Marginal Contribution of Pathogenic Germline Variants to Pakistani Early-Onset and Familial Breast/Ovarian Cancer Patients

Overview

Journal J Cancer Allied Spec

Specialty Oncology

Date 2024 Aug 19

PMID 39156943

Authors

Noor Muhammad

Muhammad Sohail Afzal

Ute Hamann

Muhammad Usman Rashid

Affiliations

Soon will be listed here.

Abstract

Introduction: has been reported as a breast cancer (BC) and ovarian cancer (OC) predisposition gene, particularly among Caucasian populations. We studied the prevalence of variants in Pakistani BC/OC patients.

Materials And Methods: In total, 371 young or familial BC/OC patients were thoroughly analyzed for sequence variants using denaturing high-performance liquid chromatography pursued by DNA sequencing of differentially eluted amplicons. We also assessed the pathogenic effects of novel variants using in-silico algorithms. All detected variants were investigated in 400 unaffected controls.

Results: No pathogenic variant was detected. However, we identified nine unique heterozygous variants. Of these, two missense variants (p.Pro10Leu and p.Ile311Asn) and one intronic variant (c.481-26_23delGTTC) were classified as in silico-predicted variants of uncertain significance, with a frequency of 0.8% (3/371). The p.Pro10Leu variant was detected in a 28-year-old female BC patient of Punjabi ethnic background, whose mother and maternal cousin had BCs at ages 53 and 40, respectively. This variant was also detected in 1/400 (0.25%) healthy controls, where the control subject's daughter had acute lymphoblastic leukemia. The p.Ile311Asn variant was identified in a female BC patient at age 29 of Punjabi ethnicity and in 1/400 (0.25%) healthy controls, where the control subject's daughter had Hodgkin's disease at age 14. A novel intronic variant, c.481-26_-23delGTTC, was found in a 30-year-old Punjabi female BC patient but not in 400 healthy controls.

Conclusion: No pathogenic variant was identified in the current study. Our study data suggested a negligible association of variants with BC/OC risk in Pakistani women.

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