Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

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Date
2018-05-01ICR Author
Author
Painter, JN
O'Mara, TA
Morris, AP
Cheng, THT
Gorman, M
Martin, L
Hodson, S
Jones, A
Martin, NG
Gordon, S
Henders, AK
Attia, J
McEvoy, M
Holliday, EG
Scott, RJ
Webb, PM
Fasching, PA
Beckmann, MW
Ekici, AB
Hein, A
Rübner, M
Hall, P
Czene, K
Dörk, T
Dürst, M
Hillemanns, P
Runnebaum, I
Lambrechts, D
Amant, F
Annibali, D
Depreeuw, J
Vanderstichele, A
Goode, EL
Cunningham, JM
Dowdy, SC
Winham, SJ
Trovik, J
Hoivik, E
Werner, HMJ
Krakstad, C
Ashton, K
Otton, G
Proietto, T
Tham, E
Mints, M
Ahmed, S
Healey, CS
Shah, M
Pharoah, PDP
Dunning, AM
Dennis, J
Bolla, MK
Michailidou, K
Wang, Q
Tyrer, JP
Hopper, JL
Peto, J
Swerdlow, AJ
Burwinkel, B
Brenner, H
Meindl, A
Brauch, H
Lindblom, A
Chang-Claude, J
Couch, FJ
Giles, GG
Kristensen, VN
Cox, A
Zondervan, KT
Nyholt, DR
MacGregor, S
Montgomery, GW
Tomlinson, I
Easton, DF
Thompson, DJ
Spurdle, AB
Type
Journal Article
Metadata
Show full item recordAbstract
Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
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Subject
Endometrium
Humans
Endometrial Neoplasms
Endometriosis
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Australia
Female
STAT3 Transcription Factor
Receptor-Like Protein Tyrosine Phosphatases, Class 2
Genome-Wide Association Study
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2018-01-21
License start date
2018-05
Citation
Cancer medicine, 2018, 7 (5), pp. 1978 - 1987
Publisher
WILEY