# Within-family analysis of PRS313: insights into breast cancer risk prediction

## TL;DR

This study explores how a genetic risk score for breast cancer works in an Iranian population, finding it more useful when comparing family members rather than the general population.

## Contribution

The study is the first to evaluate PRS313 in an Iranian population and highlights the importance of within-family analysis for risk prediction.

## Key findings

- PRS313 showed no significant association with breast cancer risk in the general population.
- Significant PRS differences were found between breast cancer patients and their relatives.
- Only one BRCA2 variant was common among breast cancer cases in the cohort.

## Abstract

•First Study Evaluating PRS313 in an Iranian Population•Within-Family PRS Comparison•Lack of Significant Association in General Population•Significant PRS Differences in Family Groups•Importance of Population-Specific PRS Models

First Study Evaluating PRS313 in an Iranian Population

Within-Family PRS Comparison

Lack of Significant Association in General Population

Significant PRS Differences in Family Groups

Importance of Population-Specific PRS Models

Polygenic risk scores (PRS) incorporate numerous genetic variants, each with a small impact on cancer pathogenesis, to provide personalized risk assessments. This study investigated, the applicability of PRS313 for breast cancer risk both in the general population and within families (patients vs different groups of their relatives) from the Tehran Cardiometabolic Genetic Study (TCGS)cohort. The cohort included 72 breast cancer cases and 2,603 controls. PRS313 showed no significant difference between cases and controls, and logistic regression indicated no significant association between PRS313 and breast cancer risk (OR: 1.24, 95 % CI: 1.002–1.54). However, PRS differences between patients and their first- and second-degree relatives showed strong statistical significance. The monogenic variant analysis identified 21 loss-of-function (LOF) variants in the cohort, but only one (BRCA2 9976A > T) was common among breast cancer cases. Our findings highlight the importance of within-family analysis of PRS and the challenges of applying European-derived PRS models to diverse populations.