Association analysis of interleukin-18 gene promoter region polymorphisms and susceptibility to sporadic breast cancer in Chinese Han women

J Clin Lab Anal. 2018 Nov;32(9):e22591. doi: 10.1002/jcla.22591. Epub 2018 Jun 21.

Abstract

Background: Interleukin-18-137G/C, -607G/T polymorphisms play multiple roles in various cancers. However, studies focused on its involvement in breast cancer remain controversial, and no study has taken the interaction between interleukin-18 (IL-18) gene polymorphism and body mass index (BMI), menopause into consideration. The study investigated the association between IL-18-137, -607 polymorphisms and risk of breast cancer and a possible interaction between the 2 single nucleotide polymorphisms (SNPs) and BMI, menopause in Chinese Han woman.

Methods: A total of 488 participants, including 178 patients with breast cancer, 150 patients with benign breast disease and 160 healthy controls were recruited for this study. Polymerase chain reaction (PCR)-direct sequencing technology was used to identify the genotypes.

Results: 137 G/C genotype can decrease the risk of breast cancer (OR = 0.54, 95% CI: 0.31-0.93; P = .025). In benign group, subjects with G/C genotype of IL-18-137G/C polymorphism had a 1.89-fold increased risk of developing breast cancer (95% CI = 1.05-3.41; P = .032). Among postmenopausal subjects, people with G/T genotype of IL-18-607 polymorphism had a 7.97-fold increased risk of lymph node metastasis compared with those with T/T homozygotes (95% CI = 1.95-32.65; P = .0045). Among Overweight and obese patients with breast cancer (BMI ≥ 24), people with G/T genotype of IL-18-607 polymorphism had a 5.45-fold increased risk of lymph node metastasis compared with those with T/T homozygotes (95% CI = 1.74-17.06; P = .034).

Conclusions: IL-18-137 G/C genotype may be a protective factor for healthy group, but a risk factor for benign group. IL-18-607 G/T genotype have an interaction with menopausal and BMI. The synergetic effect can further increase the risk of lymph node metastasis for breast cancer patients.

Keywords: breast cancer; interleukin-18; polymorphism; susceptibility.

MeSH terms

  • Adolescent
  • Adult
  • Asian People / ethnology
  • Asian People / genetics
  • Breast Neoplasms / blood
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Interleukin-18 / blood
  • Interleukin-18 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Retrospective Studies
  • Young Adult

Substances

  • Interleukin-18