bims-ovdlit 2024-03-03 papers

Issue of 2024‒03‒03
three papers selected by
Lara Paracchini, Humanitas Research

Clin Epigenetics. 2024 Feb 27. 16(1): 34

Prediction of methylation status using WGS data of plasma cfDNA for multi-cancer early detection (MCED).

Pin Cui, Xiaozhou Zhou, Shu Xu, Weihuang He, Guozeng Huang, Yong Xiong, Chuxin Zhang, Tingmin Chang, Mingji Feng, Hanming Lai, Yi Pan.

BACKGROUND: Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on cfDNA fragmentation patterns. We performed whole-genome bisulfite sequencing and whole-genome sequencing (WGS) on both healthy individuals and cancer patients. Using the information of whole-genome methylation levels, we investigated cytosine-phosphate-guanine (CpG) cleavage profile and validated the method of predicting the methylation level of individual CpG sites using WGS data.RESULTS: We conducted CpG cleavage profile biomarker analysis on data from both healthy individuals and cancer patients. We obtained unique or shared potential biomarkers for each group and built models accordingly. The modeling results proved the feasibility to predict the methylation status of single CpG sites in cfDNA using cleavage profile model from WGS data.
CONCLUSION: By combining cfDNA cleavage profile of CpG sites with machine learning algorithms, we have identified specific CpG cleavage profile as biomarkers to predict the methylation status of individual CpG sites. Therefore, methylation profile, a widely used epigenetic biomarker, can be obtained from a single WGS assay for MCED.

Keywords: Methylation status; Multi-cancer early detection; WGBS; WGS; cfDNA fragmentation profile

DOI: https://doi.org/10.1186/s13148-024-01646-6

JAMA Oncol. 2024 Feb 29.

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Hereditary Breast Cancer Clinical Study Group

Importance: Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.Objective: To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.
Design, Setting, and Participants: In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.
Exposures: Self-reported bilateral oophorectomy (with or without salpingectomy).
Main Outcomes and Measures: All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
Results: There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy.
Conclusions and Relevance: In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

DOI: https://doi.org/10.1001/jamaoncol.2023.6937

J Epidemiol Community Health. 2024 Mar 01. pii: jech-2023-220834. [Epub ahead of print]

Impact of screening participation on modelled mortality benefits of a multi-cancer early detection test by socioeconomic group in England.

Rebecca Smittenaar, Samantha L Quaife, Christian von Wagner, Thomas Higgins, Earl Hubbell, Lennard Lee.

BACKGROUND: Cancer burden is higher and cancer screening participation is lower among individuals living in more socioeconomically deprived areas of England, contributing to worse health outcomes and shorter life expectancy. Owing to higher multi-cancer early detection (MCED) test sensitivity for poor-prognosis cancers and greater cancer burden in groups experiencing greater deprivation, MCED screening programmes may have greater relative benefits in these groups. We modelled potential differential benefits of MCED screening between deprivation groups in England at different levels of screening participation.METHODS: We applied the interception multi-cancer screening model to cancer incidence and survival data made available by the National Cancer Registration and Analysis Service in England to estimate reductions in late-stage diagnoses and cancer mortality from an MCED screening programme by deprivation group across 24 cancer types. We assessed the impact of varying the proportion of people who participated in annual screening in each deprivation group on these estimates.
RESULTS: The modelled benefits of an MCED screening programme were substantial: reductions in late-stage diagnoses were 160 and 274 per 100 000 persons in the least and most deprived groups, respectively. Reductions in cancer mortality were 60 and 99 per 100 000 persons in the least and most deprived groups, respectively. Benefits were greatest in the most deprived group at every participation level and were attenuated with lower screening participation.
CONCLUSIONS: For the greatest possible population benefit and to decrease health inequalities, an MCED implementation strategy should focus on enhancing equitable, informed participation, enabling equal participation across all socioeconomic deprivation groups.
TRIAL REGISTRATION NUMBER: NCT05611632.

Keywords: EPIDEMIOLOGY; HEALTHCARE DISPARITIES; NEOPLASMS; PUBLIC HEALTH; SCREENING

DOI: https://doi.org/10.1136/jech-2023-220834