Return of Individual Genomic Results to Germline Pathogenic Variant Carriers of Hereditary Cancer in Population Based Cohort Study

Return of individual genomic results(ROGR)to participants in population-based biobank has been rarely conducted in research settings, and the procedure of ROGR performed in foreign countries may not be simply applied to Japanese participants, because of the difference in social background. The Tohoku Medical Megabank Project, which was launched in 2012 aiming to build a foundation of personalized genomic medicine, obtained the consent from research participants by explaining the future possibility of ROGR. After careful consideration of appropriate procedure for ROGR, individual genomic results were returned to 111 pathogenic variant(PV)carriers of hereditary breast and ovarian cancer syndrome(HBOC)or Lynch syndrome(LS)based on 50,000 whole genome sequencing(WGS)data in FY 2022. Since majority of the participants has no cancer diagnosis, participants' right to not know was carefully considered. In addition, the variants to be returned were carefully evaluated by using multiple databases, and the WGS results of the participants were further confirmed by the single- site analysis. When the genomic results were returned, the participants were informed about clinical risk surveillance at the hospital. Seventy-eight and 33 PV carriers of HBOC and LS, respectively, participated in the study. Most participants were in their 30s or 40s. Unexpectedly, validation testing results of 12 LS participants were found to be negative or variant of uncertain significance, because detecting these variants by WGS were technically challenging. Twenty-eight participants (HBOC 20, LS 8)had been diagnosed as cancer, and 6 females who had breast cancer were genetically diagnosed as HBOC and underwent or planned risk-reducing surgery. Eighteen participants refused to undergo clinical risk surveillance because of the medical expense that is not covered by health insurance and the burden of visiting the hospital. The opportunity to undergo medical surveillance should be provided to population-based cohort participants who carry actionable pathogenic variants, and ROGR to general population should be promoted to create the base of personalized genomic medicine.

Medienart:	Artikel

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	Zur Gesamtaufnahme - volume:51
Enthalten in:	Gan to kagaku ryoho. Cancer & chemotherapy - 51(2024), 3 vom: 23. März, Seite 231-236

Sprache:	Japanisch

Beteiligte Personen:	Ohneda, Kinuko [VerfasserIn]

Themen:	English Abstract Journal Article

Anmerkungen:	Date Completed 19.03.2024 Date Revised 19.03.2024 published: Print Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM36984484X