Advertisement

Molecular Biology Reports

, Volume 41, Issue 9, pp 6111–6115 | Cite as

PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors

  • Gisele M. Vasconcelos
  • Bruno Aguiar Alves Gonçalves
  • Rafaela Montalvão-de-Azevedo
  • Luiz Claúdio Santos Thuler
  • Flavio Henrique Paraguassu Braga
  • Maria S. Pombo-de-OliveiraEmail author
  • Beatriz de CamargoEmail author
  • Brazilian Embryonal Tumor Group
Article

Abstract

Genetic susceptibility and environment exposures are associated risk factors in carcinogenesis. Gene polymorphisms that decrease the activity of detoxifying carcinogen substances may modify the effect of exposures. We investigated whether the polymorphisms PON1 rs662 (Q192R), and PON1 rs854560 (L55M) would be associated with embryonal tumors in Brazilian children. Blood samples from 163 children with embryonal tumors and 342 as control group were genotyped by TaqMAN real-time PCR assays. Logistic regression was used to evaluate the association between the polymorphisms of cases and controls groups, adjusted by skin color and age strata. When all tumors were taken together, the presence of the PON1 rs662 (Q192R) variant genotype (RR) was associated with an increased risk of developing embryonal tumors (OR = 2.80, 95 % CI 1.12–7.02). The presence of at least one variant PON1 rs662 R allele increased the risk of developing Wilms´ Tumor although without statistical power. However, it was observed a significant association of PON1 rs662 (Q192R) variant genotype (RR) with retinoblastoma (OR = 4.08, 95 % CI 1.13–14.97), whereas the PON1 rs854560 (L55M) polymorphism was not associated with any tumor. These results indicate that PON1 polymorphisms may have an influence on the risk of developing embryonal tumors.

Keywords

Embryonal tumors Genetic susceptibility PON1 polymorphisms Wilms tumor Neuroblastoma Retinoblastoma 

Notes

Conflict of interest

All authors disclose that no financial or personal relationships with other individuals or organizations have inappropriately influenced this study.

Authors’ contributions

GMV, BAAG, BDC contributed to study design, data collection, interpretation, and manuscript writing. MSPO has supported the study, discussed data interpretation, and reviewed the manuscript. RMV and BAAG contributed equally to all laboratory work. LCST performed statistical analysis. The Brazilian Embryonal Study group members provided clinical and biological data collection. All authors read and approved the manuscript. BDC and MSPO have scholarships grants from CNPq # 311511/2009-0 and # 309091/2007-1, respectively.

References

  1. 1.
    Cole TB, Jampsa RL, Walter BJ et al (2003) Expression of human paraoxonase (PON1) during development. Pharmacogenetics 13:357–364CrossRefPubMedGoogle Scholar
  2. 2.
    Huen K, Harley K, Brooks J et al (2009) Developmental changes in PON1 enzyme activity in young children and effects of PON1 polymorphisms. Environ Health Perspect 117:1632–1638PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Ferreira JD, Couto AC, Pombo-de-Oliveira MS, Koifman S, Brazilian Collaborative Study Group of Infant Acute Leukemia (2013) In utero pesticide exposure and leukemia in Brazilian children < 2 years of age. Environ Health Perspect 121:269–275PubMedCentralPubMedGoogle Scholar
  4. 4.
    Delgado IF, Paumgartten FJ (2004) Pesticide use and poisoning among farmers from the county of Paty do Alferes, Rio de Janeiro, Brazil. Cad Saúde Pública 20:180–186CrossRefPubMedGoogle Scholar
  5. 5.
    Searles Nielsen S, Mueller BA, De Roos AJ, Viernes HM, Farin FM, Checkoway H (2005) Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1). Environ Health Perspect 113:909–913CrossRefPubMedGoogle Scholar
  6. 6.
    de Aguiar Gonçalves BA, Vasconcelos GM, Thuler LC, Andrade C, Faro A, Pombo-de-Oliveira MS, Brazilian Collaborative Study Group of Infant Acute Leukemia (2012) NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemia according to age range distribution. Cancer Causes Control 23:1811–1819CrossRefPubMedGoogle Scholar
  7. 7.
    de Camargo B, de Oliveira Santos M, Rebelo MS et al (2010) Cancer incidence among children and adolescents in Brazil: first report of 14 population-based cancer registries. Int J Cancer 126:715–720CrossRefPubMedGoogle Scholar
  8. 8.
    Searles Nielsen S, McKean-Cowdin R, Farin FM, Holly EA, Preston-Martin S, Mueller BA (2010) Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes. Environ Health Perspect 118(1):144–149PubMedGoogle Scholar
  9. 9.
    Jurewicz J, Hanke W (2006) Exposure to pesticides and childhood cancer risk: has there been any progress in epidemiological studies? Int J Occup Med Environ Health 19:152–169CrossRefPubMedGoogle Scholar
  10. 10.
    Vinson F, Merhi M, Baldi I, Raynal H, Gamet-Payrastre L (2011) Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies. Occup Environ Med 68:694–702CrossRefPubMedGoogle Scholar
  11. 11.
    Perera FP (1997) Environment and cancer: who are susceptible? Science 278(5340):1068–1073CrossRefPubMedGoogle Scholar
  12. 12.
    Alexander FE, Patheal SL, Biondi A et al (2001) Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res 61:2542–2546PubMedGoogle Scholar
  13. 13.
    Pombo-de-Oliveira MS, Koifman S, Brazilian Collaborative Study Group of Infant Acute Leukemia (2006) Infant acute leukemia and maternal exposures during pregnancy. Cancer Epidemiol Biomark Prev 15:2336–2341CrossRefGoogle Scholar
  14. 14.
    Zanrosso CW, Emerenciano M, Goncalves BA, Faro A, Koifman S, Pombo-de-Oliveira MS (2010) N-acetyltransferase 2 polymorphisms and susceptibility to infant leukemia with maternal exposure to dipyrone during pregnancy. Cancer Epidemiol Biomark Prev 19:3037–3043CrossRefGoogle Scholar
  15. 15.
    Cooney MA, Daniels JL, Ross JA, Breslow NE, Pollock BH, Olshan AF (2007) Household pesticides and the risk of Wilms tumor. Environ Health Perspect 115:134–137PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Sharpe CR, Franco EL, de Camargo B et al (1995) Parental exposures to pesticides and risk of Wilms’ tumor in Brazil. Am J Epidemiol 141:210–217PubMedGoogle Scholar
  17. 17.
    Heck JE, Ritz B, Hung RJ, Hashibe M, Boffetta P (2009) The epidemiology of neuroblastoma: a review. Paediatr Perinat Epidemiol 23:125–143CrossRefPubMedGoogle Scholar
  18. 18.
    Abdolahi A, van Wijngaarden E, McClean MD et al (2013) A case-control study of paternal ccupational exposures and the risk of childhood sporadic bilateral retinoblastoma. Occup Environ Med 70:372–379PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Pakakasama S, Tomlinson GE (2002) Genetic predisposition and screening in pediatric cancer. Pediatr Clin North Am 49:1393–1413CrossRefPubMedGoogle Scholar
  20. 20.
    Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 69:541–550CrossRefPubMedGoogle Scholar
  21. 21.
    Costa LG, Giordano G, Cole TB, Marsillach J, Furlong CE (2013) Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity. Toxicology 307:115–122PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Gisele M. Vasconcelos
    • 1
  • Bruno Aguiar Alves Gonçalves
    • 1
  • Rafaela Montalvão-de-Azevedo
    • 1
  • Luiz Claúdio Santos Thuler
    • 2
  • Flavio Henrique Paraguassu Braga
    • 3
  • Maria S. Pombo-de-Oliveira
    • 1
    Email author
  • Beatriz de Camargo
    • 1
    Email author
  • Brazilian Embryonal Tumor Group
  1. 1.Pediatric Hematology-Oncology Program, Research CenterInstituto Nacional de CâncerRio de JaneiroBrazil
  2. 2.Clinical Research, Research CenterInstituto Nacional de CâncerRio de JaneiroBrazil
  3. 3.National Cord Blood BankInstituto Nacional de CâncerRio de JaneiroBrazil

Personalised recommendations