Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
Author(s)
Type
Journal Article
Abstract
High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
Date Issued
2015-12-01
Date Acceptance
2015-10-28
Citation
Scientific Reports, 2015, 5
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
5
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MICROSATELLITE INSTABILITY
DNA-POLYMERASE
LYNCH-SYNDROME
BREAST-CANCER
MTHFR C677T
RISK
LOCI
VARIANTS
MUTATIONS
CARCINOMA
Humans
Colorectal Neoplasms
Endometrial Neoplasms
Genetic Predisposition to Disease
Proteins
Homeodomain Proteins
Neoplasm Proteins
Polymorphism, Genetic
Alleles
Female
Male
Genome-Wide Association Study
Publication Status
Published
Article Number
17369