Dataset Information

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.

SUBMITTER: Petridis C

PROVIDER: S-EPMC4756509 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Genetic predisposition to ductal carcinoma in situ of the breast.

Petridis Christos C Brook Mark N MN Shah Vandna V Kohut Kelly K Gorman Patricia P Caneppele Michele M Levi Dina D Papouli Efterpi E Orr Nick N Cox Angela A Cross Simon S SS Dos-Santos-Silva Isabel I Peto Julian J Swerdlow Anthony A Schoemaker Minouk J MJ Bolla Manjeet K MK Wang Qin Q Dennis Joe J Michailidou Kyriaki K Benitez Javier J González-Neira Anna A Tessier Daniel C DC Vincent Daniel D Li Jingmei J Figueroa Jonine J Kristensen Vessela V Borresen-Dale Anne-Lise AL Soucy Penny P Simard Jacques J Milne Roger L RL Giles Graham G GG Margolin Sara S Lindblom Annika A Brüning Thomas T Brauch Hiltrud H Southey Melissa C MC Hopper John L JL Dörk Thilo T Bogdanova Natalia V NV Kabisch Maria M Hamann Ute U Schmutzler Rita K RK Meindl Alfons A Brenner Hermann H Arndt Volker V Winqvist Robert R Pylkäs Katri K Fasching Peter A PA Beckmann Matthias W MW Lubinski Jan J Jakubowska Anna A Mulligan Anna Marie AM Andrulis Irene L IL Tollenaar Rob A E M RA Devilee Peter P Le Marchand Loic L Haiman Christopher A CA Mannermaa Arto A Kosma Veli-Matti VM Radice Paolo P Peterlongo Paolo P Marme Frederik F Burwinkel Barbara B van Deurzen Carolien H M CH Hollestelle Antoinette A Miller Nicola N Kerin Michael J MJ Lambrechts Diether D Floris Giuseppe G Wesseling Jelle J Flyger Henrik H Bojesen Stig E SE Yao Song S Ambrosone Christine B CB Chenevix-Trench Georgia G Truong Thérèse T Guénel Pascal P Rudolph Anja A Chang-Claude Jenny J Nevanlinna Heli H Blomqvist Carl C Czene Kamila K Brand Judith S JS Olson Janet E JE Couch Fergus J FJ Dunning Alison M AM Hall Per P Easton Douglas F DF Pharoah Paul D P PD Pinder Sarah E SE Schmidt Marjanka K MK Tomlinson Ian I Roylance Rebecca R García-Closas Montserrat M Sawyer Elinor J EJ

Breast cancer research : BCR 20160217 1

<h4>Background</h4>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.<h4>Methods</h4>To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising ...[more]

PMID: 26884359

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Project description:Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

Dataset Information

Genetic predisposition to ductal carcinoma in situ of the breast.

Background

Methods

Results

Conclusion

Publications

Genetic predisposition to ductal carcinoma in situ of the breast.

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