The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity.
Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed.
Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI).
From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols.
Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.

Tuberculosis is still a global infectious disease. New drugs to shorten the course of treatment and new vaccines are the key points to control tuberculosis. The physiological study of Mycobacteria will contribute to the above-mentioned purposes. Polyphosphate plays an important role in the stress adaptation in bacteria. And there are two classes of enzymes:polyphosphate kinase and exopolyphosphatase involved in the polyphosphate metabolism to control the dynamic equilibrium of polyphosphate level in Mycobacteria. Present paper summarized the progress in metabolism and physiological roles of polyphosphate in Mycobacteria, to provide useful information for studying the physiological function of polyphosphate in Mycobacteria.

Emerging evidence indicates that FHIT is a candidate tumor suppressor in many types of tumors including non-small-cell lung carcinoma (NSCLC). However, the prognostic value and correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In this report, we performed a meta-analysis to evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics of human NSCLC patients. Final analysis of 1,801 NSCLC patients from 18 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue. The pooled odds ratio (OR) from ten studies included 819 NSCLC and 792 normal lung tissues (OR =7.51, 95% confidence interval [CI] =2.98-18.91, P<0.0001). Subgroup analysis based on ethnicity implied that FHIT hypermethylation level was higher in NSCLC tissues than in normal tissues in both Caucasians (P=0.02) and Asians (P<0.0001), indicating that the difference in Asians was much more significant. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. In addition, patients with FHIT hypermethylation had a lower survival rate than those without (hazard ratio =1.73, 95% CI =1.10-2.71, P=0.02). The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and poor survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential diagnostic marker and drug target of NSCLC.

Emerging evidence indicates that FHIT is a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Thus, we conducted a meta-analysis to quantitatively evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 1717 NSCLC patients from 16 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 8 studies including 735 NSCLC and 708 normal lung tissue, OR = 5.45, 95% CI = 2.15-13.79, p = 0.0003. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. We did not find that FHIT hypermethylation was correlated with the differentiated types or clinical stages in NSCLC patients. However, patients with FHIT hypermethylation had a lower survival rate than those without, HR = 1.73, 95% CI = 1.10-2.71, p = 0.02. The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and worsen survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential drug target of NSCLC.

FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.

Research has suggested a link between smoking and cervical cancer; however, little data are available on secondhand smoke (SHS) exposure and cervical cancer risk. This article reviews the literature on the links among smoking, SHS exposure and cervical cancer. The review was based on a search of electronic databases. The research reviewed clearly showed that smoking increases cervical cancer risk through myriad mechanisms that interact with genetics and the pathologic processes leading to cervical cancer. However, less is understood about the role of SHS in cervical cancer. With new technology enabling scientists to examine how genomic structure responds to environmental stimuli, more information should be forthcoming on links between SHS exposure, biomarkers, and genetic changes involved in the development of cervical cancer.

BACKGROUND: The fragile histidine triad gene (FHIT) encompasses a human common fragile site, FRA3B, that is susceptible to environmental carcinogens. Deletion and inactivation of FHIT have been seen in a number of human premalignant and malignant lesions.
OBJECTIVE: To review and evaluate preclinical studies of cancer therapy using the FHIT tumor suppressor gene and related studies involving Fhit protein expression.
METHODS: A MEDLINE search of articles published from 1996 to June 2001 was performed; article reference lists were used to retrieve additional relevant articles.
METHODS: Immunohistochemical studies of primary tumors or relevant lesions were selected to evaluate Fhit expression in premalignant or malignant stages. Preclinical studies on antitumorigenic or therapeutic introduction of FHIT were reviewed for the effects of exogenous Fhit expression. For the immunohistochemical analyses, 26 studies were included that analyzed at least 15 cases of a single type of tumor. For precancerous lesions, 9 studies were included that analyzed at least 4 cases. For studies of FHIT introduction, 9 published studies were included.
METHODS: Using primary data from each of the studies, we assessed the rationale and potential contribution of FHIT cancer therapy. Data was independently abstracted by 2 authors and study quality was assessed by 2 other authors.
RESULTS: Overall, 60% (1162/1948 cases) of primary tumors showed absent or markedly reduced Fhit protein expression in cancer cells. Studies of preneoplastic lesions or early-stage cancer showed absence or marked reduction of Fhit protein expression in 0% to 93% of samples (overall, 31% [127/408 cases]). Preclinical studies using 26 cancer-derived cell lines from human lung, head and neck, esophageal, gastric, cervical, pancreatic, and kidney cancers, showed that reintroduction of FHIT resulted in inhibition of in vitro tumor cell growth or of in vivo tumorigenicity in 17 (57%) of 30 cell line experiments. Model systems for human preventive cancer therapy suggested that oral introduction of viral vector-mediated FHIT into Fhit-deficient mice may prevent carcinogen-induced tumor development in some cases.
CONCLUSIONS: These findings show that FHIT gene therapy may potentially be clinically useful for treatment of cancer and also prevention of carcinogen-induced tumor development, suggesting a rationale for further research involving FHIT introduction.

Chromosomal fragile sites are specific loci which are especially susceptible to forming gaps, breaks and rearrangements in metaphase chromosomes when cells are cultured under conditions that inhibit DNA replication. Fragile sites are grouped into two classes the \'rare\' and the \'common\' fragile sites, based on their frequency of occurrence and means of induction. The common fragile sites are apparently present as a constant feature in all individuals and their clinical significance is that they might predispose chromosomes to breakage and rearrangement during cancer development. The most frequently observed common fragile sites occur, in decreasing order, at 3p14.2 (FRA3B), 16q23 (FRA16D), 6q26 (FRA6E), 7q32 (FRA7H), and Xp22 (FRAXB). FRA3B has been of particular interest since it is the most active common fragile site, and is located in a chromosomal band that is frequently deleted in several solid tumors suggesting that a putative tumor suppressor gene resides there. In this review we describe our work on the characterization of FRA3B and the analysis of deletions in the FRA3B region in several different tumor-derived cell lines. We also describe our efforts to identify other common fragile sites and to determine the role that these sites play in tumor development.

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