{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:03:44Z","timestamp":1789783424991,"version":"4.0.1"},"reference-count":29,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RAD51D<\/jats:italic>\n                      has been reported as a breast cancer (BC) and ovarian cancer (OC) predisposition gene, particularly among Caucasian populations. We studied the prevalence of\n                      <jats:italic>RAD51D<\/jats:italic>\n                      variants in Pakistani BC\/OC patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In total, 371 young or familial BC\/OC patients were thoroughly analyzed for\n                      <jats:italic>RAD51D<\/jats:italic>\n                      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\n                      <jats:italic>RAD51D<\/jats:italic>\n                      variants were investigated in 400 unaffected controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No pathogenic\n                      <jats:italic>RAD51D<\/jats:italic>\n                      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\u2019s 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\u2019s daughter had Hodgkin\u2019s 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      No pathogenic\n                      <jats:italic>RAD51D<\/jats:italic>\n                      variant was identified in the current study. Our study data suggested a negligible association of\n                      <jats:italic>RAD51D<\/jats:italic>\n                      variants with BC\/OC risk in Pakistani women.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.37029\/jcas.v10i2.617","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T19:37:21Z","timestamp":1723837041000},"page":"1-10","source":"Crossref","is-referenced-by-count":1,"title":["Marginal Contribution of Pathogenic\n                    <i>RAD51D<\/i>\n                    Germline Variants to Pakistani Early-Onset and Familial Breast\/Ovarian Cancer Patients"],"prefix":"10.2478","volume":"10","author":[{"given":"Noor","family":"Muhammad","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Sohail","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Management and Technology , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hamann","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Breast Cancer, German Cancer Research Center , Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Usman","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"2026091901455543279_j_jcas.v10i2.617_ref_001","doi-asserted-by":"crossref","unstructured":"Yamamoto H, Hirasawa A. Homologous recombination deficiencies and hereditary tumors. Int J Mol Sci 2021;23:348.","DOI":"10.3390\/ijms23010348"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_002","doi-asserted-by":"crossref","unstructured":"Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 2011;43:879-82.","DOI":"10.1038\/ng.893"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_003","doi-asserted-by":"crossref","unstructured":"Suszynska M, Ratajska M, Kozlowski P. BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: Mutation prevalence and precise risk estimates based on a pooled analysis of~ 30,000 cases. J Ovarian Res 2020;13:50.","DOI":"10.1186\/s13048-020-00654-3"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_004","doi-asserted-by":"crossref","unstructured":"Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med 2021;384:440-51.","DOI":"10.1056\/NEJMoa2005936"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_005","doi-asserted-by":"crossref","unstructured":"Yang X, Song H, Leslie G, Engel C, Hahnen E, Auber B, et al. Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D. J Natl Cancer Inst 2020;112:1242-50.","DOI":"10.1093\/jnci\/djaa030"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_006","doi-asserted-by":"crossref","unstructured":"Rashid MU, Muhammad N, Khan FA, Shehzad U, Naeemi H, Malkani N, et al. Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients. Hered Cancer Clin Pract 2020;18:25.","DOI":"10.1186\/s13053-020-00159-6"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_007","doi-asserted-by":"crossref","unstructured":"Rashid MU, Khan FA, Muhammad N, Loya A, Hamann U. 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Recurrent moderate\u2010risk mutations in Finnish breast and ovarian cancer patients. Int J Cancer 2019;145:2692-700.","DOI":"10.1002\/ijc.32309"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_018","doi-asserted-by":"crossref","unstructured":"Cast\u00e9ra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, et al. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet 2014;22:1305-13.","DOI":"10.1038\/ejhg.2014.16"},{"key":"2026091901455543279_j_jcas.v10i2.617_ref_019","doi-asserted-by":"crossref","unstructured":"Singh J, Thota N, Singh S, Padhi S, Mohan P, Deshwal S, et al. Screening of over 1000 Indian patients with breast and\/or ovarian cancer with a multi-gene panel: Prevalence of BRCA1\/2 and non-BRCA mutations. 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