GSTP1, GSTM1, and GSTT1 polymorphisms as predictors of response to chemotherapy in patients with breast cancer: a meta-analysis

Abstract

Several studies have investigated the effects of polymorphisms in the GSTP1, GSTT1, and GSTM1 genes on responsiveness to chemotherapy in breast cancer, but the results have been inconsistent. The aim of this study was to determine the association between polymorphisms of GSTP1, GSTT1, and GSTM1 genes and response to chemotherapy in patients with breast cancer. The relevant studies were retrieved from PubMed, Embase, ISI Web of Knowledge, China National Knowledge Infrastructure, and Wanfang databases. The articles evaluating the correlations between response to chemotherapy and GSTP1, GSTT1, and GSTM1 polymorphisms in breast cancer patients were comprehensively reviewed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure the strength of the associations. These associations were assessed with the χ ² test in this meta-analysis. Subgroup analysis by chemotherapy protocol and ethnicity were conducted to explore the source of heterogeneity among studies. A total of 14 articles with 31 studies involving GSTP1, GSTT1, and GSTM1 polymorphisms with response to chemotherapy were identified in the final meta-analysis. In the overall analysis, a significant association of GSTM1-present/GSTM1-null polymorphism with responsiveness to chemotherapy was observed in breast cancer patients (OR 0.74, CI 0.60–0.92, P = 0.006), whereas the GSTT1-present/GSTT1-null and GSTP1rs1695 polymorphisms were not significantly associated with clinical response to chemotherapy. The subgroup analysis by chemotherapy protocol indicated that the patients who harboring GSTP1rs1695 AA or AG variant had a higher response rate to anthracycline-based chemotherapy than those carrying GSTP1rs1695 GG variant [AA vs. GG: OR 0.48, CI 0.29–0.80, P < 0.05; AA vs. AG: OR 0.60, CI 0.43–0.83, P < 0.05; A vs. G: OR 0.60, CI 0.47–0.77, P < 0.05; AA vs. (AG + GG): OR 0.56, CI 0.42–0.76, P < 0.05; (AA + AG) vs. GG: OR 0.57, CI 0.34–0.94, P < 0.05]. In addition, the heterogeneity existed among studies for GSTP1 polymorphism, while no obvious heterogeneity was detected for GSTT1 and GSTM1 polymorphisms. And the heterogeneity present in different studies, evaluating the association of GSTP1 polymorphism with response to anthracycline-based chemotherapy, disappeared in breast cancer patients after subgroup analysis by chemotherapy regimen was performed. In conclusion, this meta-analysis suggested that GSTP1rs1695 and GSTM1-present/GSTM1-null polymorphisms could be considered as reliable predictors of response to anthracycline-based chemotherapy in patients with breast cancer.

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Case of anti-RuvBL1/2 antibody-positive morphea and polymyositis

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Usefulness of serum 5-S-cysteinyl-dopa as a biomarker for predicting prognosis and detecting relapse in patients with advanced stage malignant melanoma

Abstract

With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5-S-cysteinyl-dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5-S-cysteinyl-dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0–II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5-S-cysteinyl-dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III–IV), serum 5-S-cysteinyl-dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5-S-cysteinyl-dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs.

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Case with cellulitis, lymphangitis and subcutaneous nodule suspected due to Rickettsia japonica carrying tick bite

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Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case–control study in Taiwan

Abstract

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05–1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36–31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42–5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

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Successful treatment of intractable vulvitis circumscripta plasmacellularis via combination therapy with topical tacrolimus and tetracycline

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The head and neck cancer immune landscape and its immunotherapeutic implications.

Related Articles

The head and neck cancer immune landscape and its immunotherapeutic implications.

JCI Insight. 2016 Oct 20;1(17):e89829

Authors: Mandal R, Şenbabaoğlu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, Lee KW, Ganly I, Hakimi AA, Chan TA, Morris LG

Abstract
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation. We find that both HPV(+) and HPV(-) HNSCC tumors are among the most highly immune-infiltrated cancer types. Strikingly, HNSCC had the highest median Treg/CD8(+) T cell ratio and the highest levels of CD56(dim) NK cell infiltration, in our pan-cancer analysis of the most immune-infiltrated tumors. CD8(+) T cell infiltration and CD56(dim) NK cell infiltration each correlated with superior survival in HNSCC. Tumors harboring genetic smoking signatures had lower immune infiltration and were associated with poorer survival, suggesting these patients may benefit from immune agonist therapy. These findings illuminate the immune landscape of HPV(+) and HPV(-) HNSCC. Additionally, this landscape provides a potentially novel rationale for investigation of agents targeting modulators of Tregs (e.g., CTLA-4, GITR, ICOS, IDO, and VEGFA) and NK cells (e.g., KIR, TIGIT, and 4-1BB) as adjuncts to anti-PD-1 in the treatment of advanced HNSCC.

PMID: 27777979 [PubMed - in process]

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