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. 2016 Feb 17;18(1):22.
doi: 10.1186/s13058-016-0675-7.

Genetic predisposition to ductal carcinoma in situ of the breast

Christos Petridis  1   2 , Mark N Brook  3 , Vandna Shah  4 , Kelly Kohut  5 , Patricia Gorman  6 , Michele Caneppele  7 , Dina Levi  8 , Efterpi Papouli  9 , Nick Orr  10 , Angela Cox  11 , Simon S Cross  12 , Isabel Dos-Santos-Silva  13 , Julian Peto  14 , Anthony Swerdlow  15   16 , Minouk J Schoemaker  17 , Manjeet K Bolla  18 , Qin Wang  19 , Joe Dennis  20 , Kyriaki Michailidou  21 , Javier Benitez  22   23 , Anna González-Neira  24 , Daniel C Tessier  25 , Daniel Vincent  26 , Jingmei Li  27 , Jonine Figueroa  28 , Vessela Kristensen  29   30   31 , Anne-Lise Borresen-Dale  32   33 , Penny Soucy  34 , Jacques Simard  35 , Roger L Milne  36   37 , Graham G Giles  38   39 , Sara Margolin  40 , Annika Lindblom  41 , Thomas Brüning  42 , Hiltrud Brauch  43   44   45 , Melissa C Southey  46 , John L Hopper  47 , Thilo Dörk  48 , Natalia V Bogdanova  49 , Maria Kabisch  50 , Ute Hamann  51 , Rita K Schmutzler  52   53   54 , Alfons Meindl  55 , Hermann Brenner  56   57   58 , Volker Arndt  59 , Robert Winqvist  60   61 , Katri Pylkäs  62   63 , Peter A Fasching  64   65 , Matthias W Beckmann  66 , Jan Lubinski  67 , Anna Jakubowska  68 , Anna Marie Mulligan  69   70 , Irene L Andrulis  71   72 , Rob A E M Tollenaar  73 , Peter Devilee  74   75 , Loic Le Marchand  76 , Christopher A Haiman  77 , Arto Mannermaa  78   79   80 , Veli-Matti Kosma  81   82   83 , Paolo Radice  84 , Paolo Peterlongo  85 , Frederik Marme  86   87 , Barbara Burwinkel  88   89 , Carolien H M van Deurzen  90 , Antoinette Hollestelle  91 , Nicola Miller  92 , Michael J Kerin  93 , Diether Lambrechts  94   95 , Giuseppe Floris  96 , Jelle Wesseling  97 , Henrik Flyger  98 , Stig E Bojesen  99   100   101 , Song Yao  102 , Christine B Ambrosone  103 , Georgia Chenevix-Trench  104 , Thérèse Truong  105   106 , Pascal Guénel  107   108 , Anja Rudolph  109 , Jenny Chang-Claude  110 , Heli Nevanlinna  111 , Carl Blomqvist  112 , Kamila Czene  113 , Judith S Brand  114 , Janet E Olson  115 , Fergus J Couch  116 , Alison M Dunning  117 , Per Hall  118 , Douglas F Easton  119   120 , Paul D P Pharoah  121   122 , Sarah E Pinder  123 , Marjanka K Schmidt  124 , Ian Tomlinson  125 , Rebecca Roylance  126 , Montserrat García-Closas  127   128 , Elinor J Sawyer  129
Affiliations

Genetic predisposition to ductal carcinoma in situ of the breast

Christos Petridis et al. Breast Cancer Res. .

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.

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Figures

Fig. 1
Fig. 1
Known breast cancer predisposition loci for ductal carcinoma in situ plotted according to the risk allele for invasive disease. Odds ratios >1 indicate that the association is in the same direction as previously published for invasive breast cancer
Fig. 2
Fig. 2
Known breast cancer predisposition loci for estrogen receptor-positive (ER+) (black lines) and ER– ductal carcinoma in situ (gray lines). Due to the large number of single nucleotide polymorphisms (SNPs), for better visual representation the plot is split into two different sections (a and b) with a descending order of effect size for the ER+ group. OR odds ratio
Fig. 3
Fig. 3
Known breast cancer predisposition loci for estrogen receptor-positive (ER+) (black) ductal carcinoma in situ and lobular carcinoma in situ (gray). Due to the large number of single nucleotide polymorphisms (SNPs), for better visual representation, the plot is split into two different sections (a and b) with a descending order of effect size for the ER+ group. OR odds ratio
See this image and copyright information in PMC

Comment in

References

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