title: The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients.
abstract: BACKGROUND
  Interleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients.
  
  
  RESULTS
  We genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤ 50 years old at the time of diagnosis, for interleukin 10 -592A > C, -819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 - 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 - 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 - 21.243).
  
  
  CONCLUSIONS
  According to our data, IL10 -1082A > G, -819 T > C, -592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.
authors.affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. erikakorobeinikova@gmail.com.
authors.forename: Erika
authors.initials: E
authors.lastname: Korobeinikova
authors.affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. danamrz@mail.ru.
authors.forename: Dana
authors.initials: D
authors.lastname: Myrzaliyeva
authors.affiliation: Oncology Research Laboratory, Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. rasaugenskiene@gmail.com.
authors.forename: Rasa
authors.initials: R
authors.lastname: Ugenskiene
authors.affiliation: Oncology Research Laboratory, Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. danguoleraulinaityte@gmail.com.
authors.forename: Danguole
authors.initials: D
authors.lastname: Raulinaityte
authors.affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. jurgitagedminaite@yahoo.com.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Gedminaite
authors.affiliation: Health Research Institute, Lithuanian University of Health Sciences, Betonuotoju str. 4-9, LT-52371, Kaunas, Lithuania. kastsmig@gmail.com.
authors.forename: Kastytis
authors.initials: K
authors.lastname: Smigelskas
authors.affiliation: Oncology Institute, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania. elona.juozaityte@kaunoklinikos.lt.
authors.forename: Elona
authors.initials: E
authors.lastname: Juozaityte
mesh_terms: D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D011379:Prognosis; D011446:Prospective Studies; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10