PLSD

PLSD provides prospectively observed empirical incidence and survival data for individuals with pathogenic variants in mismatch repair genes (path_MMR) to support evidence-based assessment of cancer risks and outcomes.

Key Features:

• Prospective incidence and survival data: Provides prospectively observed incidence of cancers across multiple organs and survival rates following cancer diagnoses among path_MMR carriers.
• Stratified reporting: Stratifies data by age, specific MMR gene, and gender.
• Intervention impact analysis: Reports the impact of medical interventions, including colonoscopic surveillance frequency, on cancer incidence and survival.
• Assumption-free approach: Applies an assumption-free approach based on observed outcomes rather than theoretical models.
• Ascertainment/selection bias declaration: Identifies and requires declaration of potential ascertainment or selection biases introduced by cohort recruitment.
• Gene-specific syndrome characterization: Identifies distinct multi-cancer syndromes with gene-specific penetrance and phenotypic profiles across different MMR variants.
• Subsequent malignancy detection: Detects subsequent primary malignancies and their contributions to cancer-related mortality among survivors.
• Integration with variant databases: Integrates variant data from the InSiGHT database.

Scientific Applications:

• Genetic counseling and risk estimation: Enables evidence-based risk estimates for individuals with path_MMR variants to inform genetic counseling.
• Surveillance strategy evaluation: Evaluates effectiveness of surveillance strategies, including colonoscopic screening frequency, on colorectal cancer incidence and outcomes.
• Clinical decision support for treatment and survivorship: Informs treatment strategies and survivorship management by providing survival and subsequent-malignancy data.
• Carcinogenetic mechanisms research: Supports research into carcinogenetic mechanisms by providing empirical, multi-organ incidence and survival data stratified by gene.
• Variant penetrance and phenotype research: Facilitates characterization of variant-specific penetrance and phenotypic expression across MMR genes.

Methodology:

Analyzes prospectively collected observational data using an assumption-free approach, stratifying incidence and survival by age, MMR gene, and gender, integrating InSiGHT variant database entries, and identifying declared ascertainment/selection biases.