title: Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women.
abstract: BACKGROUND
  Cytokines are known as important regulators of the entire gamut of cancer from initiation, invasion and metastasis. This fact and plethora of gene polymorphism data prompted us to investigate cytokine gene polymorphisms in breast cancer (BC) patients.
  
  
  METHODS
  Selected polymorphisms in the IL-1β [-511 T>C (rs16944) and +3954 C>T (rs1143634)]; IL-6 [-174 G>C (rs1800795)]; IL-10 [-1082 A>G (rs1800896), -819 T>C (rs1800871) and -592 A>C (rs1800872)] genes were genotyped in 200 BC patients and 200 healthy volunteers in a case-control study using PCR-RFLP and direct DNA sequencing techniques. Peripheral cytokine levels were measured using ELISA. Allele and genotype data were analyzed for significance of differences between cases and controls using Chi-Square [χ(2)] test. Two sided P-values of less than 0.05 were considered to be statistically significant.
  
  
  RESULTS
  Peripheral level of all three cytokines did not show any significant difference between cases and controls. Allele and genotype frequency of IL-1β [-511 T>C (rs16944)] did not show any difference between cases and controls. On the other hand mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] associated with increased risk of BC. This was also true for pre-menopausal cases and for mutant genotype in post-menopausal cases. Mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] appeared to be protective in nature such that controls had a higher frequency of both mutant alleles and genotypes. None of the three SNPs in IL-10 gene associated with risk of BC, except significant association of mutant allele and genotypes of -1082 A>G (rs1800896) polymorphism with postmenopausal BC.
  
  
  CONCLUSIONS
  Mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] site associated with increased BC risk, while mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] polymorphism appeared to be protective. Also, there was significant association of mutant allele and genotypes of IL-10 [-1082 A>G (rs1800896)] with postmenopausal BC. None of the other polymorphisms investigated appear to affect BC risk.
authors: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors: Singh
authors: S
authors: Pooja
authors: Preeti
authors: P
authors: Chaudhary
authors: Lakshma V
authors: LV
authors: Nayak
authors: Singh
authors: S
authors: Rajender
authors: Karan Singh
authors: KS
authors: Saini
authors: Debashish
authors: D
authors: Deol
authors: Sandeep
authors: S
authors: Kumar
authors: Hemant Kumar
authors: HK
authors: Bid
authors: Rituraj
authors: R
authors: Konwar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016753:Interleukin-10