HLA class II polymorphisms as prognostic biomarkers for right and left-sided colon cancer

Int J Biol Markers. 2024 Mar;39(1):40-51. doi: 10.1177/03936155231224469. Epub 2024 Jan 5.

Abstract

Background: Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested.

Aim of the study: We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC.

Patients and methods: Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP).

Results: DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC.

Conclusion: DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC.

Keywords: HLA-DQB1; HLA-DRB1; PCR-SSP; left-sided colon cancer; right-sided colon cancer.

MeSH terms

  • Alleles
  • Carcinoma, Renal Cell*
  • Colonic Neoplasms* / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-DQ beta-Chains / genetics
  • Haplotypes
  • Humans
  • Kidney Neoplasms*
  • Prognosis

Substances

  • HLA-DQ beta-Chains