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Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.

ABSTRACT: Human papillomavirus is the acknowledged cause of cervical cancer. We hypothesized that allergies, characterized by hyperimmune reaction to common allergens and which have been associated with various cancers, may be related to cervical cancer, and that genetic variation in cytokine genes related to allergies might impact cervical cancer risk.We investigated the risk of invasive squamous cell cervical cancer (SCC) associated with self-reported allergies and with variation in allergy-related cytokine genes using data from a case-control study (561 cases, 1,258 controls) conducted in Washington State. Logistic regression models yielded odds ratios (OR) and 95% CI.Pollen allergy, the most commonly reported allergy, was associated with reduced SCC risk (OR: 0.6; 95% CI: 0.5-0.8). Of 60 tagging single-nucleotide polymorphisms covering eight genes (CSF2, IL3, IL4, IL13, CSF2RB, IL4R, IL13RA1, IL13RA2), several were related to pollen allergies among controls: IL4R rs3024647 (dominant OR: 1.5; 95% CI: 1.0-2.3; P = 0.04), CSF2RB rs16997517 (dominant OR: 2.2; 95% CI: 1.0-4.7; P = 0.04), and IL13 rs1800925 (per-allele OR: 1.7; 95% CI: 1.3-2.4; P = 0.0007). Two variants were inversely associated with SCC risk: IL4R rs3024656 (per-allele OR: 0.8; 95% CI: 0.6-1.0; P = 0.03) and CSF2RB rs16997517 (dominant OR: 0.4; 95% CI: 0.2-0.9; P = 0.04).Pollen allergies were related to reduced SCC risk. CSF2RB rs16997517 was directly related to pollen allergies in controls and to reduced SCC risk.If other studies confirm these results, the mechanism behind allergy-associated immune response associated with SCC risk may be worth exploring in the context of therapeutic or prophylactic vaccines.

SUBMITTER: Johnson LG

PROVIDER: S-EPMC3057941 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.

Johnson Lisa G LG Schwartz Stephen M SM Malkki Mari M Du Qin Q Petersdorf Effie W EW Galloway Denise A DA Madeleine Margaret M MM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20101111 1

<h4>Background</h4>Human papillomavirus is the acknowledged cause of cervical cancer. We hypothesized that allergies, characterized by hyperimmune reaction to common allergens and which have been associated with various cancers, may be related to cervical cancer, and that genetic variation in cytokine genes related to allergies might impact cervical cancer risk.<h4>Methods</h4>We investigated the risk of invasive squamous cell cervical cancer (SCC) associated with self-reported allergies and wit ...[more]

PMID: 21071541

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Project description:ObjectivesStudies 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).MethodsWe 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.ResultsConsistent 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.ConclusionsWe confirm an association between CD83 polymorphisms and cervical cancer and suggest the possibility that CD83-disease associations might be heterogenous by tumor histology.

Project description:In this report, we describe a case control study in a Chinese population aimed at identifying possible associations between susceptibility to cervical cancer and single nucleotide polymorphisms in XRCC1 194C>T, XRCC1 280G>A, XRCC1 399G>A, ERCC2 751A>C, ERCC2 156C>A, ERCC1 118C>T, PARP1 762T>C, RAD51 135G>C and HER2 655A>G. The cases comprised 154 patients: 80 cervical squamous cell carcinomas (SCCs), 2 adenocarcinomas and 72 cervical intraepithelial neoplasias (CINs). A total of 177 healthy women were recruited as the controls. A significant association was found between ERCC1 118C>T and SCC in the additive genetic model [odds ratio (OR)=1.711; 95% confidence interval (CI), 1.089-2.880; p=0.021] and the dominant genetic model (OR=1.947; 95% CI, 1.056-3.590; p=0.033). Among women with a smoking family member, ERCC1 118C>T increased SCC risk in the additive model (OR=2.800; 95% CI, 1.314-5.968; p=0.008). For women who had first intercourse before 22 years of age, XRCC1 280G>A was found to act as a protective factor for SCC under the additive model (OR=0.228; 95% CI, 0.058-0.900; p=0.035), while RAD51 135G>C was a risk factor for CIN (OR=4.246; 95% CI, 1.335-13.502; p=0.014). For women who had first intercourse after 22 years of age, the additive genetic model showed RAD51 135G>C (OR=0.359; 95% CI, 0.138-0.934; p=0.036) and HER2 655A>G (OR=0.309; 95% CI, 0.098-0.972; p=0.045) to be protective factors for SCC. XRCC1 399G>A increased CIN risk among women who first gave birth before the age of 22 in the additive genetic model (OR=4.459; 95% CI, 1.139-17.453; p=0.032). For those who first gave birth after age 22, ERCC1 118C>T was found to be a risk factor for SCC in the additive genetic model (OR=1.884; 95% CI, 1.088-3.264; p=0.024). A significant interaction was observed between RAD51 135G>C and age at first intercourse (p(interaction)=0.033 for SCC, p(interaction)=0.021 for CIN), as well with sexual partner number (p(interaction)=0.001 for SCC). The interaction between HER2 655A>G and age at first intercourse, ERCC2 156C>A and family smoking status and XRCC1 280G>A and alcohol consumption were significant, with p(interaction)=0.023 for SCC, p(interaction)=0.021 for CIN and p(interaction)=0.025 for SCC, respectively.

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Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.

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Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.

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