title: Significant association of combination of OCT4, NANOG, and SOX2 gene polymorphisms in susceptibility and response to treatment in North Indian breast cancer patients.
abstract: OBJECTIVE
  Dysregulations of regulatory genes in embryonic stem cells (ESCs) gene polymorphisms may lead to breast cancer cell growth, differentiation, and tumor metastasis.
  
  
  METHODS
  Polymorphisms in OCT4 (rs3130932), NANOG (rs11055786), LIN28 (rs4274112), and SOX2 (rs11915160) genes were evaluated for susceptibility in 297 breast cancer females and 273 healthy controls from north Indian population. Response to neo-adjuvant chemotherapy was followed in 128 locally advanced breast cancer patients along with clinicopathological features. Genotyping was done using TaqMan allelic discrimination assays. Statistical analysis was performed using SPSS and multifactor dimensionality reduction (MDR).
  
  
  RESULTS
  For OCT4 gene polymorphism, protective effect of genotypes AC [P corr = 0.031, OR = 0.63 (0.44-0.91)] and AC+CC [P corr = 0.031, OR = 0.68 (0.48-0.95)] was seen in patients. However, no association of NANOG, LIN28, and SOX2 gene polymorphisms was found with overall breast cancer susceptibility. Further, significant association of AG+GG genotype [P corr = 0.021, OR = 6.08 (1.83-20.15)] and G allele [P corr = 0.021, OR = 3.07 (1.21-7.77)] of rs4274112 polymorphism was seen with positive lymph node. For OCT4, significant association of allele C was seen with patients having negative hormone receptor [P corr = 0.021, OR = 0.51 (0.29-0.90)], but no association of any of the studied polymorphisms individually was found with response to NACT. On MDR analysis, we found combination of SNPs SOX2 rs11915160, OCT4 rs3130932, and NANOG rs11055786 to be the best interaction model for predicting breast cancer risk [p for permutation test <10(-3), OR = 2.04 (1.43-2.910] and response to NACT [p for permutation test = 0.005, OR = 2.09 (1.24-3.52)].
  
  
  CONCLUSIONS
  Combination of genetic variants of ESCs gene may have a profound effect in breast cancer risk and response to NACT.
authors.affiliation: Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli road, Lucknow, 226 014, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Tulsyan
authors.forename: Gaurav
authors.initials: G
authors.lastname: Agarwal
authors.forename: Punita
authors.initials: P
authors.lastname: Lal
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D020360:Neoadjuvant Therapy; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps; D012307:Risk Factors; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors