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Polymorphisms in immune mediators associate with risk of cervical cancer.

ABSTRACT: 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.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.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).Our results suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This association should be investigated in additional cervical cancer populations.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC4198466 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Polymorphisms in immune mediators associate with risk of cervical cancer.

Zhang Zhengyan Z Fye Samantha S Borecki Ingrid B IB Rader Janet S JS

Gynecologic oncology 20140812 1

<h4>Objective</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 25127987

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Project description:OBJECTIVES:Studies have suggested that polymorphisms in genes involved in immune recognition and antigen presentation are associated with cervical cancer risk. We sought to replicate a recent study which reported an association between specific SNPs on CD83 and cervical cancer and to further explore whether effects varied by age, clinical stage (in situ versus invasive), and histology (squamous carcinomas versus adenocarcinomas). METHODS:We evaluated the association between SNPs on CD83 and cervical cancer in a multicenter case-control study of cervical cancer conducted in the Eastern United States (263 cases, 307 controls), focusing on the five SNPs (RS9296925, RS853360, RS9230, RS9370729, RS750749) previously found to be associated with cervical cancer. We also pooled data from the Eastern U.S. (263 cases) with those from the original report (377 cases) to assess the effects of CD83 on the age at diagnosis, disease stage, and histology. Risk estimates (ORs) and 95% confidence intervals were estimated using logistic regression; trend tests were performed under an additive model. RESULTS:Consistent with the original report, carriers of the CT or CC genotypes for one of the five CD83 SNPs evaluated (rs750749) demonstrated a 30% and 50% reduction in disease risk, relative to carriers of the more common TT genotype (p-trend=0.02). Two additional SNPs also resulted in consistent findings (rs9296925: p-trend=0.07 and rs9370729: p-trend=0.08), although the effects observed did not reach statistical significance at the 0.05 level. Pooled evaluation of cases from the two aforementioned studies suggested differences in the distribution of susceptibility alleles by histology; adenocarcinoma cases were more likely to be carriers of the susceptibility alleles for SNP rs9370729 (p-trend=0.02) and SNP rs750749 (p-trend=0.09). No differences were observed in the age or stage of diagnosis of carriers for CD83 susceptibility alleles relative to non-carriers. CONCLUSIONS:We confirm an association between CD83 polymorphisms and cervical cancer and suggest the possibility that CD83-disease associations might be heterogenous by tumor histology.

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Polymorphisms in immune mediators associate with risk of cervical cancer.

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Polymorphisms in immune mediators associate with risk of cervical cancer.

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