Group-specific component and 25-hydroxylase gene polymorphisms in nasopharyngeal carcinoma: Associations with susceptibility and radiotherapy response

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC), exhibiting high incidence in southern China, is linked to genetic and environmental factors. Vitamin D metabolism, involving transport [group-specific component (GC) protein] and activation [25-hydroxylase (CYP2R1) enzyme], may influence NPC susceptibility and radiotherapy response. Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D [25(OH)D] levels, and are implicated in other cancers. However, their role in NPC – particularly in high-risk Han Chinese populations – and interaction with vitamin D status remains unclear. This case control study (360 NPC patients, 550 controls) investigates these relationships to inform prevention and personalized therapy.

AIM

To investigate the association between vitamin D binding protein (GC) and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.

METHODS

A case control study design was adopted, and 360 patients with NPC and 550 healthy controls were included. TaqMan method was used to perform genotyping on GC gene loci rs4588, rs7041, and CYP2R1 gene loci rs10741657, rs12794714. Serum 25(OH)D levels were detected, and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.

RESULTS

The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model [odds ratio (OR) = 1.68, 95%CI: 1.15-2.45, P = 0.007] and the recessive model (OR = 1.56, 95%CI: 1.02-2.38, P = 0.039). The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup (OR = 1.87, 95%CI: 1.11-3.15, P = 0.019) and the squamous cell carcinoma subgroup (OR = 1.89, 95%CI: 1.19-3.00, P = 0.007). The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype (P < 0.001). The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels (P = 0.003). The rs12794714 AA genotype was associated with radiotherapy resistance (OR = 1.76, 95%CI: 1.18-2.63, P = 0.005). Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.

CONCLUSION

GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response, and this association may be affected by serum 25(OH)D levels. This study provides a new idea for the prevention and individualized treatment in NPC.

Keywords: Group-specific component protein; 25-hydroxylase; Single nucleotide polymorphism; Nasopharyngeal carcinoma; Susceptibility; Radiotherapy response

Core Tip: This study reveals that polymorphisms in the vitamin D-binding protein gene [group-specific component (GC), rs4588] and 25-hydroxylase gene (CYP2R1) (rs12794714) are associated with nasopharyngeal carcinoma (NPC) susceptibility and radiotherapy response, particularly in individuals with sufficient serum 25-hydroxyvitamin D levels. The GC rs4588 TT genotype increases NPC risk, while the CYP2R1 rs12794714 AA genotype predicts radiotherapy resistance. These findings highlight the interplay between genetic predisposition and vitamin D status, offering new strategies for precision prevention and personalized treatment in NPC.