Biomedical subjects

Jane C Figueiredo

Publications and source records attributed to Jane C Figueiredo.

5 recordsLinked to original sources

PubMed2026

Epigenetic aging of colorectal mucosa in cancer development.

BACKGROUND: The past decade has seen the development of epigenetic models of aging that accurately estimate chronological age and predict disease incidence and mortality. These estimates are modulated by lifestyle and environmental factors linked to carcinogenesis, but to date this has primarily been studied in blood. METHODS: We examined epigenetic aging in normal colonic tissue (n = 96), adjacent mucosa (n = 245) and tumors (n = 208), using models trained on age (Horvath, Hannum, Zhang), mortality (PhenoAge, GrimAge), aging rate (DunedinPACE), cellular mitotic history (EpiTOC, epiTOC2, miAGe), and telomere length (DNAmTL). RESULTS: The Horvath model was the most accurate estimator of chronological age in normal colonic mucosa, with high correlation (r > 0.70) between the Horvath, Hannum, Zhang, PhenoAge and GrimAge models, and between mitotic clocks (r > 0.94). All models showed similar performance in normal tissue and adjacent mucosa, but substantially more variation in estimates in tumors. Significant differences in age acceleration were present between normal and adjacent mucosa by six models (Hannum, Zhang, PhenoAge, EpiTOC, epiTOC2 and miAge), while tumors showed highly significant differences by all models. Age acceleration differed by region of the colon, with varying patterns by model type. Physical activity (PhenoAge), smoking history (GrimAge), and alcohol consumption (Horvath, mitotic clocks) were associated with epigenetic aging in adjacent mucosa, while smoking history, smoking intensity, and alcohol consumption were associated with DNAmTL in tumors. CONCLUSIONS: Our study reveals an impact of tissue type, region, and lifestyle factors on epigenetic aging, but also highlights significant heterogeneity between models and the need for careful consideration within study design.

DNA methylation↗

PubMed2026

MyGeneRisk Colon: A Web-Based Tool for Personalized Colorectal Cancer Risk Prediction Based on Genetics and Lifestyle.

Colorectal cancer (CRC) is a leading cause of cancer-related death, with incidence rising substantially among individuals under 50 years of age. Polygenic risk scores (PRS) hold promise for identifying high-risk individuals; when combined with lifestyle factors, they substantially improve prediction accuracy compared with models based on lifestyle factors alone. However, few clinical tools currently exist that facilitate this integrated, PRS-enhanced risk assessment. To bridge this gap, we developed MyGeneRisk Colo n, a publicly accessible web portal that delivers individualized CRC risk prediction by incorporating genetic, demographic, family history, and lifestyle factors. This paper details the development of the underlying risk prediction model, the portal's architecture and data security, our reporting framework, and engagement with a community advisory panel. Designed as a user-friendly platform, MyGeneRisk Colon aims to effectively communicate personalized CRC risk profiles and educate users and healthcare providers about prevention strategies.

Journal Article↗

PubMed2025

DNA damage repair gene alterations influence the tumor immune microenvironment in advanced non-small cell lung cancer.

PURPOSE: DNA damage response and repair (DDR) gene alterations contribute to genomic instability and increased tumor immunogenicity, yet their clinical significance in non-small cell lung cancer (NSCLC) remains unclear. Using a large real-world dataset, we evaluated the prevalence of DDR alterations and their relation to the tumor immune microenvironment in metastatic NSCLC. EXPERIMENTAL DESIGN: We retrospectively analyzed real-world data from patients with metastatic NSCLC using the Tempus AI database. Tumors were sequenced with Tempus xT DNA and xR RNA assays and classified based on the presence (DDRmt) or absence (DDRwt) of a pathogenic somatic alteration or copy number deletion in a DDR pathway gene. Associations between DDR alterations and immune cell infiltration, PD-L1 immunohistochemistry, tumor mutational burden (TMB), and microsatellite instability (MSI-H) were examined. RESULTS: Among 14,127 patients (median age = 67, 49% female), 5,276 (37%) were DDRmt. There was a higher prevalence of current/former smokers in the DDRmt group (86% vs. 82%; p<0.001). DDRmt tumors were more likely to have higher levels of TMB (median: 5.4 vs. 4.6; p<0.001), MSI-H (1.1 % vs. <0.1 %; p<0.001), and infiltrating CD8+ T cells (p=0.003) compared to DDRwt tumors. A lower frequency of macrophages (p<0.001) were observed among DDRmt compared with DDRwt tumors with no difference in PDL1 positivity. CONCLUSIONS: Among patients with metastatic NSCLC, 37% present with DDRmt tumors characterized by higher TMB, frequency of MSI-H, and changes in immune cell infiltrates. These findings provide insight into the immunogenic landscape of DDR-altered NSCLC and may inform biomarker selection and therapeutic strategies.

Humans↗

PubMed2004

Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry.

This study investigates the role of two nonsynonymous single nucleotide polymorphisms in DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1)-R399Q and X-ray repair cross-complementing group 3 (XRCC3)-T241M, in breast cancer. Incident cases of invasive breast cancer in Caucasian women [n = 402, mean age = 45.7 (SD = 6.2) years] and female Caucasian controls [n = 402, mean age = 45.2 (6.5) years] frequency matched on 5-year age intervals were identified from the Ontario Familial Breast Cancer Registry. No evidence for a main effect of the XRCC1-R399Q genotype on breast cancer risk was observed. Estimates of risk for a family history (FH) of breast cancer compared with no FH differed by XRCC1-R399Q genotype (P value for interaction = 0.001). Homozygote XRCC1-399 R/R individuals and FH+ were at a 2.92-fold [95% confidence interval (95% CI) = 1.47-5.79] increased risk of disease compared with FH- individuals; the estimate of risk increased for R/Q heterozygotes with FH+ [odds ratio (OR) = 3.85, 95% CI = 1.94-7.65] but not for Q/Q homozygotes with FH+ (OR = 0.54, 95% CI = 0.20-1.47) compared with homozygous R/R and FH- individuals. A marginal positive association for XRCC3-241 M/M compared with T/T genotype was found (OR = 1.44, 95% CI = 0.94-2.19), but the heterozygous T/M was not associated with an increase in risk (OR = 0.96, 95% CI = 0.71-1.32). There was also some evidence for a combined effect of body mass index and XRCC3-T241M on estimates of risk. Our results suggest that these polymorphisms may influence breast cancer risk by modifying the effect of risk factors such as FH. There is a need for further study into the role of these polymorphisms as effect modifiers.

Adult↗

PubMed2002

The effect of blindness on horizontal plane sound source identification.

The effect of blindness on sound source identification was studied. Four groups of normally-hearing adults, two sighted and two blind, participated. Subjects were tested using arrays of four and eight loudspeakers, surrounding them in the horizontal plane. One sighted group was tested in quiet. The other groups were tested in continuous 60-dB SPL white noise. Three 75-dB SPL 300-ms stimuli were localized: one-third octave noise bands, centered at 0.5 and 4 kHz, and broadband noise. Broadband noise was easiest to localize (both binaural and spectral cues available), and the 0.5-kHz noise band was the most difficult (primarily interaural temporal difference cue available). Subjects with late-onset blindness achieved significantly higher scores than the early blind and blindfolded sighted subjects. The percentage correct decreased with an increase in the number of speakers, but background noise had no effect. The results attest to the benefit of early visual experience for spatial hearing in adulthood, and demonstrate the negative impact of sudden loss of sight.

Adult↗