Association of Insulin Receptor Substrate-2 Gene Polymorphism with Ovarian Cancer

Yıl 2011, Cilt: 2011 Sayı: 1, 14 - 17, 01.01.2011

Filiz Çayan Ramazan Gen Nurcan Aras Ateş Lokman Ayaz Esen Akbay Saffet Dilek

https://doi.org/10.5174/tutfd.2009.03134.1

Öz

Objective: The insulin receptor substrate (IRS) proteins have been implicated in contributing to all stages of tumorigenesis in many cancers, from initiating events to metastatic progression. In this study, we aimed to evaluate the association of IRS-2 gene polymorphism with ovarian cancer. Material and Methods: The study group consisted of 185 women: 45 women with ovarian cancer and 140 control subjects. All the patients with ovarian cancer were primarily treated by surgical intervention. Genetic polymorphism of IRS-2 G1057D was detected by using polymerase chain reaction (PCR)- based restriction fragment-length polymorphism (RFLP). Results: For IRS-2 G1057D polymorphism, the frequencies of GG, GD and DD genotypes were 60%, 33.3%, and 6.7%, respectively in the ovarian cancer cases and 53.6%, 38.6% and 7.9 % in controls. The risk for ovarian cancer was not significantlydifferent in the individuals with the IRS-2 DD genotype compared to the GG genotype (95% CI: 0.203-3.04, P: 0.787). Also, there was no association between carriage of the D allele and ovarian cancer risk. We found no significant difference between the genotypes in the ovarian cancer group and control group (P:0.545). Conclusion: These results do not support an association between carriage of the G1057D variant of IRS-2 gene and ovarian cancer.

Anahtar Kelimeler

Insulin receptor substrate-2 gene polymorphism, ovarian cancer, G1057D variation

Association of Insulin Receptor Substrate-2 Gene Polymorphism with Ovarian Cancer

Öz

Kaynakça

• Dearth RK, Cui X, Kim HJ, Hadsell DL, Lee AV. Oncogenic trans- formation by the signaling adaptor proteins insulin receptor sub- strate (IRS)-1 and IRS-2. Cell Cycle 2007;6:705-13.
• Burks DJ, Font de Mora J, Schubert M, Withers DJ, Myers MG, Towery HH et al. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 2000;407:377-82.
• Slattery ML, Samowitz W, Curtin K, Ma KN, Hoffman M, Caan B et al. Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer. Cancer Epidemiol Bio- markers Prev 2004;13:1206-14.
• Gibson SL, Ma Z, Shaw LM. Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis. Cell Cycle 2007;6:631-7. [CrossRef]
• Neganova I, Al-Qassab H, Heffron H, Selman C, Choudhury AI, Lingard SJ et al. Role of central nervous system and ovarian insu- lin receptor substrate 2 signaling in female reproductive function in the mouse. Biol Reprod 2007;76:1045-53. [CrossRef]
• White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab 2002;283:413-22.
• Lautier C, El Mkadem SA, Renard E, Brun JF, Gris JC, Bringer J et al. Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mu- tation. Hum Genet 2003;113:34-43.
• Mammarella S, Romano F, Di Valerio A, Creati B, Esposito DL, Palmirotta R et al. Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes. Hum Mol Genet 2000;9:2517-21. [CrossRef]
• Rosen DG, Yang G, Liu G, Mercado-Uribe I, Chang B, Xiao XS et al. Ovarian cancer: pathology, biology, and disease models. Front Biosci 2009;14:2089-102.
• FIGO. Annual report on the results of treatment in gynecologic cancer. Int J Gynecol Obstet 1989;28:189-93.
• WHO classification of tumors, pathology and genetics, tumours of the breast and female genital organs. Eds: Tavassoli FA, Dev- ilee P. In Chapter 4, Tumors of the uterine corpus. pp: 218. IARC press, Lyon 2000.
• White MF. The IRS-signaling system: a network of docking pro- teins that mediate insulin and cytokine action. Recent Prog Horm Res 1998;53:119-38.
• White MF. The insulin signalling system and the IRS proteins. Dia- betologia 1997;40:2-17. [CrossRef]
• Yamauchi T, Kaburagi Y, Ueki K, Tsuji Y, Stark GR, Kerr IM et al. Growth hormone and prolactin stimulate tyrosine phosphoryla- tion of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and con- comitantly PI3-kinase activation via JAK2 kinase. J Biol Chem 1998;273:15719-26.
• Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM. Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol. 2004;24:9726-35. [CrossRef]
• Mardilovich K, Pankratz SL, Shaw LM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Commun Signal 2009;7:14. [CrossRef]
• Platanias LC, Uddin S, Yetter A, Sun XJ, White MF. The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2. J Biol Chem 1996;271:278-82. [CrossRef]
• Shaw LM. Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-de- pendent activation of phosphoinositide 3-OH kinase and promo- tion of invasion. Mol Cell Biol 2001;21:5082-93. [CrossRef]
• Khalili K, Del Valle L, Wang JY, Darbinian N, Lassak A, Safak M et al. T-antigen of human polyomavirus JC cooperates withIGF-IR signaling system in cerebellar tumors of the childhood-medullo- blastomas. Anticancer Res 2003;23:2035-41.
• Lannon CL, Martin MJ, Tognon CE, Jin W, Kim SJ, Sorensen PH. A highly conserved NTRK3 C-terminal sequence in the ETV6- NTRK3 oncoprotein binds the phosphotyrosine binding domain of insulin receptor substrate-1: an essential interaction for trans- formation. J Biol Chem 2004;279:6225-34.
• Chan BT, Lee AV. Insulin receptor substrates (IRSs) and breast tu- morigenesis. J Mammary Gland Biol Neoplasia. 2008;13:415-22. [CrossRef]
• Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X et al. Mammary tumorigenesis and metastasis caused by overexpres- sion of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol 2006;26:9302-14. [CrossRef]
• Bergmann U, Funatomi H, Kornmann M, Beger HG, Korc M. Increased expression of insulin receptor substrate-1 in human pancreatic cancer. Biochem Biophys Res Commun 1996;220:886-90. [CrossRef]
• Boissan M, Beurel E, Wendum D, Rey C, Lécluse Y, Housset C et al. Overexpression of insulin receptor substrate-2 in human and murine hepatocellular carcinoma. Am J Pathol 2005;167:869-77. [CrossRef]
• Neuhausen SL, Slattery ML, Garner CP, Ding YC, Hoffman M, Brothman AR. Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: strong association of IRS1 G972R variant and cancer risk. Prostate 2005;64:168-74. [CrossRef]