Polymorphisms in inflammation pathway genes and endometrial cancer risk

Delahanty, Ryan J., Xiang, Yong-Bing, Spurdle, Amanda, Beeghly-Fadiel, Alicia, Long, Jirong, Thompson, Deborah, Tomlinson, Ian, Yu, Herbert, Lambrechts, Diether, Dork, Thilo, Goodman, Marc T., Zheng, Ying, Salvesen, Helga B., Bao, Ping-Ping, Amant, Frederic, Beckmann, Matthias W., Coenegrachts, Lieve, Coosemans, An, Dubrowinskaja, Natalia, Dunning, Alison, Runnebaum, Ingo B., Easton, Douglas, Ekici, Arif B., Fasching, Peter A., Halle, Mari K., Hein, Alexander, Howarth, Kimberly, Gorman, Maggie, Kaydarova, Dylyara, Krakstad, Camilla, Lose, Felicity, Lu, Lingeng, Lurie, Galina, O'Mara, Tracy, Matsuno, Rayna K., Pharoah, Paul, Risch, Harvey, Corssen, Madeleine, Trovik, Jone, Turmanov, Nurzhan, Wen, Wanqing, Lu, Wei, Cai, Qiuyin, Zheng, Wei, & Shu, Xiao-Ou (2013) Polymorphisms in inflammation pathway genes and endometrial cancer risk. Cancer Epidemiology, Biomarkers and Prevention, 22(2), pp. 216-223.

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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.

Impact and interest:

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ID Code: 68359
Item Type: Journal Article
Refereed: Yes
Keywords: endometrial cancer, inflammation, genetic risk variants, meta-analysis
DOI: 10.1158/1055-9965.EPI-12-0903
ISSN: 1538-7755
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 American Association for Cancer Research.
Deposited On: 12 Mar 2014 23:00
Last Modified: 14 Mar 2014 06:23

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