Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.

Authors:
Ms Maggie Gorman, RN
Ms Maggie Gorman, RN
Institute of Cancer Research
London | United Kingdom
Dr. Augusto Rojas-Martinez, M.D., DSc.
Dr. Augusto Rojas-Martinez, M.D., DSc.
School of Medicine / Tecnológico de Monterrey
Full-time professor and researcher
Human Genetics, Molecular Biology
MONTERREY, Nuevo León | Mexico
Angela Jones
Angela Jones
HudsonAlpha Institute for Biotechnology
Senior scientist
Huntsville, AL | United States

Sci Rep 2015 12 1;5:17369. Epub 2015 Dec 1.

Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

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.

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http://dx.doi.org/10.1038/srep17369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664893PMC
December 2015
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