bims-lifras 2023-12-31 papers

Issue of 2023–12–31
two papers selected by
Joanna Zawacka, Karolinska Institutet

Cold Spring Harb Perspect Med. 2023 Dec 27. pii: a041318. [Epub ahead of print]

Germline Genetic Testing for Hereditary Breast and Ovarian Cancer: Current Concepts in Risk Evaluation.

Siddhartha Yadav, Fergus J Couch, Susan M Domchek.

Our understanding of hereditary breast and ovarian cancer has significantly improved over the past two decades. In addition to BRCA1/2, pathogenic variants in several other DNA-repair genes have been shown to increase the risks of breast and ovarian cancer. The magnitude of cancer risk is impacted not only by the gene involved, but also by family history of cancer, polygenic risk scores, and, in certain genes, pathogenic variant type or location. While estimates of breast and ovarian cancer risk associated with pathogenic variants are available, these are predominantly based on studies of high-risk populations with young age at diagnosis of cancer, multiple primary cancers, or family history of cancer. More recently, breast cancer risk for germline pathogenic variant carriers has been estimated from population-based studies. Here, we provide a review of the field of germline genetic testing and risk evaluation for hereditary breast and ovarian cancers in high-risk and population-based settings.

DOI: https://doi.org/10.1101/cshperspect.a041318

Clin Transl Gastroenterol. 2023 Dec 27.

Surveillance Outcome and Genetic Findings in Individuals at High-Risk for Pancreatic Cancer.

Guy Rosner, Erez Scapa, Tomer Ziv, Nathan Gluck, Merav Ben-Yehoyada.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRI) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC-susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs.
METHODS: 239 HRIs from 202 families were tested genetically and underwent prospective pancreatic surveillance for 6 years.
RESULTS: The cohort was divided into 3 groups: familial pancreatic cancer (FPC; 70 individuals, 54 families), familial non-FPC (81 individuals, 73 families), and hereditary pancreatic cancer (PC) (88 individuals, 75 families). PGVs were detected in 37.6% of all families including 11.1% of FPC families and 9.6% of familial non-FPC families. Hereditary PC group had earlier onset of PDAC compared with the other 2 groups. BRCA2 PGV carriers showed earlier onset of PDAC and pancreatic cysts. Of the 239 HRIs, PDAC was detected in 11 individuals (4.6%), with 73% diagnosed at an early stage; 4 (1.67%) had pancreatic neuroendocrine tumor; 6 (2.5%) had main-duct intraductal papillary neoplasm (IPMN); and 41 (17.15%) had side-branch IPMN. 17 individuals were referred to surgery and twelve were alive at end of study.
CONCLUSIONS: The percentage of PDAC was similar in the 3 groups studied. The hereditary PC group, and particularly BRCA2 PGV carriers, had an earlier age of PDAC onset. PGVs were detected in a significant percentage of PC HRIs. Surveillance appears effective for detection of early-stage PDAC and precursor lesions.

DOI: https://doi.org/10.14309/ctg.0000000000000668