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PubMed · 42118082

Germline ATRIP variants and the risk of ovarian cancer.

Neda Zamani·Dominika Wokołorczyk·Wojciech Kluźniak·Alicja Ogrodniczak·Anna Jakubowska·Mehar Chahal·Klaudia Stempa·Katarzyna Gliniewicz·Tomasz Huzarski·Helena Rudnicka·Marek Szwiec·Malgorzata Stawicka·Ewa Kaznowska·Tomasz Kluz·Paweł Domagała·Tadeusz Dębniak·John McLaughlin·Jan Lubiński·Jacek Gronwald·Steven A Narod·Joanne Kotsopoulos·Cezary Cybulski·Mohammad R Akbari
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Abstract

PURPOSE: We have previously reported that inherited variants in ATRIP confer a 3-fold risk of developing breast cancer. Here, we investigated potential association between this novel breast cancer susceptibility gene and the risk of ovarian cancer. METHODS: We genotyped the ATRIP c.1152_1155del p.(Gly385Ter) Polish founder variant on germline DNA from 3404 Polish women with ovarian cancer and 9285 healthy controls. Additionally, we sequenced all coding exons of ATRIP among 1322 unselected ovarian cancer patients and 930 cancer-free women from Ontario, Canada. RESULTS: The heterozygous ATRIP c.1152_1155del p.(Gly385Ter) variant was identified in 8 of 3404 ovarian cancer cases and 11 of 9285 controls in the Polish population (OR = 1.98, 95% CI = 0.79-4.94, P = .19). In the Ontario cohort, 4 ovarian cancer cases harbored ATRIP loss-of-function (LoF) variants, versus none observed among controls (OR = 5.6, P = .14). In a combined analysis of both cohorts, adjusted for age, self-reported ethnicity, and study, ATRIP LoF variants were significantly associated with ovarian cancer risk (OR = 2.51, 95% CI = 1.108-5.699, P = .037). CONCLUSION: ATRIP plays a critical role in DNA damage response and genomic stability. Our findings support its candidacy as a novel ovarian cancer susceptibility gene.

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HumansFemaleOvarian NeoplasmsGerm-Line MutationGenetic Predisposition to DiseaseMiddle AgedDNA-Binding ProteinsAdultCase-Control StudiesAgedRisk FactorsPolandGenotypeOntarioATRIPCancer susceptibilityDNA damage responseGermline variantsOvarian cancerJournal ArticleResearch Support, Non-U.S. Gov't

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Neda Zamani, Dominika Wokołorczyk, Wojciech Kluźniak, Alicja Ogrodniczak, Anna Jakubowska, Mehar Chahal, Klaudia Stempa, Katarzyna Gliniewicz, Tomasz Huzarski, Helena Rudnicka, Marek Szwiec, Malgorzata Stawicka, Ewa Kaznowska, Tomasz Kluz, Paweł Domagała, Tadeusz Dębniak, John McLaughlin, Jan Lubiński, Jacek Gronwald, Steven A Narod, Joanne Kotsopoulos, Cezary Cybulski, Mohammad R Akbari. 2026-05-12. Germline ATRIP variants and the risk of ovarian cancer.. https://doi.org/10.1016/j.gim.2026.102547

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