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Androgen receptor polyglutamine tract length in Egyptian male breast cancer patients

  • Epidemiology
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Abstract

Male Breast Cancer (MBC) is a rare disease in the U.S., accounting for less than 1% of all breast cancers. Rates of MBC in Africa are more variable than in the U.S., therefore, understanding the risk factors involved in a population like Egypt can clarify the nature of MBC. The polyglutamine tract (QT) is a variable region of the androgen receptor (AR), a nuclear receptor which is important in modulating androgen actions and generally inhibits growth in breast tissue. It is hypothesized that a long QT results in weaker AR activity over the lifetime, resulting in less AR mediated control over cellular division and higher risk of MBC. As a corollary, we expect to see a distribution skewed toward longer QTs in MBC patients compared to controls and overall relatively longer QT’s in populations with higher rates of MBC. This study aimed to investigate for the first time the distribution of AR QT lengths among MBC patients in Egypt. Paraffin-embedded tumor tissues from 44 Egyptian MBC patients were analyzed for this polymorphism. Amplification followed by fragment length analysis revealed QT length. For the control series, blood from 43 Egyptian males without a family or personal history of breast or prostate cancers was collected and analyzed similarly. There was no significant difference between patients and controls with respect to mean QT length (P = 0.84; means were 19.5 ± 2.8 and 19.3 ± 4.2, for patients and controls, respectively). Though, short QT lengths were more prevalent among controls (14.0%), but almost absent in cases (2.3%). Although the mean lengths were not different in cases and controls, the near absence of short tracts in cases suggests a possible protective effect of very short QT lengths against MBC. In populations in which there is variable incidence of MBC by region, investigations of the distribution of AR QT lengths are warranted to further delineate its role as a risk factor in MBC.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300. doi:10.3322/caac.20073

    Article  PubMed  Google Scholar 

  2. Freedman L, Edwards BK, Ries LAG, Al-Kayed S, Barchana M, Ibrahim AS, Komodiki C, Young JL (2006) Overview and summary data. In: Freedman LS, Edwards BK, Ries LAG, Young JL (eds) Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER, NIH Pub. No. 06-5873, Bethesda, MD, pp 1–27

  3. Incidence Des Cancer a Rabat, 2005 (2009) Cancer du Sein. Rabat, Morocco, pp 45–47

  4. Burson AM, Soliman AS, Ngoma TA, Mwaiselage J, Ogweyo P, Eissa MS, Dey S, Merajver SD (2010) Clinical and epidemiologic profile of breast cancer in Tanzania. Breast Dis. doi: 10.3233/BD-2009-0296

  5. Oguntola AS, Aderonmu AO, Adeoti ML, Olatoke SA, Akanbi O, Agodirin SO (2009) Male breast cancer in LAUTECH teaching hospital Osogbo, South Western Nigeria. Niger Postgrad Med J 16:166–170

    PubMed  CAS  Google Scholar 

  6. El-Gazayerli MM, Abdel-Aziz AS (1963) On bilharziasis and male breast cancer in Egypt: a preliminary report and review of the literature. Br J Cancer 17:566–571

    Article  PubMed  CAS  Google Scholar 

  7. Rennert G (2006) Breast cancer. In: Freedman LS, Edwards BK, Ries LAG, Young JL (eds) Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER, NIH Pub. No. 06-5873, Bethesda, MD, pp 73–79

  8. Soliman AS, Bondy ML, Raouf AA, Makram MA, Johnston DA, Levin B (1999) Cancer mortality in Menofeia, Egypt: comparison with US mortality rates. Cancer Causes Control 10:349–354. doi:10.1023/A:1008968701313

    Article  PubMed  CAS  Google Scholar 

  9. Barakat R, Farghaly A, El Masry AG, El-Sayed MK, Hussein MH (2000) The epidemiology of Schistosomiasis in Egypt: patterns of Schistosoma mansoni infection and morbidity in Kafer el-Sheikh. Am J Trop Med Hyg 62:21–27

    PubMed  CAS  Google Scholar 

  10. Michelson MK, Azziz FA, Gamil FM, Wahid AA, Richards FO, Juranek DD, Habib MA, Spencer HC (1993) Recent trends in the prevalence and distribution of Schistosomiasis in the Nile delta region. Am J Trop Med Hyg 49:76–87

    PubMed  CAS  Google Scholar 

  11. Anwar WA, Khaled HM, Amra HA, El-Nezami H, Loffredo CA (2008) Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res 659:176–184. doi:10.1016/j.mrrev.2008.01.005

    Article  PubMed  CAS  Google Scholar 

  12. El-Khoby T, Galal N, Fenwick A, Barakat R, El-Hawey A, Nooman Z, Habib M, Abdel-Wahab F, Gabr NS, Hammam HM, Hussein MH, Mikhail NN, Cline BL, Strickland GT (2000) The epidemiology of Schistosomiasis in Egypt: summary findings in nine governorates. Am J Trop Med Hyg 62:88–99

    PubMed  CAS  Google Scholar 

  13. Sherif M, Ibrahim AS, El-Aaser AA (1980) Prostatic carcinoma in Egypt: epidemiology and etiology. Scand J Urol Nephrol 55:25–26

    CAS  Google Scholar 

  14. Gouda I, Mokhtar N, Bilal D, El-Bolkainy T, El-Bolkainy NM (2007) Bilharziasis and bladder cancer: a time trend analysis of 9843 patients. J Egypt Natl Cancer Inst 19:158–162

    Google Scholar 

  15. Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J (1998) Risk of breast cancer in men with liver cirrhosis. Am J Gastroenterol 93:231–233. doi:10.1111/j.1572-0241.1998.00231.x

    PubMed  CAS  Google Scholar 

  16. Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G (2010) Etiologic factors for male breast cancer in the U.S. Veterans affairs medical care system database. Breast Cancer Res Treat 119:185–192. doi:10.1007/s10549-009-0379-0

    Article  PubMed  Google Scholar 

  17. Dey S, Zhang Z, Hablas A, Seifeldein IA, Ramadan M, El-Hamzawy H, Soliman AS (2010) Geographic patterns of cancer in the population-based registry of Egypt: possible links to environmental exposures. Cancer Epidemiol. doi:10.1016/j.canep.2010.09.010

  18. Khatib O, Aljurf M (2008) Cancer prevention and control in the eastern Mediterranean region: the need for a public health approach. Hematol Oncol Stem Cell Ther 1:44–52

    PubMed  Google Scholar 

  19. Rosenblatt KA, Thomas DB, McTiernan A, Austin MA, Stalsberg H, Stemhagen A, Thompson WD, Curnen MG, Satariano W, Austin DF (1991) Breast cancer in men: aspects of familial aggregation. J Natl Cancer Inst 83:849–854. doi:10.1093/jnci/83.12.849

    Article  PubMed  CAS  Google Scholar 

  20. Haraldsson K, Loman N, Zhang QX, Johannsson O, Olsson H, Borg A (1998) BRCA2 germ-line mutations are frequent in male breast cancer patients without a family history of the disease. Cancer Res 58:1367–1371

    PubMed  CAS  Google Scholar 

  21. Gomez-Raposo C, Zambrana Tevar F, Sereno Moyano M, Lopez Gomez M, Casado E (2010) Male breast cancer. Cancer Treat Rev 36:451–457. doi:10.1016/j.ctrv.2010.02.002

    Article  PubMed  Google Scholar 

  22. Evans DG, Susnerwala I, Dawson J, Woodward E, Maher ER, Lalloo F (2010) Risk of breast cancer in male BRCA2 carriers. J Med Genet 47:710–711. doi:10.1136/jmg.2009.075176

    Article  PubMed  CAS  Google Scholar 

  23. Brinton LA (2011) Breast cancer risk among patients with Klinefelter syndrome. Acta Paediatr. doi:10.1111/j.1651-2227.2010.02131.x

  24. Onami S, Ozaki M, Mortimer JE, Pal SK (2010) Male breast cancer: an update in diagnosis, treatment and molecular profiling. Maturitas 65:308–314. doi:10.1016/j.maturitas.2010.01.012

    Article  PubMed  CAS  Google Scholar 

  25. Ferro P, Catalano MG, Dell’Eva R, Fortunati N, Pfeffer U (2002) The androgen receptor CAG repeat: a modifier of carcinogenesis? Mol Cell Endocrinol 193:109–120. doi:10.1016/S0303-7207(02)00104-1

    Article  PubMed  CAS  Google Scholar 

  26. Lindstrom S, Ma J, Altshuler D, Giovannucci E, Riboli E, Albanes D, Allen NE, Berndt SI, Boeing H, Bueno-de-Mesquita HB, Chanock SJ, Dunning AM, Feigelson HS, Gaziano JM, Haiman CA, Hayes RB, Henderson BE, Hunter DJ, Kaaks R, Kolonel LN, Le Marchand L, Martinez C, Overvad K, Siddiq A, Stampfer M, Stattin P, Stram DO, Thun MJ, Trichopoulos D, Tumino R, Virtamo J, Weinstein SJ, Yeager M, Kraft P, Freedman ML (2010) A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk results from the national cancer institute breast and prostate cancer cohort consortium. J Clin Endocrinol Metab 95:E121–E127. doi:10.1210/jc.2009-1911

    Article  PubMed  Google Scholar 

  27. Chamberlain NL, Driver ED, Miesfeld RL (1994) The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 22:3181–3186. doi:10.1093/nar/22.15.3181

    Article  PubMed  CAS  Google Scholar 

  28. Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, Moore NL, Raynor M, Neufing PJ, Coetzee GA, Tilley WD (2004) Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet 13:1677–1692. doi:10.1093/hmg/ddh181

    Article  PubMed  CAS  Google Scholar 

  29. Esteban E, Rodon N, Via M, Gonzalez-Perez E, Santamaria J, Dugoujon JM, Chennawi FE, Melhaoui M, Cherkaoui M, Vona G, Harich N, Moral P (2006) Androgen receptor CAG and GGC polymorphisms in Mediterraneans: repeat dynamics and population relationships. J Hum Genet 51:129–136. doi:10.1007/s10038-005-0336-7

    Article  PubMed  CAS  Google Scholar 

  30. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN (2004) Breast carcinoma in men: a population-based study. Cancer 101:51–57. doi:10.1002/cncr.20312

    Article  PubMed  Google Scholar 

  31. Dey S, Soliman AS, Hablas A, Seifeldin I, Ismail K, Ramadan M, El-Hamzawy H, Wilson ML, Banerjee M, Boffetta P, Harford J, Merajver SD (2010) Urban rural differences in breast cancer incidence by hormone receptor status across 6 years in Egypt. Breast Cancer Res Treat 120:149–160. doi:10.1007/s10549-009-0427-9

    Article  PubMed  CAS  Google Scholar 

  32. Felix AS, Soliman AS, Khaled H, Zaghloul MS, Banerjee M, El-Baradie M, El-Kalawy M, Abd-Elsayed AA, Ismail K, Hablas A, Seifeldin IA, Ramadan M, Wilson ML (2008) The changing patterns of bladder cancer in Egypt over the past 26 years. Cancer Causes Control 19:421–429. doi:10.1007/s10552-007-9104-7

    Article  PubMed  Google Scholar 

  33. Blanco S, Suarez A, Gandia-Pla S, Gomez-Llorente C, Antunez A, Gomez-Capilla JA, Farez-Vidal ME (2008) Use of capillary electrophoresis for accurate determination of CAG repeats causing Huntington disease. An oligonucleotide design avoiding shadow bands. Scand J Clin Lab Invest 9:1–8. doi:10.1080/00365510801915171

    Google Scholar 

  34. Young IE, Kurian KM, Mackenzie MA, Kunkler IH, Cohen BB, Hooper ML, Wyllie AH, Steel CM (2000) The CAG repeat within the androgen receptor gene in male breast cancer patients. J Med Genet 37:139–140. doi:10.1136/jmg.37.2.139

    Article  PubMed  CAS  Google Scholar 

  35. MacLean HE, Brown RW, Beilin J, Warne GL, Zajac JD (2004) Increased frequency of long androgen receptor CAG repeats in male breast cancers. Breast Cancer Res Treat 88:239–246. doi:10.1007/s10549-004-0781-6

    Article  PubMed  CAS  Google Scholar 

  36. Syrjakoski K, Hyytinen ER, Kuukasjarvi T, Auvinen A, Kallioniemi OP, Kainu T, Koivisto PA (2003) Androgen receptor gene alterations in Finnish male breast cancer. Breast Cancer Res Treat 77:167–170. doi:10.1023/A:1021369508561

    Article  PubMed  Google Scholar 

  37. Badran WA, Fahmy I, Abdel-Megid WM, Elder K, Mansour R, Kent-First M (2009) Length of androgen receptor-CAG repeats in fertile and infertile Egyptian men. J Androl 30:416–425. doi:10.2164/jandrol.108.005843

    Article  PubMed  CAS  Google Scholar 

  38. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, Statistics Subcommittee G of NCI-EORTC Working group on Cancer Diagnostics (2006) Reporting recommendations for tumor marker prognostic studies (REMARK). Breast Cancer Res Treat 100:229–235. doi:10.1007/s10549-006-9242-8

    Article  PubMed  Google Scholar 

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Acknowledgments

This research, Samuel Gilbert, and Ashley Strahley, were supported by the Cancer Epidemiology Education in Special Populations Program of the University of Michigan, an R25 Cancer Education Grant from the National Cancer Institute (R25 CA112383). The work was also supported by the Breast Cancer Research Foundation, the Avon Foundation, the Debbie Strange-Brown Inflammatory Breast Cancer Foundation, and the Tempting Tables Organization. The authors of this study would like to thank Dr. Khaled Daboos of the Tanta Cancer Center for his generous assistance in collecting blood samples to use as controls and Dr. Leon Raskin at the University of Michigan for his valuable guidance in interpreting the allele fragment analyses.

Conflict of interest

The authors do not have any to declare. This study was reported taking into consideration the REMARK guidelines.

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Correspondence to Amr S. Soliman.

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Gilbert, S.F., Soliman, A.S., Iniesta, M. et al. Androgen receptor polyglutamine tract length in Egyptian male breast cancer patients. Breast Cancer Res Treat 129, 575–581 (2011). https://doi.org/10.1007/s10549-011-1510-6

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