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Joint effects of febrile acute infection and an interferon-? polymorphism on breast cancer risk.

ABSTRACT: BACKGROUND: There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-?) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-? may modify the association of febrile infection with breast cancer risk. METHODOLOGY AND PRINCIPAL FINDINGS: Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-? (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ?1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61-0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37-0.77)] but not in those with the CC genotype [1.09 (0.77-1.55)]. The association of IFN-? rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03-1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40-0.99)] among women with ?1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-? genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively). CONCLUSIONS: Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-? rs2069705.

SUBMITTER: Su Y

PROVIDER: S-EPMC3356273 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Joint effects of febrile acute infection and an interferon-γ polymorphism on breast cancer risk.

Su Yi Y Tang Lu-Ying LY Chen Li-Juan LJ He Jian-Rong JR Su Feng-Xi FX Lin Ying Y Chen Wei-Qing WQ Xie Xiao-Ming XM Ren Ze-Fang ZF

PloS one 20120518 5

<h4>Background</h4>There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk.<h4>Methodology and principal findings</h4>Information on potential breast cancer risk factors, history of fever during the last 10 y ...[more]

PMID: 22624006

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Project description:Introduction:Breast cancer is the most common type of cancer among women. In Kazakhstan, breast cancer holds first place among causes of women death caused by cancer in the 45-55 year age group. Many studies have shown that the risk of acquiring breast cancer may be related to the level of calcium in the blood serum. One of the important regulators of calcium metabolism in the body is the parathyroid hormone. Single nucleotide polymorphisms in the gene encoding the parathyroid hormone (PTH) are associated with breast cancer development risk, and may modify the associative interaction between the levels of calcium intake and breast cancer. Experimental studies have shown that PTH gene has a carcinogenic effect. At least three studies showed a weak positive correlation between the risk of acquiring breast cancer and primary hyperparathyroidism, a state with high levels of PTH and often high levels of calcium. The aim of this investigation was to evaluate potential association between PTH gene polymorphism and breast cancer risk among Kazakhstani women. Methods:Female breast cancer patients (n = 429) and matched control women (n = 373) were recruited into a case - control study,. Genomic DNA was extracted from peripheral venous blood of study participants using Wizard® Genomic DNA Purification Kit (Promega, USA). Detection of PTH gene polymorphism (rs1459015) was done by means of the TaqMan® SNP Genotyping Assay of real-time PCR. Statistical analysis was conducted using SPSS 19.0. Results:PTH gene alleles were in Hardy-Weinberg equilibrium (p > 0.05). Distribution was 59% CC, 35% CT, 6% TT in the group with breast cancer and 50% CC, 43% CT, 6% TT in the control group. Total difference (between the group with breast cancer and the control group) in allele frequencies for PTH polymorphism was not significant (p > 0.05). No association was found between rs1459015 TT and breast cancer risk (OR = 1.039; 95%, CI 0.740 - 1.297; p = 0.893). Conclusion:We found no association between PTHrs1459015 polymorphism and breast cancer in our present study. Further studies are required to confirm our results and clarify role of PTH gene genotypes on breast cancer risk.

Project description:Background:Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors. Methods:Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status. Results:The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction?=?0.009), adult height (P-interaction?=?0.025) and current use of combined MHT (P-interaction?=?0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P?=?0.013 for global and 0.18 for tail-based tests). Conclusions:The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.

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Dataset Information

Joint effects of febrile acute infection and an interferon-? polymorphism on breast cancer risk.

Publications

Joint effects of febrile acute infection and an interferon-γ polymorphism on breast cancer risk.

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