Steven A. Narod

Victoria Sopik

PubMed

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Common genetic susceptibility to DCIS and invasive ductal carcinoma

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LETTER Open Access
Common genetic susceptibility to DCIS
and invasive ductal carcinoma
Victoria Sopik and Steven A. Narod*
See related research by Petridis et al., http://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-016-0675-7
In a recent issue of Breast Cancer Research, Petridis and
colleagues report a failure to detect any genetic poly-
morphism which predisposes to ductal carcinoma in situ
(DCIS) but not to invasive ductal carcinoma (IDC) or
vice versa [1]. They genotyped 5067 cases of DCIS,
24,584 cases of IDC, and 37,467 non-cancer controls for
76 different single nucleotide polymorphisms (SNPs),
each of which has been shown to be associated with
breast cancer susceptibility in previous studies [2, 3].
They found no significant difference in the magnitude of
the associations for DCIS and IDC for any of the 76 loci.
From this, the authors conclude that the genes respon-
sible for DCIS and IDC are, by and large, the same and
that larger studies are required to determine if suscepti-
bility loci specific to DCIS exist.
The authors base the rationale for this study on
the premise that DCIS and IDC are distinct
pathologies, in that DCIS is non-invasive and is a
non-obligate ‘precursor’ lesion. Accordingly, they
seek a biological basis which helps underpin the dis-
tinction. A simpler and parsimonious explanation for
the overlap in gene sets is that DCIS and IDC repre-
sent various phases of the same disease process, ra-
ther than distinct forms of cancer, as we have
recently proposed [4]. In this sense, it is unlikely
that they will identify genes which predispose to
stage 0 but not to stage I breast cancer (as one
would not expect to find genes that predispose to
stage II but not stage I cancer). If one wishes to
study the possibility that host factors are associated
with cancer stage at presentation—and with rate of
progression—it is better to study breast cancers in
their entire range (from stage 0 to stage IV) and to
look for overall trends in prevalence.
Authors’ response
Christos Petridis, Sarah E. Pinder, Ian Tomlinson, Rebecca Roylance and Elinor J. Sawyer
In response to the comments by Sopik and Narod we
would like to point out that the premise of our study
was not that DCIS and IDC are distinct pathologies and
we were not therefore seeking a biological basis to
explain this distinction. Indeed we state that: “45–78 %
of all invasive breast cancers are associated with DCIS
and it is hypothesized in the majority of these cases that
the invasive component has arisen from the DCIS as
they generally share the same somatic genetic changes”
[1]. We agree with the obvious explanation, which is that
DCIS and IDC represent various phases of the same
disease process.
Nevertheless, it is also clear that not all DCIS pro-
gresses to an invasive lesion. In particular, there are
concerns regarding over-diagnosis and over-treatment of
DCIS through screening programmes [5]. Current
methods for accurately predicting the behaviour of an
individual DCIS lesion are poor, with many researchers
attempting to identify molecular biomarkers that can be
used to distinguish between aggressive and non-
aggressive DCIS with, to date, little success. The ration-
ale for our study was to ascertain whether a subgroup of
non-aggressive DCIS could be identified by examining
low-risk genetic susceptibility loci, rather than looking at
somatic changes within DCIS.
In our study we examined the extent to which DCIS
without associated invasive disease (5067 cases) and IDC
(24,584 cases) share low-risk susceptibility loci and
* Correspondence: steven.narod@wchospital.ca
Women’s College Research Institute, 76 Grenville Street, Toronto, Ontario,
Canada
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sopik and Narod Breast Cancer Research  (2016) 18:60 
DOI 10.1186/s13058-016-0719-z
whether there were any differences in the strength of the
associations. We found no differences, although there
were some DCIS-specific loci that did not reach
genome-wide significance. Therefore, our data largely
support the theory that DCIS and IDC are, in fact, a
continuum of the same disease, but we cannot exclude
the possibility that there may be some low-risk suscepti-
bility loci that have a strong association with stage 0 and
a weaker association with stage I breast cancer. Identify-
ing any such loci is important as it would identify a
subset of DCIS that has a low risk of progression.
Abbreviations
DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; SNP, single
nucleotide polymorphism
Funding
The authors have no sources of funding to declare.
Authors’ contributions
VS and SAN made equal contributions to the conception and design of the
letter, drafting the letter, and revising it critically for important intellectual
content. Both authors read and approved the final manuscript.
Competing interests
The authors have no competing interests to declare.
Received: 28 April 2016 Accepted: 29 April 2016
References
1. Petridis C, Brook MN, Shah V, Kohut K, Gorman P, Caneppele M, et al.
Genetic predisposition to ductal carcinoma in situ of the breast. Breast
Cancer Res. 2016;18(1):22.
2. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RC,
et al. Large-scale genotyping identifies 41 new loci associated with breast
cancer risk. Nat Genet. 2013;45(4):353–61.
3. Milne RL, Burwinkel B, Michailidou K, Arias-Perez J, Zamora MP, Menendez-
Rodriquez P, et al. Common non-synonymous SNPs associated with breast
cancer susceptibility: findings from the Breast Cancer Association
Consortium. Hum Mol Genet. 2014;23(22):6096–111.
4. Sopik V, Nofechs-Mozes S, Sun P, Narod SA. The relationship between local
recurrence and death in early-stage breast cancer. Breast Cancer Res Treat.
2016;155(1):175–85.
5. Narod S. Breast cancer: The importance of overdiagnosis in breast-cancer
screening. Nat Rev Clin Oncol. 2016;13(1):5–6.
Sopik and Narod Breast Cancer Research  (2016) 18:60 Page 2 of 2


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Common genetic susceptibility to DCIS and invasive ductal carcinoma

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