Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report

Abe, Kodai; Ueki, Arisa; Urakawa, Yusaku; Kitago, Minoru; Yoshihama, Tomoko; Nanki, Yoshiko; Kitagawa, Yuko; Aoki, Daisuke; Kosaki, Kenjiro; Hirasawa, Akira

doi:10.1186/s13053-020-00160-z

Cited by 6 publications

(8 citation statements)

References 19 publications

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“…A family history of cancer was an independent risk factor for both pancreatic cancer and high-risk sIPMN (Table 4 and Supplemental Table 1, http://links.lww.com/MPA/A962). This suggested the involvement of genetic factors in IPMN and pancreatic cancer 24 . Intraductal papillary mucinous neoplasm can become a prognostic factor for hereditary cancer syndromes, as shown in Supplemental Table 5 http://links.lww.com/MPA/A962 25–27 .…”

Section: Discussionmentioning

confidence: 97%

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Fukushima

Abe²,

Kitago³

et al. 2022

Pancreas

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Objectives: Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. Methods:We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN.Results: Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-tolymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (

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Section: Discussionmentioning

confidence: 97%

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Fukushima

Abe²,

Kitago³

et al. 2022

Pancreas

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“…One patient (#7) underwent commercial testing for multiple cancer genes, and a heterozygous PALB2 pathogenic variant (c.1675_1676inv [p. Gln559*]) and a heterozygous NBN pathogenic variant (c.265C>T [p. Arg89*]) were identified that has been reported elsewhere. 20 …”

Section: Resultsmentioning

confidence: 99%

Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross‐sectional study

et al. 2022

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Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole‐exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first‐degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

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“…NBN pathogenic variants are mostly reported in breast cancer, but recent reports link them to pancreatic cancer as well. However, the cumulative incidence or RR has not been reported [16,21].…”

Section: Nbnmentioning

confidence: 99%

“…PALB2 (partner and localizer of BRCA2) is also involved in DNA damage repair and Fanconi anemia, which is strongly associated with breast, ovarian, and pancreatic cancer [15,16]. PALB2 pathogenic germline variants are associated with a 7.18, 2.91, and 2.37 RR of developing female breast, ovarian, and pancreatic cancer, respectively, and their estimated incidence up to age 80 years is 53%, 5%, and 2%-3%, respectively [17].…”

Section: Palb2mentioning

confidence: 99%

Hereditary pancreatic cancer

et al. 2021

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Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

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Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report

Cited by 6 publications

References 19 publications

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross‐sectional study

Hereditary pancreatic cancer

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