| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Departments of Obstetrics and Gynecology, University of Vienna Medical School, A-1090 Vienna, Austria [L. A. H., C. G., A. R. R-R., S. L., R. Z., C. B. T.]; Friedrich-Alexander-University Erlangen, Nuernberg, Germany [L. A. H., S. A., S. M., M. W. B.]; and Martin-Luther-University Halle, Wittenberg, Germany [H. K.]
| ABSTRACT |
|---|
|
|
|---|
| Introduction |
|---|
|
|
|---|
With respect to ovarian cancer, in vitro experiments have shown that various ovarian carcinoma cell lines produce IL-6, which is thought to be involved in ovarian carcinogenesis by mediating host immune responses to the disease (2, 3, 4) . In humans, IL-6 levels in ascitic fluid were found to be significantly elevated in patients with ovarian cancer compared with controls (5) . Ascitic IL-6 levels were also associated with peripheral CRP levels, which are thought to serve as additional prognostic parameters by themselves (6 , 7) . Furthermore, IL-6 serum levels have been associated with an increased tumor burden and impaired survival (8, 9, 10) . A possible use as additional tumor marker of serum IL-6 has been suggested.
The human IL-6 gene (IL-6) is mapped to chromosome 7p2124 with an upstream promoter containing 303 bp (11) . A common G/C polymorphism of the IL-6 promoter on position -174 has been investigated in a wide variety of diseases, including multiple myeloma, coronary heart disease, and endometriosis (12 , 13) . Of note, the -174 C IL6 polymorphism has been shown to influence in vivo protein expression (6 , 14) .
Thus, based on the important role of IL-6 in ovarian carcinogenesis, IL-6 can be regarded as a candidate gene for ovarian cancer. In the present study, we hypothesized that the -174 C IL6 polymorphism is associated with the biological phenotype of ovarian cancer.
| Materials and Methods |
|---|
|
|
|---|
Median age at the time of diagnosis of ovarian cancer was 54 (range 2686) years. Histologically, 67 tumors were graded as serous adenocarcinomas, 25 as mucinous adenocarcinomas, 25 as endometrioid adenocarcinomas, 9 as clear cell carcinomas, and 4 as undifferentiated carcinomas. Thirty-one tumors were graded as well differentiated, 34 as moderately differentiated, and 56 as poorly differentiated. The median (range) duration of follow-up was 38.1 (4163) months. Forty-four patients developed recurrent disease; 23 patients died of cancer-related death during the observation period. CA 125 and CRP serum levels were evaluated before surgery. Patients were treated and followed up according to established protocols.
Genotyping.
Pyrosequencing was performed according to established protocols as described previously (15)
. CA 125 and CRP serum levels were measured before surgery in all patients.
Statistics.
Where appropriate,
2 analysis was performed. Odds ratios and 95% confidence intervals are given accordingly. Survival probabilities were calculated by the product limit method of Kaplan and Meier using the Log-rank test. The results were analyzed for the end point of DFS and OS. Survival times of patients still alive were censored with the last follow-up date. A multivariate Cox regression model was performed comprising tumor stage, lymph node involvement, residual tumor mass, and -174 C IL6 polymorphism. Ps < 0.05 were considered statistically significant. For statistical analysis, we used the SPSS statistical software system (SPSS 11.0; SPSS, Inc., Chicago, IL).
| Results and Discussion |
|---|
|
|
|---|
|
|
|
|
The number of genetic association studies in all fields of medicine has risen substantially in recent years. Testing of mutations and polymorphisms in candidate genes of ovarian cancer revealed a close association between the risk for and survival length of ovarian cancer and BRCA1, BRCA2, p53, and nm23-H1 (16, 17, 18) . As published previously for breast cancer, microarray techniques allowing for the simultaneous detection of a high number of polymorphism might provide prognostic information in addition to established clinical parameters (19) . In our present study, we ascertained a significant association between the presence of the mutant -174 C allele and early tumor stage. In addition, carriage of the mutant -174 C allele was associated with improved DFS and OS in a univariate and multivariate regression model. Of note, the -174C IL6 polymorphism was the best predictor of DFS in this model. Our data support the assumption that IL-6, most likely via host-immune response modification, is involved in local tumor growth and prognosis of ovarian cancer.
Overall, it can be stated that the -174 G/C promoter polymorphism of IL-6 influences the biological phenotype of ovarian cancer. These data confirm IL-6 as a candidate gene for ovarian cancer and suggest that the -174G/C polymorphism of IL6 should be included in future analyses of the genetic background of this disease.
| FOOTNOTES |
|---|
1 To whom requests for reprints should be addressed, at Department of Obstetrics and Gynecology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Phone: 43 1 40400 2962; Fax: 43 1 40400 2911; E-mail: lukas.hefler{at}akh-wien.ac.at ![]()
2 The abbreviations used are: IL, interleukin; CRP, C-reactive protein; OS, overall survival; DFS, disease-free survival. ![]()
Received 2/ 8/03. Accepted 5/ 1/03.
| REFERENCES |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
S. Wilkening, B. Tavelin, F. Canzian, K. Enquist, R. Palmqvist, A. Altieri, G. Hallmans, K. Hemminki, P. Lenner, and A. Forsti Interleukin promoter polymorphisms and prognosis in colorectal cancer Carcinogenesis, June 1, 2008; 29(6): 1202 - 1206. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Song, E. Hogdall, S. J. Ramus, R. A. DiCioccio, C. Hogdall, L. Quaye, V. McGuire, A. S. Whittemore, M. Shah, D. Greenberg, et al. Effects of Common Germ-Line Genetic Variation in Cell Cycle Genes on Ovarian Cancer Survival Clin. Cancer Res., February 15, 2008; 14(4): 1090 - 1095. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Hefler, A. Mustea, D. Konsgen, N. Concin, B. Tanner, R. Strick, G. Heinze, C. Grimm, E. Schuster, C. Tempfer, et al. Vascular Endothelial Growth Factor Gene Polymorphisms Are Associated with Prognosis in Ovarian Cancer Clin. Cancer Res., February 1, 2007; 13(3): 898 - 901. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Wrensch, A. McMillan, J. Wiencke, J. Wiemels, K. Kelsey, J. Patoka, H. Jones, V. Carlton, R. Miike, J. Sison, et al. Nonsynonymous Coding Single-Nucleotide Polymorphisms Spanning the Genome in Relation to Glioblastoma Survival and Age at Diagnosis Clin. Cancer Res., January 1, 2007; 13(1): 197 - 205. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Grimm, L. Six, C. Tomovski, P. Speiser, E. Joura, R. Zeillinger, G. Sliutz, A. Reinthaller, and L. A. Hefler A Common Interleukin-6 Promoter Polymorphism in Patients With Vulvar Cancer Reproductive Sciences, December 1, 2005; 12(8): 617 - 620. [Abstract] [PDF] |
||||
![]() |
D. Leibovici, H. B. Grossman, C. P. Dinney, R. E. Millikan, S. Lerner, Y. Wang, J. Gu, Q. Dong, and X. Wu Polymorphisms in Inflammation Genes and Bladder Cancer: From Initiation to Recurrence, Progression, and Survival J. Clin. Oncol., August 20, 2005; 23(24): 5746 - 5756. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bhanoori, K. A. Babu, M. Deenadayal, S. Kennedy, and S. Shivaji The Interleukin-6 -174G/C Promoter Polymorphism Is Not Associated With Endometriosis in South Indian Women Reproductive Sciences, July 1, 2005; 12(5): 365 - 369. [Abstract] [PDF] |
||||
![]() |
M.J. BISSELL, P.A. KENNY, and D.C. RADISKY Microenvironmental Regulators of Tissue Structure and Function Also Regulate Tumor Induction and Progression: The Role of Extracellular Matrix and Its Degrading Enzymes Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 343 - 356. [Abstract] [PDF] |
||||
![]() |
A. Huber, C. Grimm, S. Jirecek, R. Zeillinger, K. Heim, P. Husslein, and L. Hefler An lnterleukin-6 Gene Promoter Polymorphism and Unexplained Late Intrauterine Fetal Death: A Multicenter Study Reproductive Sciences, January 1, 2005; 12(1): 33 - 36. [Abstract] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |