Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer

Surg Oncol. 2017 Sep;26(3):278-285. doi: 10.1016/j.suronc.2017.05.004. Epub 2017 May 22.

Abstract

Background: Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients.

Methods: A prospective cohorts study was performed, including 170 NSCLC patients (114 Stage IIIB-IV, 56 Stage I-IIIA). IL1B (C > T; rs1143634), IL1B (C > T; rs12621220), IL1B (C > G; rs1143623), IL1B (A > G; rs16944), IL1B (C > T; rs1143627), IL6 (C > G; rs1800795), IL12A (C > T; rs662959), IL13 (A > C; rs1881457) and IL16 (G > T; rs7170924) gene polymorphisms were analyzed by PCR Real-Time.

Results: Patients with IL16 rs7170924-GG genotype were in higher risk of death (p = 0.0139; HR = 1.82; CI95% = 1.13-2.94) Furthermore, carriers of the TT genotype for IL12A rs662959 presented higher risk of progression in the non-resected NSCLC patient subgroup (p = 0.0412; HR = 4.49; CI95% = 1.06-18.99). The rest of polymorphisms showed no effect of on outcomes.

Conclusions: Our results suggest that IL16 rs7170924-GG and IL12A rs662959-TT genotypes predict higher risk of death and progression, respectively, in NSCLC patients. No influence of IL1B rs12621220, IL1B rs1143623, IL1B rs16944, IL1B rs1143627, IL6 rs1800795, IL13 rs1881457 on NSCLC clinical outcomes was found in our patients.

Keywords: Interleukins; Non-small cell lung cancer; Platinum based chemotherapy; Polymorphisms; Survival.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Disease Progression
  • Early Detection of Cancer
  • Female
  • Genetic Markers / physiology
  • Genotype
  • Humans
  • Interleukin-12 Subunit p35 / genetics*
  • Interleukin-12 Subunit p35 / metabolism
  • Interleukin-16
  • Interleukins / genetics
  • Interleukins / metabolism
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • Genetic Markers
  • IL12A protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-16
  • Interleukins