Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study

Kosuke Yoshihara, Takayuki Enomoto, Daisuke Aoki, Yoh Watanabe, Junzo Kigawa, Nobuhiro Takeshima, Hyoe Inomata, Kana Hattori, Masahisa Jinushi, Hitoshi Tsuda, Toru Sugiyama

Research output: Contribution to journalArticle

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 gBRCA1, and between 3249-5681 bp and 6645-7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 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 gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 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 gBRCA mutation carriers.

Original languageEnglish
JournalCancer science
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • BRCA1 gene
  • BRCA2 gene
  • mutation
  • ovarian cancer
  • ovarian cancer cluster region

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yoshihara, K., Enomoto, T., Aoki, D., Watanabe, Y., Kigawa, J., Takeshima, N., Inomata, H., Hattori, K., Jinushi, M., Tsuda, H., & Sugiyama, T. (Accepted/In press). Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study. Cancer science. https://doi.org/10.1111/cas.14513