Journal article
Polymorphisms in inflammation pathway genes and endometrial cancer risk
Cancer Epidemiology Biomarkers and Prevention, Vol.22(2), pp.216-223
2013
Abstract
Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. © 2012 American Association for Cancer Research.
Details
- Title
- Polymorphisms in inflammation pathway genes and endometrial cancer risk
- Authors
- R J Delahanty (Author) - Vanderbilt University School of Medicine, United StatesY B Xiang (Author) - Shanghai Cancer Institute, ChinaA Spurdle (Author) - Queensland Institute of Medical ResearchA Beeghly-Fadiel (Author) - Vanderbilt University School of Medicine, United StatesJ Long (Author) - Vanderbilt University School of Medicine, United StatesD Thompson (Author) - University of Cambridge, United KingdomI Tomlinson (Author) - University of Oxford, United KingdomH Yu (Author) - Yale University, United StatesD Lambrechts (Author) - Katholieke Universiteit Leuven, BelgiumT Dörk (Author) - Hannover Medical School, GermanyM T Goodman (Author) - University of Hawaii, United StatesY Zheng (Author) - Shanghai Institute of Preventive Medicine, ChinaH B Salvesen (Author) - University of Bergen, NorwayP P Bao (Author) - Shanghai Institute of Preventive Medicine, ChinaF Amant (Author) - Katholieke Universiteit Leuven, BelgiumM W Beckmann (Author) - University Hospital Erlangen, GermanyL Coenegrachts (Author) - Katholieke Universiteit Leuven, BelgiumA Coosemans (Author) - Katholieke Universiteit Leuven, BelgiumN Dubrowinskaja (Author) - Hannover Medical School, GermanyA Dunning (Author) - University of Oxford, United KingdomI B Runnebaum (Author) - Jena University Hospital, GermanyD Easton (Author) - University of Cambridge, United KingdomA B Ekici (Author) - University of California, United StatesP A Fasching (Author) - University of California, United StatesM K Halle (Author) - University of Bergen, NorwayA Hein (Author) - University Hospital Erlangen, GermanyK Howarth (Author) - University of Oxford, United KingdomM Gorman (Author) - University of Oxford, United KingdomD Kaydarova (Author) - State Oncology Institute, KazakhstanC Krakstad (Author) - University of Bergen, NorwayFelicity Lose (Author) - Queensland Institute of Medical ResearchL Lu (Author) - Yale University, United StatesG Lurie (Author) - University of Hawaii, United StatesT O'Mara (Author) - Queensland Institute of Medical ResearchR K Matsuno (Author) - University of Hawaii, United StatesP Pharoah (Author) - University of Cambridge, United KingdomH Risch (Author) - Yale University, United StatesM Corssen (Author) - Hannover Medical School, GermanyJ Trovik (Author) - University of Bergen, NorwayN Turmanov (Author) - Hannover Medical School, GermanyW Wen (Author) - Vanderbilt University School of Medicine, United StatesW Lu (Author) - Shanghai Institute of Preventive Medicine, ChinaQ Cai (Author) - Vanderbilt University School of Medicine, United StatesW Zheng (Author) - Vanderbilt University School of Medicine, United StatesX O Shu (Author) - Vanderbilt University School of Medicine, United States
- Publication details
- Cancer Epidemiology Biomarkers and Prevention, Vol.22(2), pp.216-223
- Publisher
- American Association for Cancer Research
- Date published
- 2013
- DOI
- 10.1158/1055-9965.EPI-12-0903
- ISSN
- 1055-9965
- Copyright note
- Copyright © 2013 The Authors. The accepted manuscript is reproduced in accordance with the copyright policy of the publisher. The final version is available at http://dx.doi.org/10.1158/1055-9965.EPI-12-0903
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of Research
- Language
- English
- Record Identifier
- 99450923002621
- Output Type
- Journal article
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