Our findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake.
Background: Shorter telomere length (TL) has been reported to be associated with increased risk of early death in elder individuals. Telomere shortening has been also related to chromosomal instability, which may possibly contribute to the development of several types of digestive or urogenital system cancers and smokingrelated tumors. Therefore, we investigated the impact of TL on bladder cancer survival.Methods: TL was measured in leukocyte DNA from whole peripheral blood using quantitative real-time PCR in 463 patients with bladder cancer from a total 726 cases who were followed for up to 18 years.Results: Patients with muscle-invasive tumor/any grade had shorter telomere than patients with nonmuscle-invasive tumor/high-grade and with non-muscle-invasive tumor/non-high-grade (TL reference 0.7 AE 0.2; vs. respectively, 0.8 AE 0.2, P ¼ 3.4 Â 10 À2 and 0.8 AE 0.2, P ¼ 3.6 Â 10
Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B‐cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case–control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p = 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2–4, respectively, p‐trend = 0.001], diffuse large B‐cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2–4, respectively, p‐trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2–4, respectively, p‐trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.
In Europe, bladder cancer (BC) is the sixth most commonly diagnosed tumor and the second most common cause of death among patients with genitourinary tract malignancies. The ability to repair DNA damage is strongly associated with the risk of cancer and inter-individual variation in DNA repair capacity (DRC) might account for different susceptibility of developing cancer. DRC represents a complex marker comprising the sum of several factors such as gene variants, gene expression, stability of gene products, and effect of inhibitors/stimulators. Individuals with low DRC will tend to accumulate more damage than those who have a better ability to repair such damage. This variability is modulated by the genetic background to which SNPs/haplotype combinations in DNA repair genes, as well as epigenetic regulation are likely to contribute. Phenotypic assays to evaluate DNA repair activity (in particular NER comet assay, H2AX phosphorylation and micronucleus assay) were performed on cryopreserved lymphocytes from 159 cases (collected before treatment) and 159 controls matched by age and smoking habits, enrolled in Turin Bladder Cancer Study (TBCS). We aimed at studying the relationship between DRC (evaluated by comet assay, micronuclei and H2AX phosphorylation assay) and bladder cancer integrating, gene expression and epigenetic profile data (methylation levels and microRNA expression). In particular, we performed an integrated analysis on the genotype/phenotype correlation in a population of bladder cancer cases and controls provided with detailed description of the follow-up for response to therapy/recurrence/survival. This integrated approach will help in elucidating the role of DRC (and its determinants) as predictive and prognostic marker and to identify combined biomarkers to be measured in blood cells as non-invasive predictive method.
Citation Format: Barbara Pardini, Alessandra Allione, Simonetta Guarrera, Valentina Turinetto, Giovanni Fiorito, Fabio Rosa, Alessia Russo, Federica Modica, Claudia Giachino, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo. DNA repair capacity, gene expression and epigenomic profiles in bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5367. doi:10.1158/1538-7445.AM2014-5367
<p>Supplementary Table S3. Multivariate Cox regression survival analysis, including TL, age, TG, BCG, radical cystectomy, radiotherapy and chemotherapy. All cause of death.</p>
<p>Supplementary Figure S1. Kaplan-Meier OS curves of bladder cancer patients stratified for TL quartiles. OS, overall survival; TL, telomere length.</p>
<p>Supplementary Table S3. Multivariate Cox regression survival analysis, including TL, age, TG, BCG, radical cystectomy, radiotherapy and chemotherapy. All cause of death.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.