P Gorman; M Caneppele; D Levi; E Papouli; N Orr; A Cox; SS Cross; I dos-Santos-Silva; J Peto; A Swerdlow; MJ Schoemaker; MK Bolla; Q Wang; J Dennis; K Michailidou; J Benitez; A Gonzalez-Neira; DC Tessier; D Vincent; JM Li; J Figueroa; V Kristensen; AL Borresen-Dale; P Soucy; J Simard; RL Milne; GG Giles; S Margolin; A Lindblom; T Bruning; H Brauch; MC Southey; JL Hopper; T Dork; NV Bogdanova; M Kabisch; U Hamann; RK Schmutzler; A Meindl; H Brenner; V Arndt; R Winqvist; K Pylkas; PA Fasching; MW Beckmann; J Lubinski; A Jakubowska; AM Mulligan; IL Andrulis; RAEM Tollenaar; P Devilee; L Le Marchand; CA Haiman; A Mannermaa; VM Kosma; P Radice; P Peterlongo; F Marme; B Burwinkel; Carolien van Deurzen; Antoinette Hollestelle; N Miller; MJ Kerin; D Lambrechts; G Floris; J Wesseling; H Flyger; SE Bojesen; S Yao; CB Ambrosone; G Chenevix-Trench; T Truong; P Guenel; A Rudolph; J Chang-Claude; H Nevanlinna; C Blomqvist; K Czene; JS Brand; JE Olson; FJ Couch; AM Dunning; P Hall; DF Easton; PDP Pharoah; SE Pinder; MK (Marjanka) Schmidt; I Tomlinson; R Roylance; M Garcia-Closas; EJ Sawyer

doi:10.1186/s13058-016-0675-7

Genetic predisposition to ductal carcinoma in situ of the breast

C Petridis, MN Brook, V Shah, K Kohut, P Gorman, M Caneppele, D Levi, E Papouli, N Orr, A Cox, SS Cross, I dos-Santos-Silva, J Peto, A Swerdlow, MJ Schoemaker, MK Bolla, Q Wang, J Dennis, K Michailidou, J BenitezA Gonzalez-Neira, DC Tessier, D Vincent, JM Li, J Figueroa, V Kristensen, AL Borresen-Dale, P Soucy, J Simard, RL Milne, GG Giles, S Margolin, A Lindblom, T Bruning, H Brauch, MC Southey, JL Hopper, T Dork, NV Bogdanova, M Kabisch, U Hamann, RK Schmutzler, A Meindl, H Brenner, V Arndt, R Winqvist, K Pylkas, PA Fasching, MW Beckmann, J Lubinski, A Jakubowska, AM Mulligan, IL Andrulis, RAEM Tollenaar, P Devilee, L Le Marchand, CA Haiman, A Mannermaa, VM Kosma, P Radice, P Peterlongo, F Marme, B Burwinkel, Carolien van Deurzen, Antoinette Hollestelle, N Miller, MJ Kerin, D Lambrechts, G Floris, J Wesseling, H Flyger, SE Bojesen, S Yao, CB Ambrosone, G Chenevix-Trench, T Truong, P Guenel, A Rudolph, J Chang-Claude, H Nevanlinna, C Blomqvist, K Czene, JS Brand, JE Olson, FJ Couch, AM Dunning, P Hall, DF Easton, PDP Pharoah, SE Pinder, MK (Marjanka) Schmidt, I Tomlinson, R Roylance, M Garcia-Closas, EJ Sawyer

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Abstract

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

Original language	Undefined/Unknown
Journal	Breast Cancer Research
Volume	18
DOIs	https://doi.org/10.1186/s13058-016-0675-7
Publication status	Published - 2016

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Petridis, C., Brook, MN., Shah, V., Kohut, K., Gorman, P., Caneppele, M., Levi, D., Papouli, E., Orr, N., Cox, A., Cross, SS., dos-Santos-Silva, I., Peto, J., Swerdlow, A., Schoemaker, MJ., Bolla, MK., Wang, Q., Dennis, J., Michailidou, K., ... Sawyer, EJ. (2016). Genetic predisposition to ductal carcinoma in situ of the breast. Breast Cancer Research, 18. https://doi.org/10.1186/s13058-016-0675-7

@article{74e6ba995333456ca551d39716aa8768,

title = "Genetic predisposition to ductal carcinoma in situ of the breast",

abstract = "Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.",

author = "C Petridis and MN Brook and V Shah and K Kohut and P Gorman and M Caneppele and D Levi and E Papouli and N Orr and A Cox and SS Cross and I dos-Santos-Silva and J Peto and A Swerdlow and MJ Schoemaker and MK Bolla and Q Wang and J Dennis and K Michailidou and J Benitez and A Gonzalez-Neira and DC Tessier and D Vincent and JM Li and J Figueroa and V Kristensen and AL Borresen-Dale and P Soucy and J Simard and RL Milne and GG Giles and S Margolin and A Lindblom and T Bruning and H Brauch and MC Southey and JL Hopper and T Dork and NV Bogdanova and M Kabisch and U Hamann and RK Schmutzler and A Meindl and H Brenner and V Arndt and R Winqvist and K Pylkas and PA Fasching and MW Beckmann and J Lubinski and A Jakubowska and AM Mulligan and IL Andrulis and RAEM Tollenaar and P Devilee and {Le Marchand}, L and CA Haiman and A Mannermaa and VM Kosma and P Radice and P Peterlongo and F Marme and B Burwinkel and {van Deurzen}, Carolien and Antoinette Hollestelle and N Miller and MJ Kerin and D Lambrechts and G Floris and J Wesseling and H Flyger and SE Bojesen and S Yao and CB Ambrosone and G Chenevix-Trench and T Truong and P Guenel and A Rudolph and J Chang-Claude and H Nevanlinna and C Blomqvist and K Czene and JS Brand and JE Olson and FJ Couch and AM Dunning and P Hall and DF Easton and PDP Pharoah and SE Pinder and Schmidt, {MK (Marjanka)} and I Tomlinson and R Roylance and M Garcia-Closas and EJ Sawyer",

year = "2016",

doi = "10.1186/s13058-016-0675-7",

language = "Undefined/Unknown",

volume = "18",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

}

Petridis, C, Brook, MN, Shah, V, Kohut, K, Gorman, P, Caneppele, M, Levi, D, Papouli, E, Orr, N, Cox, A, Cross, SS, dos-Santos-Silva, I, Peto, J, Swerdlow, A, Schoemaker, MJ, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Benitez, J, Gonzalez-Neira, A, Tessier, DC, Vincent, D, Li, JM, Figueroa, J, Kristensen, V, Borresen-Dale, AL, Soucy, P, Simard, J, Milne, RL, Giles, GG, Margolin, S, Lindblom, A, Bruning, T, Brauch, H, Southey, MC, Hopper, JL, Dork, T, Bogdanova, NV, Kabisch, M, Hamann, U, Schmutzler, RK, Meindl, A, Brenner, H, Arndt, V, Winqvist, R, Pylkas, K, Fasching, PA, Beckmann, MW, Lubinski, J, Jakubowska, A, Mulligan, AM, Andrulis, IL, Tollenaar, RAEM, Devilee, P, Le Marchand, L, Haiman, CA, Mannermaa, A, Kosma, VM, Radice, P, Peterlongo, P, Marme, F, Burwinkel, B, van Deurzen, C, Hollestelle, A, Miller, N, Kerin, MJ, Lambrechts, D, Floris, G, Wesseling, J, Flyger, H, Bojesen, SE, Yao, S, Ambrosone, CB, Chenevix-Trench, G, Truong, T, Guenel, P, Rudolph, A, Chang-Claude, J, Nevanlinna, H, Blomqvist, C, Czene, K, Brand, JS, Olson, JE, Couch, FJ, Dunning, AM, Hall, P, Easton, DF, Pharoah, PDP, Pinder, SE, Schmidt, MK, Tomlinson, I, Roylance, R, Garcia-Closas, M & Sawyer, EJ 2016, 'Genetic predisposition to ductal carcinoma in situ of the breast', Breast Cancer Research, vol. 18. https://doi.org/10.1186/s13058-016-0675-7

TY - JOUR

T1 - Genetic predisposition to ductal carcinoma in situ of the breast

AU - Petridis, C

AU - Brook, MN

AU - Shah, V

AU - Kohut, K

AU - Gorman, P

AU - Caneppele, M

AU - Levi, D

AU - Papouli, E

AU - Orr, N

AU - Cox, A

AU - Cross, SS

AU - dos-Santos-Silva, I

AU - Peto, J

AU - Swerdlow, A

AU - Schoemaker, MJ

AU - Bolla, MK

AU - Wang, Q

AU - Dennis, J

AU - Michailidou, K

AU - Benitez, J

AU - Gonzalez-Neira, A

AU - Tessier, DC

AU - Vincent, D

AU - Li, JM

AU - Figueroa, J

AU - Kristensen, V

AU - Borresen-Dale, AL

AU - Soucy, P

AU - Simard, J

AU - Milne, RL

AU - Giles, GG

AU - Margolin, S

AU - Lindblom, A

AU - Bruning, T

AU - Brauch, H

AU - Southey, MC

AU - Hopper, JL

AU - Dork, T

AU - Bogdanova, NV

AU - Kabisch, M

AU - Hamann, U

AU - Schmutzler, RK

AU - Meindl, A

AU - Brenner, H

AU - Arndt, V

AU - Winqvist, R

AU - Pylkas, K

AU - Fasching, PA

AU - Beckmann, MW

AU - Lubinski, J

AU - Jakubowska, A

AU - Mulligan, AM

AU - Andrulis, IL

AU - Tollenaar, RAEM

AU - Devilee, P

AU - Le Marchand, L

AU - Haiman, CA

AU - Mannermaa, A

AU - Kosma, VM

AU - Radice, P

AU - Peterlongo, P

AU - Marme, F

AU - Burwinkel, B

AU - van Deurzen, Carolien

AU - Hollestelle, Antoinette

AU - Miller, N

AU - Kerin, MJ

AU - Lambrechts, D

AU - Floris, G

AU - Wesseling, J

AU - Flyger, H

AU - Bojesen, SE

AU - Yao, S

AU - Ambrosone, CB

AU - Chenevix-Trench, G

AU - Truong, T

AU - Guenel, P

AU - Rudolph, A

AU - Chang-Claude, J

AU - Nevanlinna, H

AU - Blomqvist, C

AU - Czene, K

AU - Brand, JS

AU - Olson, JE

AU - Couch, FJ

AU - Dunning, AM

AU - Hall, P

AU - Easton, DF

AU - Pharoah, PDP

AU - Pinder, SE

AU - Schmidt, MK (Marjanka)

AU - Tomlinson, I

AU - Roylance, R

AU - Garcia-Closas, M

AU - Sawyer, EJ

PY - 2016

Y1 - 2016

N2 - Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

AB - Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

U2 - 10.1186/s13058-016-0675-7

DO - 10.1186/s13058-016-0675-7

M3 - Article

C2 - 26884359

SN - 1465-5411

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

ER -