Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study. Issue 9 (2nd August 2020)

• Record Type: Journal Article
• Authors: Yoshihara, Kosuke; Enomoto, Takayuki; Aoki, Daisuke; Watanabe, Yoh; Kigawa, Junzo; Takeshima, Nobuhiro; Inomata, Hyoe; Hattori, Kana; Jinushi, Masahisa; Tsuda, Hitoshi; Sugiyama, Toru
• Is Part Of: Cancer science. Volume 111:Issue 9(2020)
• Page Start: 3350
• Page End: 3358
• Publication Date: 2020-08-02
• Subjects: BRCA1 gene -- BRCA2 gene -- mutation -- ovarian cancer -- ovarian cancer cluster region; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14513
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Whether germline (g) breast cancer susceptibility gene ( BRCA ) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for g BRCA1, and between 3249‐5681 bp and 6645‐7471 bp for g BRCA2 ) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of g BRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between g BRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by g BRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for g BRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of g BRCA1 mutations were within the OCCR. Of 30 g BRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with g BRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with g BRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and g BRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among g BRCA mutation carriers. Abstract : We investigated the prevalence of the g BRCA1/2 mutations according to the mutation location inside or outside the OCCR in patients with newly diagnosed ovarian cancer who were enrolled in the CHARLOTTE study. Among Japanese ovarian cancer patients, approximately half of the g BRCA1/2 mutations were located within the OCCR.