Abstract
A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats—(CAG)n—in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (<7), as well as early onset (<60 years) or late onset PC (⩾60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14–4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.
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References
Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 Internet. Lyon, France (2013): International Agency for Research on Cancer. http://globocan.iarc.fr. Accessed 13 March 2016.
Gomez-Guerra, L. S., Martinez-Fierro, M. L., Alcantara-Aragon, V., Ortiz-Lopez, R., Martinez-Villarreal, R. T., Morales-Rodriguez, I. B. et al. Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases. BMC Cancer 9, 91–96 (2009).
Grönberg, H. Prostate cancer epidemiology. Lancet 361, 859–864 (2003).
Lichtenstein, P., Holm, N. V., Verkasalo, P. K., Iliadou, A., Kaprio, J., Koskenvuo, M. et al. Environmental and heritable factors in the causation of cancer- analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).
Bosland, M. C. & Mahmoud, A. M. Hormones and prostate carcinogenesis: androgens and estrogens. J. Carcinog. 10, 33 (2011).
Koochekpour, S. Androgen receptor signaling and mutations in prostate cancer. Asian J. Androl. 12, 639–657 (2010).
Buchanan, G., Yang, M., Cheong, A., Harris, J. M., Irvine, R. A., Lambert, P. F. et al. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum. Mol. Genet 13, 1677–1692 (2004).
Beilin, J., Ball, E. M., Favaloro, J. M. & Zajac, J. D. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J. Mol. Endocrinol. 25, 85–96 (2000).
Gu, M., Dong, X., Zhang, X. & Niu, W. The CAG repeat polymorphism of androgen receptor gene and prostate cancer: a meta-analysis. Mol. Biol. Rep. 39, 2615–2624 (2012).
Sun, J. H. & Lee, S. A. Association between CAG repeat polymorphisms and the risk of prostate cancer: a meta-analysis by race, study design and the number of (CAG)n repeat polymorphisms. Int. J. Mol. Med. 32, 1195–1203 (2013).
Williams, H. & Powell, I. J. Epidemiology, pathology, and genetics of prostate cancer among African Americans compared with other ethnicities. Methods Mol. Biol. 472, 439–453 (2009).
Ackerman, C. M., Lowe, L. P., Lee, H., Hayes, M. G., Dyer, A. R., Metzger, B. E. et al. Ethnic variation in allele distribution of the androgen receptor (AR) (CAG)n repeat. J. Androl. 33, 210–215 (2012).
Balic, I., Graham, S. T., Troyer, D. A., Higgins, B. A., Pollock, B. H., Johnson-Pais, T. L. et al. Androgen receptor length polymorphism associated with prostate cancer risk in Hispanic men. J. Urol. 168, 2245–2248 (2002).
Freedman, M. L., Pearce, C. L., Penney, K. L., Hirschhorn, J. N., Kolonel, L. N., Henderson, B. E. et al. Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study. Am. J. Hum. Genet. 76, 82–90 (2005).
Vázquez-Salas, R. A., Torres-Sánchez, L., López-Carrillo, L., Romero-Martínez, M., Manzanilla-García, H. A., Cruz-Ortíz, C. H. et al. History of gonorrhea and prostate cancer in a population-based case-control study in Mexico. Cancer Epidemiol. 40, 95–101 (2016).
Silviu-Alin, B., Devlin, B. & Roeder, K. The power of genomic control. Am. J. Hum. Genet. 66, 1933–1944 (2000).
Noris, G., Santana, C., Meraz-Ríos, M. A., de Lourdes Muñoz, M., Majluf-Cruz, A., Magaña, J. J. et al. Mexican mestizo population sub-structure: effects on genetic and forensic statistical parameters. Mol. Biol. Rep. 39, 10139–10156 (2012).
Westberg, L., Henningsson, S., Landén, M., Annerbrink, K., Melke, J., Nilsson, S. et al. Influence of androgen receptor repeat polymorphisms on personality traits in men. J. Psychiatry Neurosci. 34, 205–213 (2009).
Humphrey, P. A. Gleason grading and prognostic factors in carcinoma of the prostate. Mod. Pathol. 17, 292–306 (2004).
Excoffier, L., Laval, G. & Schneider, S. Arlequin ver. 3.1: An integrated software package for population genetics data analysis. Evol. Bioinform. Online 1, 47–50 (2005).
Belkhir, L. C., Raufaste, N. & Bonhomme, F. in GENETIX 4.05 Logiciel Sous Windows TM Pour la Génétique des Populations. (eds Laboratoire Génome P) Interactions, CNRS UMR 5171 (Université de Montpellier II, Montpellier, 1996–2004).
Meneses-García, A., Ruiz-Godoy, L. M., Beltrán-Ortega, A., Sánchez-Cervantes, F., Tapia-Conyer, R. & Mohar, A. Principales neoplasias malignas en México y su distribución geográfica (1993-2002). Rev. Inv. Clin. 64, 322–329 (2012).
Bratt, O., Borg, A., Kristoffersson, U., Lundgren, R., Zhang, Q. X. & Olsson, H. CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk. Br. J. Cancer 81, 672–676 (1999).
Mao, X., Li., J., Xu, X., Boyd, L. K., He, W., Stankiewicz, E. et al. Involvement of different mechanisms for the association of CAG repeat length polymorphism in androgen receptor gene with prostate cancer. Am. J. Cancer Res 4, 886–896 (2014).
Yoshimoto, M., Joshua, A. M., Cunha, I. W., Coudry, R. A., Fonseca, F. P., Ludkovski, O. et al. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod. Pathol. 21, 1451–1460 (2008).
Patiño-García, B., Arroyo, C., Rangel-Villalobos, H., Soto-Vega, E., Velarde-Félix, J. S., Gabilondo, F. et al. Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population. Rev. Invest. Clin. 59, 25–31 (2007).
Acknowledgements
This study was supported by CONACyT grant number 140482 (to LT-S). We are grateful for the contribution of Arianna Ventura-Bahena, and of Ms Nicol Ventura-Bahena, who participated in the conformation of the samples bank and the coding and entering of the information, respectively. Likewise, we are grateful to each of the participating hospitals: General Hospital of Mexico (SSA), National Cancer Institute (SSA), Salvador Zubirán National Institute of Medical and Nutrition Sciences (SSA), and the Centro Médico Nacional Siglo XXI Oncology Hospital (IMSS), the Dr Carlos McGregor Sánchez Navarro Regional General Hospital No.1 (IMSS) and the Adolfo López Mateos Regional Hospital (ISSSTE). We also thank Laboratorio de Genómica, Proteómica y Metabolómica from LaNSE-Cinvestav for helping with the genotyping processes.
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Gómez, R., Torres-Sánchez, L., Camacho-Mejorado, R. et al. Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men. J Hum Genet 61, 781–786 (2016). https://doi.org/10.1038/jhg.2016.49
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DOI: https://doi.org/10.1038/jhg.2016.49
