Germline mutations in Japanese familial pancreatic cancer patients

Erina Takai, Shinichi Yachida, Kyoko Shimizu, Junji Furuse, Emi Kubo, Akihiro Ohmoto, Masami Suzuki, Ralph H Hruban, Takuji Okusaka, Chigusa Morizane, Toru Furukawa

Research output: Contribution to journalArticle

Abstract

Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC).We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC. There were no significant differences between the FPC cases and sporadic cases in terms of gender, age, tumor location, stage, family history of any cancer except PDAC, and personal history of smoking, other cancers, diabetes mellitus and chronic pancreatitis. In the FPC patients, we then investigated the prevalence of germline mutations in 21 genes associated with hereditary predispositions for pancreatic, breast and ovarian cancers by means of the next-generation sequencing using a custom multiple-gene panel. We found that eight (14.5%) of the 54 FPC patients with available germline DNA carried deleterious mutations in BRCA2, PALB2, ATM, or MLH1. These results indicate that a significant fraction of patients with PDAC in Japan have a family history of pancreatic cancer, and some of them harbor deleterious causative mutations in known FPC predisposition genes.

Original languageEnglish (US)
Pages (from-to)74227-74235
Number of pages9
JournalOncotarget
Volume7
Issue number45
DOIs
StatePublished - 2016

Fingerprint

Germ-Line Mutation
Pancreatic Neoplasms
Adenocarcinoma
Neoplasm Genes
Mutation
Chronic Pancreatitis
Ovarian Neoplasms
Genes
Neoplasms
Diabetes Mellitus
Japan
Smoking
Breast Neoplasms

Keywords

  • ATM
  • BRCA2
  • Familial predisposition
  • PALB2
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Takai, E., Yachida, S., Shimizu, K., Furuse, J., Kubo, E., Ohmoto, A., ... Furukawa, T. (2016). Germline mutations in Japanese familial pancreatic cancer patients. Oncotarget, 7(45), 74227-74235. https://doi.org/10.18632/oncotarget.12490

Germline mutations in Japanese familial pancreatic cancer patients. / Takai, Erina; Yachida, Shinichi; Shimizu, Kyoko; Furuse, Junji; Kubo, Emi; Ohmoto, Akihiro; Suzuki, Masami; Hruban, Ralph H; Okusaka, Takuji; Morizane, Chigusa; Furukawa, Toru.

In: Oncotarget, Vol. 7, No. 45, 2016, p. 74227-74235.

Research output: Contribution to journalArticle

Takai, E, Yachida, S, Shimizu, K, Furuse, J, Kubo, E, Ohmoto, A, Suzuki, M, Hruban, RH, Okusaka, T, Morizane, C & Furukawa, T 2016, 'Germline mutations in Japanese familial pancreatic cancer patients', Oncotarget, vol. 7, no. 45, pp. 74227-74235. https://doi.org/10.18632/oncotarget.12490
Takai E, Yachida S, Shimizu K, Furuse J, Kubo E, Ohmoto A et al. Germline mutations in Japanese familial pancreatic cancer patients. Oncotarget. 2016;7(45):74227-74235. https://doi.org/10.18632/oncotarget.12490
Takai, Erina ; Yachida, Shinichi ; Shimizu, Kyoko ; Furuse, Junji ; Kubo, Emi ; Ohmoto, Akihiro ; Suzuki, Masami ; Hruban, Ralph H ; Okusaka, Takuji ; Morizane, Chigusa ; Furukawa, Toru. / Germline mutations in Japanese familial pancreatic cancer patients. In: Oncotarget. 2016 ; Vol. 7, No. 45. pp. 74227-74235.
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