Genetic polymorphisms and plasma levels of BCL11A contribute to the development of laryngeal squamous cell carcinoma

PLoS One. 2017 Feb 22;12(2):e0171116. doi: 10.1371/journal.pone.0171116. eCollection 2017.

Abstract

Objective: We investigated the association between B-cell lymphoma/leukaemia 11A (BCL11A) rs11886868 and rs4671393 polymorphism, plasma BCL11A concentration, and the hazard of developing laryngeal squamous cell carcinoma (LSCC).

Participants and method: In this research, 330 LSCC patients, 310 healthy controls, and 155 vocal leukoplakia patients were genotyped for the BCL11A (rs11886868 C/T and rs4671393 A/G) genotypes by pyrosequencing; the BCL11A concentration was measured using ELISA.

Results: LSCC Patients had a notably higher occurrence of CT at rs11886868 (OR = 2.64, P = 0.025) than the control group; they also had higher GG at rs4671393 (OR = 2.53, P = 0.018). Advanced (III and IV) stage LSCC patients had a notably greater frequency of CT at rs11886868 than those with initial (I and II) stage LSCC (OR = 2.71, P = 0.044 vs. OR = 2.58, P = 0.051). Additionally, there was a 1.59 fold increase in susceptibility for initial stage LSCC related to the G allele (AG/GG) at rs4671393 (P = 0.005); while for patients of advanced stage LSCC the OR was 1.73 (P = 0.002). Moreover, the OR of lymph node metastasis patients at rs4671393 G alleles was 2.41 (P < 0.01); it was 1.38 (P = 0.035) in patients without lymph metastasis. Patients with high incidences of the rs4671393 variation genotype had high plasma BCL11A levels.

Conclusions: BCL11A rs11886868 and rs4671393 genotype variations and correspondingly high BCL11A plasma levels are related to LSCC, besides, differences in plasma levels and genotype distribution may be related to lymph node metastasis status and the stage of LSCC.

MeSH terms

  • Aged
  • Alleles
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carrier Proteins / blood*
  • Carrier Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Laryngeal Neoplasms / blood
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • Middle Aged
  • Nuclear Proteins / blood*
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Repressor Proteins

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • Nuclear Proteins
  • Repressor Proteins

Grants and funding

Funded by Shanghai Science and Technology Development Funds 09QA1401000, 10QA1405900 Training Program of the Excellent Young Talents of the Shanghai Municipal Health System XYQ2011055, XYQ2011015, Shanghai Municipal Science and Technology Foundation 11JC1410802, 14411961900, National Natural Science Foundation of China 81671579, 31370904, 30972691, Shanghai Pujiang Program 15PJD021 Program for scientific and technological innovation from the Science and Technology Commission of Shanghai Municipality 15401900500, and Shuguang Planning of Shanghai Municipal Education Commission 16SG14.