title: Polymorphisms in immune mediators associate with risk of cervical cancer.
abstract: OBJECTIVE
  The immune system is critical for controlling the progression of HPV cervical disease and the development of cancer. This study aimed to identify cervical cancer susceptibility alleles in candidate immune-modulating genes.
  
  
  METHODS
  Our family-based study involved a cohort of 641 probands (women with ICC/CIN III) and their biologic parents or siblings (641 trios). In the discovery phase (stage 1), involving 288 of the trios, 80 tag single nucleotide polymorphisms (SNPs) in 11 immune-modulating genes (IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1, STAT6, IL12A, TNF, LTA and LTB) were evaluated on the GoldenGate platform. We used the combined dataset for a total of 641 trios (stage 2) and the Taqman platform to validate the SNPs that had proved significant in the discovery dataset. The transmission disequilibrium test was used to detect significant shifts in allelic transmissions in the datasets.
  
  
  RESULTS
  Two SNPs in JAK2 and one SNP in STAT6 showed significant allelic association with cervical cancer in the stage 1 discovery dataset and were replicated in the larger joint analysis stage 2 dataset (JAK2 rs10815144, P=0.0029 and rs12349785, P=0.0058; and STAT6 rs3024971, P=0.0127). An additional SNP in exon 19 of JAK2 (rs2230724) was also examined in the combined dataset due to its strong linkage disequilibrium (LD) with rs10815144. It was also significant (P=0.0335).
  
  
  CONCLUSIONS
  Our results suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This association should be investigated in additional cervical cancer populations.
authors.affiliation: Washington University School of Medicine in St. Louis, 660 South Euclid Ave., St. Louis, MO 63011, USA.
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Medical College of Wisconsin, 9200W. Wisconsin Ave., Milwaukee, WI 53226, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Fye
authors.affiliation: Washington University School of Medicine in St. Louis, 660 South Euclid Ave., St. Louis, MO 63011, USA.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Medical College of Wisconsin, 9200W. Wisconsin Ave., Milwaukee, WI 53226, USA. Electronic address: jrader@mcw.edu.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rader
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology*
chemical_list: D007155:Immunologic Factors
keywords: Cervical cancer; JAK2; STAT6; Single nucleotide polymorphisms