C2CD4A/B variants in the predisposition of lung cancer in the Chinese Han population

Funct Integr Genomics. 2022 Jun;22(3):331-340. doi: 10.1007/s10142-022-00827-x. Epub 2022 Feb 25.

Abstract

Background: The mRNA levels of C2CD4A and C2CD4B were dysregulation in lung cancer (LC). We aimed to evaluate the role of C2CD4A/B variants in LC susceptibility.

Methods: There were 710 cases with LC and 710 healthy controls enrolled in the study. The genotyping of twelve variants in C2CD4A/B was carried out by Agena MassARRAY system. Odds ratios (ORs) were calculated by logistic regression analysis to assess the relationship between these variants and LC predisposition.

Results: Rs8037894 (OR = 0.81, p = 0.005), rs7172432 (OR = 0.83, p = 0.013), rs11856307 (OR = 0.86, p = 0.043), and rs1436953 (OR = 0.79, p = 0.002) were related to the reduced risk of LC. Besides, the relation of rs7172432 with LC risk in subjects aged > 60 years was observed. Rs4502156 conferred to the increased LC risk, while rs1436953 was associated with the lower susceptibility to LC among males. Rs731820, rs4502156, rs11071657, rs7172432, and rs11856307 contributed to the predisposition of LC among subjects with BMI > 24 kg/m2, while rs7495253 was associated with an increased risk of LC in subjects with BMI ≤ 24 kg/m2. The increased LC risk was found in rs4502156, while the protective risk effect of rs8037894, rs7172432, rs11856307, and rs1436953 on the occurrence of LC was observed in smokers and non-drinkers. Moreover, rs7495253 and rs7495931 had a higher risk of lymphatic metastasis. Rs1436953 was related to the reduced risk of lung adenocarcinoma, while rs4502156, rs8037894, rs7172432, rs11856307, and rs1436953 were related to the risk of small cell carcinoma.

Conclusions: Our results first display that C2CD4A/B polymorphisms served as protective factors for LC predisposition in a Chinese Han population. These findings could provide new biological insight into the understanding of C2CD4A/B genes on LC pathogenesis.

Keywords: C2CD4A/B polymorphisms; Lung cancer; SNP-SNP interaction; Stratification analysis.

MeSH terms

  • Case-Control Studies
  • China
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lung Neoplasms* / genetics
  • Male
  • Middle Aged
  • Nuclear Proteins* / genetics
  • Polymorphism, Single Nucleotide
  • Transcription Factors* / genetics

Substances

  • C2CD4A protein, human
  • C2CD4B protein, human
  • Nuclear Proteins
  • Transcription Factors