Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Lack of Association of the NPAS2 Gene Ala394Thr Polymorphism (rs2305160:G>A) with Risk of Chronic Lymphocytic Leukemia

  • Rana, Sobia (Department of Physiology and Cell Biology, University of Health Sciences) ;
  • Shahid, Adeela (Department of Physiology and Cell Biology, University of Health Sciences) ;
  • Ullah, Hafeez (Department of Allied Health Sciences, University of Health Sciences) ;
  • Mahmood, Saqib (Department of Human Genetics & Molecular Biology, University of Health Sciences)
  • Published : 2014.09.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

Keywords

References

  1. Asher G, Schibler U (2006). A CLOCK-less clock. Trends Cell Biol, 16, 547-49. https://doi.org/10.1016/j.tcb.2006.09.005
  2. Bartsch C, Bartsch H, Schmidt A, et al (1992). Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: evidence for reduced pineal activity and relevance of urinary determinations. Clin Chim Acta, 209, 153-67. https://doi.org/10.1016/0009-8981(92)90164-L
  3. Bertolucci C, Cavallari N, Colognesi I, et al (2008). Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators. Mol Cell Biol, 28, 3070-75. https://doi.org/10.1128/MCB.01931-07
  4. Chen-Goodspeed M, Lee CC (2007). Tumor suppression and circadian function. J Biol Rhythms, 22, 291-98. https://doi.org/10.1177/0748730407303387
  5. Chu LW, Zhu Y, Yu K, et al (2008). Variants in circadian genes and prostate cancer risk: a population-based study in China. Prostate Cancer Prostatic Dis, 11, 342-48. https://doi.org/10.1038/sj.pcan.4501024
  6. Costa G, Haus E, Stevens R (2010). Shift work and cancer - considerations on rationale, mechanisms, and epidemiology. Scand J Work Environ Health, 36, 163-79. https://doi.org/10.5271/sjweh.2899
  7. DeBruyne JP, Weaver DR, Reppert SM (2007). CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci, 10, 543-45. https://doi.org/10.1038/nn1884
  8. Dohner H, Stilgenbauer K, Dohner M (1999). Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis. J Mol Med, 77, 266-81. https://doi.org/10.1007/s001090050350
  9. Fujino Y (2007). Occupational factors and mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC). Asian Pac J Cancer Prev, 8, 97-104.
  10. Fu L, Lee CC (2003). The circadian clock: pacemaker and tumour suppressor. Nat Rev Cancer, 3, 350-61. https://doi.org/10.1038/nrc1072
  11. Fu L, Pelicano H, Liu J, Huang P, Lee C (2002). The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell, 111, 41-50. https://doi.org/10.1016/S0092-8674(02)00961-3
  12. Hoffman AE, Zheng T, Ba Y, Zhu Y (2008). The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. Mol Cancer Res, 6, 1461-68. https://doi.org/10.1158/1541-7786.MCR-07-2094
  13. Howlader N, Noone AM, Krapcho M, et al (2012). SEER Cancer Statistics Review 1975-2009 (Vintage 2009 Populations). National Cancer Institute, Bethesda, MD. http:// seer.cancer.gov.
  14. Kermani IA, Dehdilani M, Dolatkhah R (2007). Chronic lymphocytic leukemia in the recent 10 years and treatment effects of Fludarabin. Asian Pac J Cancer Prev, 8, 367-71.
  15. Kucuktulu E (2012). Protective effect of melatonin against radiation induced nephrotoxicity in rats. Asian Pac J Cancer Prev, 13, 4101-05. https://doi.org/10.7314/APJCP.2012.13.8.4101
  16. Luo Y, Wang F, Chen LA, et al (2012). Deregulated expression of cry1 and cry2 in human gliomas. Asian Pac J Cancer Prev, 13, 5725-28. https://doi.org/10.7314/APJCP.2012.13.11.5725
  17. Mirick DK, Davis S (2008). Melatonin as a biomarker of circadian dysregulation. Cancer Epidemiol Biomarkers Prev, 17, 3306-13. https://doi.org/10.1158/1055-9965.EPI-08-0605
  18. Mozaheb Z, Hasanzadeh NazarAbadi MH, Aghaee MA (2012). Chronic lymphocytic leukemia and prognostic factors. Asian Pac J Cancer Prev, 13, 3009-13. https://doi.org/10.7314/APJCP.2012.13.7.3009
  19. Oscier D, Fegan C, Hillmen P, et al (2004). British Committee for Standards in Haematology. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br J Haematol, 125, 294-317. https://doi.org/10.1111/j.1365-2141.2004.04898.x
  20. Schernhammer ES, Hankinson SE (2009). Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses' Health Study cohort. Cancer Epidemiol Biomarkers Prev, 18, 74-9. https://doi.org/10.1158/1055-9965.EPI-08-0637
  21. Sgambati MT, Linet MS, Devesa SS (2001). Chronic Lymphocytic Leukemia: Epidemiological, Familial, and Genetic Aspests. In 'Chronic Lymphoid Leukemias', Eds Cheson BD, Marcel Dekker, New York pp 33-62.
  22. Straif K, Baan R, Grosse Y (2007). Carcinogenicity of shiftwork, painting, and fire-fighting. Lancet Oncol, 8, 1065-66. https://doi.org/10.1016/S1470-2045(07)70373-X
  23. Wang F, Hu Z, Yang R, et al (2011). A variant affecting miRNAs binding in the circadian gene neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk. Breast Cancer Res Treat, 127, 769-75. https://doi.org/10.1007/s10549-010-1157-8
  24. Yi CH, Zheng T, Leaderer D, Hoffman A, Zhu Y (2009). Cancerrelated transcriptional targets of the circadian gene NPAS2 identified by genome-wide ChIP-on-chip analysis. Cancer Lett, 284, 149-56. https://doi.org/10.1016/j.canlet.2009.04.017
  25. Yi C, Mu L, de la Longrais IA, et al (2010). The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer. Breast Cancer Res Treat, 120, 663-69. https://doi.org/10.1007/s10549-009-0484-0
  26. Yuan P, Wang S, Zhou F, et al (2014). Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization- treated hepatocellular carcinoma patients. Cancer Sci, 105, 825-32. https://doi.org/10.1111/cas.12428
  27. Zhou YD, Barnard M, Tian H, et al (1997). Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. Proc Natl Acad Sci USA, 94,713-18. https://doi.org/10.1073/pnas.94.2.713
  28. Zhu Y, Leaderer D, Guss C, et al (2007). Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma. Int J Cancer, 120, 432-35. https://doi.org/10.1002/ijc.22321
  29. Zhu Y, Stevens RG, Leaderer D, et al (2008). Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk. Breast Cancer Res Treat, 107, 421-5. https://doi.org/10.1007/s10549-007-9565-0

Cited by

  1. NPAS2 promotes cell survival of hepatocellular carcinoma by transactivating CDC25A vol.8, pp.3, 2017, https://doi.org/10.1038/cddis.2017.131
  2. Melatonin: does it have utility in the treatment of haematological neoplasms? pp.00071188, 2017, https://doi.org/10.1111/bph.13966