TY - JOUR

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

AU - Petridis, Christos

AU - Brook, Mark N

AU - Shah, Vandna

AU - Kohut, Kelly

AU - Gorman, Patricia

AU - Caneppele, Michele

AU - Levi, Dina

AU - Papouli, Efterpi

AU - Orr, Nick

AU - Cox, Angela

AU - Cross, Simon S

AU - Dos-Santos-Silva, Isabel

AU - Peto, Julian

AU - Swerdlow, Anthony

AU - Schoemaker, Minouk J

AU - Bolla, Manjeet K

AU - Wang, Q.

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - Benitez, Javier

AU - González-Neira, Anna

AU - Tessier, Daniel C

AU - Vincent, Daniel

AU - Li, Jingmei

AU - Figueroa, Jonine

AU - Kristensen, Vessela

AU - Borresen-Dale, Anne-Lise

AU - Soucy, Penny

AU - Simard, Jacques

AU - Milne, Roger L

AU - Giles, Graham G

AU - Margolin, Sara

AU - Lindblom, Annika

AU - Brüning, Thomas

AU - Brauch, Hiltrud

AU - Southey, Melissa C

AU - Hopper, John L

AU - Dörk, Thilo

AU - Bogdanova, Natalia V

AU - Kabisch, Maria

AU - Hamann, Ute

AU - Schmutzler, Rita K

AU - Meindl, Alfons

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Fasching, Peter A

AU - Beckmann, Matthias W

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Mulligan, Anna Marie

AU - Andrulis, Irene L

AU - Tollenaar, Rob A E M

AU - Devilee, Peter

AU - Le Marchand, Loic

AU - Haiman, Christopher A

AU - Mannermaa, Arto

AU - Kosma, Veli-Matti

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Marme, Frederik

AU - Burwinkel, Barbara

AU - van Deurzen, Carolien H M

AU - Hollestelle, Antoinette

AU - Miller, Nicola

AU - Kerin, Michael J

AU - Lambrechts, Diether

AU - Floris, Giuseppe

AU - Wesseling, Jelle

AU - Flyger, Henrik

AU - Bojesen, Stig E

AU - Yao, Song

AU - Ambrosone, Christine B

AU - Chenevix-Trench, Georgia

AU - Truong, Thérèse

AU - Guénel, Pascal

AU - Rudolph, Anja

AU - Chang-Claude, Jenny

AU - Nevanlinna, Heli

AU - Blomqvist, Carl

AU - Czene, Kamila

AU - Brand, Judith S

AU - Olson, Janet E

AU - Couch, Fergus J

AU - Dunning, Alison M

AU - Hall, Per

AU - Easton, Douglas F

AU - Pharoah, Paul D P

AU - Pinder, Sarah E

AU - Schmidt, Marjanka K

AU - Tomlinson, Ian

AU - Roylance, Rebecca

AU - García-Closas, Montserrat

AU - Sawyer, Elinor J

PY - 2016/2/17

Y1 - 2016/2/17

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 - Journal article

C2 - 26884359

VL - 18

SP - 1

EP - 15

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

M1 - 22

ER -