Polymorphisms in inflammation pathway genes and endometrial cancer risk

Delahanty, R.J., Xiang, Y.-B., Spurdle, A., Beeghly-Fadiel, A., Long, J., Thompson, D., Tomlinson, I., Yu, H., Lambrechts, D., Dork, T., Goodman, M.T., Zheng, Y., Salvesen, H.B., Bao, P.-P., Amant, F., Beckmann, M.W., Coenegrachts, L., Coosemans, A., Dubrowinskaja, N., Dunning, A., Runnebaum, I.B., Easton, D., Ekici, A.B., Fasching, P.A., Halle, M.K., Hein, A., Howarth, K., Gorman, M., Kaydarova, D., Krakstad, C., Lose, F., Lu, L., Lurie, G., O'Mara, T., Matsuno, R.K., Pharoah, P., Risch, H., Corssen, M., Trovik, J., Turmanov, N., Wen, W., Lu, W., Cai, Q., Zheng, W. and Shu, X.-O. (2013) Polymorphisms in inflammation pathway genes and endometrial cancer risk. Cancer Epidemiology Biomarkers and Prevention, 22 2: 216-223. doi:10.1158/1055-9965.EPI-12-0903

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Author Delahanty, R.J.
Xiang, Y.-B.
Spurdle, A.
Beeghly-Fadiel, A.
Long, J.
Thompson, D.
Tomlinson, I.
Yu, H.
Lambrechts, D.
Dork, T.
Goodman, M.T.
Zheng, Y.
Salvesen, H.B.
Bao, P.-P.
Amant, F.
Beckmann, M.W.
Coenegrachts, L.
Coosemans, A.
Dubrowinskaja, N.
Dunning, A.
Runnebaum, I.B.
Easton, D.
Ekici, A.B.
Fasching, P.A.
Halle, M.K.
Hein, A.
Howarth, K.
Gorman, M.
Kaydarova, D.
Krakstad, C.
Lose, F.
Lu, L.
Lurie, G.
O'Mara, T.
Matsuno, R.K.
Pharoah, P.
Risch, H.
Corssen, M.
Trovik, J.
Turmanov, N.
Wen, W.
Lu, W.
Cai, Q.
Zheng, W.
Shu, X.-O.
Title Polymorphisms in inflammation pathway genes and endometrial cancer risk
Journal name Cancer Epidemiology Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
1538-7755
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-12-0903
Volume 22
Issue 2
Start page 216
End page 223
Total pages 8
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject 2713 Epidemiology
2730 Oncology
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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