Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome

Abstract

Background Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in the CDH1 gene. Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information about CDH1 variant status, HDGC risk, and limit familial transmission of CDH1 variants. To date, however, little is known about the attitudes of individuals with CDH1 variants towards PGT. Methods Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants with CDH1 variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life. Results Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals with CDH1 variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants’ quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications. Conclusion PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyond CDH1 carriers to family members’ reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals with CDH1 variants.

Public Awareness and Acceptability of PGT-M in Cancer Predisposition Syndromes

“…In Shah al. 's study targeting patients with CDH1 variants, 40% of respondents stated they wou consider PGT, 35% would not and 25% were uncertain; 90.5% of patients thought th physicians should discuss PGT with individuals carrying CDH1 variants [47].…”

“…In Shah et al's study, of the two CHD1 carriers who wanted to have a biological child, one was "very likely" to use PGT, whereas the other one was "very unlikely". Among respondents who already had children, a small majority indicated that they would have considered using PGT if it had been available [47].…”

“…Similar considerations emerged from a cross-sectional study by Shah et al targeting patients with a genetic predisposition to develop gastric tumors. Out of 38 investigated patients, 13 identified their "philosophy of life" as an influencing factor, followed by "God, religion, and morality" (10/38), the "desire to eradicate the variant for future generations" (9/38), and the desire to "minimize anxiety or suffering," both on a personal level and for their offspring (5/38) [47].…”

“…Comparison between the percentage of patients who think that PGT should be offered as a reproductive option for couples affected by CPSs (yellow) vs. percentage of patients who would consider PGT for themselves (orange)[1,41,46,47].…”