Dataset Information

The prognostic value of four interleukin-1 gene polymorphisms in Caucasian women with breast cancer: a multicenter study.

ABSTRACT:

Background

The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.

Methods

We studied the influence of four common gene polymorphisms (IL1A -889C/T, IL1B -511C/T, IL1B +3953E1/E2, and IL1RN long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.

Results

In the present study 38 cases of cancer related death and a median time of follow-up (range) of 55.3 (0.4-175.8) months was observed. IL1RN 2/2 (homozygous mutant) gene polymorphism was associated with shortened disease free and overall survival in a univariate (p = 0.001 and p = 0.01, respectively) and multivariate analysis (p = 0.002, Odds Ratio [95% Confidence Interval] = 3.6 [1.6-8.0] and p = 0.05, Odds Ratio = 3.0 [1.1-9.3], respectively). Presence of the homozygous mutant genotype of the IL1A -889 and IL1B +3953 gene polymorphism was associated with overall survival in the univariate (p = 0.004 and p = 0.002, respectively), but not in the multivariate analysis. No association was observed between all possible haplotype combinations and overall survival.

Conclusion

Carriage of the mutant alleles of IL1RN was independently associated with shortened disease free and overall survival rates in Caucasian patients with breast cancer.

SUBMITTER: Grimm C

PROVIDER: S-EPMC2656545 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

The prognostic value of four interleukin-1 gene polymorphisms in Caucasian women with breast cancer: a multicenter study.

Grimm Christoph C Kantelhardt Eva E Heinze Georg G Polterauer Stephan S Zeillinger Robert R Kölbl Heinz H Reinthaller Alexander A Hefler Lukas L

BMC cancer 20090306

<h4>Background</h4>The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.<h4>Methods</h4>We studied the influence of four common gene polymorphisms (IL1A -889C/T, IL1B -511C/T, IL1B +3953E1/E2, and IL1RN long/2) of the IL-1 family on survival ...[more]

PMID: 19267917

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Project description:BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and methodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan-Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33-2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

Project description:SummaryThree genes, including EGFR (epidermal growth factor receptor), CALM3 (calmodulin 3, calcium-modulated protein 3) and SMARCD1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily d member 1), play different roles in bone and/or fat metabolism in Caucasian women. In this population-based investigation of 870 unrelated postmenopausal Caucasian women, CALM3 polymorphisms were significantly associated with femoral neck bone mineral density (FNK BMD), hip BMD and spine BMD. Age and tobacco status also affected BMD levels and were therefore corrected for in our statistical analysis.IntroductionEGFR, CALM3 and SMARCD1 play roles in bone and/or fat metabolism. However, the correlations between the polymorphisms of these three genes and body composition levels, including BMD, remain to be determined.Materials and methodsA population-based investigation of 870 white women was conducted. Forty-four SNPs (single nucleotide polymorphisms) in EGFR, CALM3 and SMARCD1 were chosen by the software, including those of potential functional importance. The candidate SNPs were genotyped by the KASPar assay for an association analysis with body composition levels. The correlation analysis was assessed by the Pearson's product-moment correlation coefficient and Spearman rank-order correlation tests, and the family-wise error was corrected using the Wald test implemented in PLINK.ResultsThe SNP rs12461917 in the 3'-flanking region of the CALM3 gene was significantly associated with FNK BMD (P?=?0.001), hip BMD (P<0.001) and spine BMD (P?=?0.001); rs11083838 in the 5'-flanking region of CALM3 gene was associated with spine BMD (P?=?0.009). After adjusting for multiple comparisons, rs12461917 remained significant (P-adjusted?=?0.033 for FNK BMD, P-adjusted?=?0.006 for hip BMD and P-adjusted?=?0.018 for spine BMD).ConclusionsOur data show that polymorphisms of the CALM3 gene in Caucasian women may contribute to variations in the BMD of the hip, spine and femoral neck.

Dataset Information

The prognostic value of four interleukin-1 gene polymorphisms in Caucasian women with breast cancer: a multicenter study.

Background

Methods

Results

Conclusion

Publications

The prognostic value of four interleukin-1 gene polymorphisms in Caucasian women with breast cancer: a multicenter study.

Similar Datasets

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