Abstract
IntroductionBreast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.MethodsTo evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.ResultsWe found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11–1.38, P = 1.27 x 10−4) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99–1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09–1.42, P = 1.07 x 10−3). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.ConclusionsOur study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0596-x) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs
Ductal carcinoma in situ (DCIS) is known to be a different entity from lobular carcinoma in situ (LCIS), which is characterized by proliferation of malignant cells in the lobules of the breast [9] and is more frequently associated to lobular invasive BC than to ductal invasive BC
In this study, we investigated the possible effect of 39 single nucleotide polymorphism (SNP) associated with invasive BC on the susceptibility of BCIS using 1317 BCIS cases and 14,006 healthy controls in the framework of BPC3
Summary
Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Ductal carcinoma in situ (DCIS) is the most common form of noninvasive BC It is characterized by malignant epithelial cells inside the milk ducts of the breast. DCIS is known to be a different entity from lobular carcinoma in situ (LCIS), which is characterized by proliferation of malignant cells in the lobules of the breast [9] and is more frequently associated to lobular invasive BC than to ductal invasive BC. DCIS is generally considered a precursor lesion of invasive BC; a direct causality has not been firmly established because it is not possible to verify that the removal of DCIS decreases the risk of developing the invasive disease [3, 10]
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