OJGas  Vol.2 No.2 , May 2012
STAT1 gene mutation is not implicated in upper aerodigestive cancers
ABSTRACT
Autosomal Dominant Chronic Mucocutaneous Candidiasis (AD-CMC) is characterized by defective T cell immunity, leading to fungal infections limited to mucosal surfaces. Recently it was discovered that mutations in the coiled-coil (CC) domain of STAT1 are the cause of AD-CMC. STAT1 deficiency has been implicated in experimental models of oesophageal cancer (EC) and head and neck carcinoma (HNC). Both carcinoma types are prevalent among CMC patients. Consequently, we postulated that the same mutation in the STAT1 gene triggering AD-CMC, could also be involved in oesophageal- or head and neck carcinogenesis. However we failed to identify the c.820C>T mutation in the STAT1 CC domain in 3 cohorts of Dutch Caucasian origin: being 351 EC patients, 325 HNC patients and 309 controls. Although it seems valuable to investigate the relationship between AD-CMC and upper aerodigestive neo- plasms, the c.820C>T mutation in the STAT1 gene does not seem implicated in EC and HNC aetiology.

Cite this paper
Dura, P. , Morsche, R. , Lacko, M. , Netea, M. , Meer, J. , Drenth, J. and Peters, W. (2012) STAT1 gene mutation is not implicated in upper aerodigestive cancers. Open Journal of Gastroenterology, 2, 68-71. doi: 10.4236/ojgas.2012.22014.
References
[1]   Adamkova, L., Souckova, K. and Kovarik, J. (2007) Transcription protein STAT1: Biology and relation to cancer. Folia Biologica, 53, 1-6.

[2]   Yang, J. and Stark, G.R. (2008) Roles of unphosphorylated STATs in signaling. Cell Research, 18, 443-451. doi:10.1038/cr.2008.41

[3]   Bowman, T., Garcia, R., Turkson, J. and Jove, R. (2000) STATs in oncogenesis. Oncogene, 19, 2474-2488. doi:10.1038/sj.onc.1203527

[4]   Nishibori, T., Tanabe, Y., Su, L. and David, M. (2004) Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: Increased susceptibility to autoimmune disease. Journal of Experimental Medicine, 199, 25-34. doi:10.1084/jem.20020509

[5]   van de Veerdonk, F.L., Plantinga, T.S., Hoischen, A., Smeekens, S.P., Joosten, L.A., Gilissen, C., et al. (2011) STAT1 Mutations in Autosomal Dominant Chronic Mucocutaneous Candidiasis. New England Journal of Medicine, 365, 54-61. doi:10.1056/NEJMoa1100102

[6]   Koch, D., Lilic, D. and Carmichael, A.J. (2009) Autosomal dominant chronic mucocu-taneous candidiasis and primary hypothyroidism complicated by oesophageal carcinoma. Clinical and Experimental Dermatology, 34, 818-820. doi:10.1111/j.1365-2230.2009.03561.x

[7]   Bjorses, P., Halonen, M., Palvimo, J.J., Kolmer, M., Aaltonen, J., Ellonen, P., et al. (2000) Mutations in the AIRE gene: Effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. American Journal of Human Genetics, 66, 378-392. doi:10.1086/302765

[8]   Watanabe, G., Kaganoi, J., Imamura, M., Shimada, Y., Itami, A., Uchida, S., et al. (2001) Progression of esophageal carcinoma by loss of EGF-STAT1 pathway. Cancer Journal, 7, 132-139.

[9]   Shim, S.H., Sung, M.W., Park, S.W. and Heo, D.S. (2009) Absence of STAT1 disturbs the anticancer effect induced by STAT3 inhibition in head and neck carcinoma cell lines. International Journal of Molecular Medicine, 23, 805-810.

[10]   Firth, N.A., O’Grady, J.F. and Reade, P.C. (1997) Oral squamous cell carcinoma in a young person with candidosis endocrinopathy syndrome: A case report. International Journal of Oral and Maxillofacial Surgery, 26, 42-44. doi:10.1016/S0901-5027(97)80845-4

[11]   Kristinsson, J.O., Van Westerveld, P., Te Morsche, R.H.M., Roelofs, H.M.J., Wobbes, T., Witteman, B.J., et al. (2009) Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma. World Journal of Gastroenterology, 15, 3493-3497. doi:10.3748/wjg.15.3493

[12]   Lacko, M., Roelofs, H.M.J., Te Morsche, R.H.M., Voogd, A.C., Oude Ophuis, M.B., Peters, W.H.M., et al. (2010) Genetic polymorphism in the conjugating enzyme UGT1A1 and the risk of head and neck cancer. International Journal of Cancer, 127, 2815-2821. doi:10.1002/ijc.25296

[13]   Bockle, B.C., Wilhelm, M., Muller, H., Gotsch, C. and Sepp, N.T. (2010) Oral mucous squamous cell carcinoma—an anticipated consequence of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APE- CED). Journal of the American Academy of Dermatology, 62, 864-868. doi:10.1016/j.jaad.2009.06.061

[14]   Rosa, D.D., Pasqualotto, A.C. and Denning, D.W. (2008) Chronic mucocutaneous candidiasis and oesophageal cancer. Medical Mycology, 46, 85-91. doi:10.1080/13693780701616023

[15]   Kalfa, V.C., Roberts, R.L. and Stiehm, E.R. (2003) The syndrome of chronic mucocutaneous candidiasis with selective antibody deficiency. Annals of Allergy Asthma and Immunology, 90, 259-264. doi:10.1016/S1081-1206(10)62152-7

[16]   Joshi, N., Johnson, L.L., Wei, W.Q., Abnet, C.C., Dong, Z.W., Taylor, P.R., et al. (2006) Gene expression differences in normal esophageal mucosa associated with regression and progression of mild and moderate squamous dysplasia in a high-risk Chinese population. Cancer Research, 66, 6851-6860. doi:10.1158/0008-5472.CAN-06-0662

[17]   Kaganoi, J., Watanabe, G., Okabe, M., Nagatani, S., Kawabe, A., Shimada, Y., et al. (2007) STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in vivo. Annals Surgical Oncology, 14, 1405-1415. doi:10.1245/s10434-006-9274-7

[18]   Ichiba, M., Miyazaki, Y., Kitamura, S., Kiyohara, T., Shinomura, Y. and Matsuzawa, Y. (2002) Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1. Journal of Gastroenterology, 37, 497-503. doi:10.1007/s005350200077

[19]   Laimer, K., Spizzo, G., Obrist, P., Gastl, G., Brunhuber, T., Schafer, G., et al. (2007) STAT1 activation in squamous cell cancer of the oral cavity: A potential predictive marker of response to adjuvant chemotherapy. Cancer, 110, 326-333. doi:10.1002/cncr.22813

[20]   Nikitakis, N.G., Siavash, H. and Sauk, J.J. (2004) Targeting the STAT pathway in head and neck cancer: Recent advances and future prospects. Current Cancer Drug Targets, 4, 637-651. doi:10.2174/1568009043332736

 
 
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