• Title, Summary, Keyword: Familial cancer

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The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome

  • Lener, Marcin R.;Kashyap, Aniruddh;Kluzniak, Wojciech;Cybulski, Cezary;Soluch, Agnieszka;Pietrzak, Sandra;Huzarski, Tomasz;Gronwald, Jacek;Lubinski, Jan
    • Cancer Research and Treatment
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    • v.49 no.2
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    • pp.430-436
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    • 2017
  • Purpose Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland. Materials and Methods In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes. Results A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026). Conclusion The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome.

Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations

  • Zhu, Xinyi;Tian, Tian;Ruan, Miao;Rao, Jia;Yang, Wentao;Cai, Xu;Sun, Menghong;Qin, Guangqi;Zhao, Zhonghua;Wu, Jiong;Shao, Zhimin;Shui, Ruohong;Hu, Zhen
    • Journal of Breast Cancer
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    • v.21 no.3
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    • pp.297-305
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    • 2018
  • Purpose: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. Methods: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. Results: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. Conclusion: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.

Estimating the Genetic Epidemiology Parameters of Selected Cancers in Korea Population - The Korean Twin Study -

  • Sung, Jooh-On
    • Genomics & Informatics
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    • v.3 no.4
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    • pp.159-165
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    • 2005
  • The Korean Twin Register (n=154,783 pairs) was reported in 2002 as the first nationwide twin study in Korea and the largest study in Asia. The Twin Register has the information of disease outcomes since 1990, and basic clinical and questionnaire data from biennial health examination provided by Korea National Health Service. The author attempted to calculate some of the genetic parameters of cancers in this population. Common cancers in Korea known to have familial aggregation (colon and breast) and cancers of which familial aggregation is unclear (stomach cancer) were examined for their familial recurrence risks. There were 699 stomach cancers, 438 breast and 491 colorectal cancers cases in the twin register between 1991 and 2003. Like-sex twins showed recurrence risks (${\lambda}_{LS}$) of 5.1 (95% CI 3.7-6.9) for stomach cancers, 15.5 (95% CI1 0.9-20.2) for female breast cancers, and 28.1 (95% CI 23.5-34.4) for colon cancers. Colorectal cancers of female like-sex twins show significantly higher familial recurrence risk 40.7 (95% CI 34.6-47.4), suggesting higher genetic contribution in women than in men. The results show increased familial risks compared with previous studies from the same register and are largely compatible with other studies. The data of the Twin Register could be used for estimating population level genetic parameters, as well as base of the various studies.

Familial Breast Cancer Registry Program in Patients Referred to the Cancer Institute of Iran

  • Sabokbar, Tayebeh;Khajeh, Elias;Taghdiri, Foad;Peyghambari, Vahideh;Shirkoohi, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2675-2679
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    • 2012
  • Introduction: Annually a considerable number of people die because of breast cancer, a common disease among women also in Iran. Identifying risk factors and susceptible people can lead to prevention or at least early diagnosis. Among susceptibility risks, 5-10% of patients have a family history predisposing factor which can influence the risk of incidence among the family. Having a registry program can be a more practical way to screen high risk families for preventive planning. Method: Based on inclusion criteria, a questionnaire was prepared and after a pilot study on a small number of patients, actual data were collected on 400 patients and processed in SPSS 16.0. Results: Totally, 28.2%of the patients were younger than 40 years old and 36.8% had the included criteria for familial breast cancer (FBC). 102 patient's samples could be compared for receptor presentation. Similar to other studies, the number of triple negative breast cancers increased as the age decreased. Conclusion: The high percentage of patients with FBC among 400 cases in this study demonstrates that in order to design an infrastructural diagnostic protocol and screening of patients with FBC, a precise survey related to frequency and founder mutations of FBC is needed nationwide.

Colon Cancer Prevention by Detection of APC Gene Mutation in a Family with Attenuated Familial Adenomatous Polyposis

  • Poovorawan, Kittiyod;Suksawatamnuay, Sirinporn;Sahakitrungruang, Chucheep;Treeprasertsuk, Sombat;Wisedopas, Naruemon;Komolmit, Piyawat;Poovorawan, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5101-5104
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    • 2012
  • Background: Genetic mutation is a significant factor in colon CA pathogenesis. Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease characterized by multiple colorectal adenomatous polyps affecting a number of cases in the family. This report focuses on a family with attenuated familial adenomatous polyposis (AFAP) with exon 4 mutation, c.481C>T p.Q161X of the APC gene. Methods: We analyzed 20 members of a family with AFAP. Clinical and endoscopic data were collected for phenotype determination. Genetic analysis was also performed by direct sequencing of the APC gene. Result: Five patients with a phenotype of AFAP were found. Endoscopic polyposis was demonstrated among the second generation with genotype mutation of the disease (age > 50 years) consistent with delayed phenotypic adenomatous polyposis in AFAP. APC gene mutation was identified in exon 4 of the APC gene, with mutation points of c.481C>T p.Q161X. Laparoscopic subtotal colectomy was performed to prevent carcinogenesis. Conclusion: A family with attenuated familial adenomatous polyposis of APC related to exon 4 mutation, c.481C>T p.Q161X, was reported and the phenotypic finding was confirmed by endoscopic examination. Genetic mutation analysis might be advantageous in AFAP for long term colon cancer prevention and management due to subtle or asymptomatic phenotype presentation in early adulthood.

A Registry Program for Familial Gastric Cancer Patients Referred to Cancer Institute of Iran

  • Etemadi, Mehrnoosh;Pourian, Mandana;Shakib, Asyeh;Sabokbar, Tayebeh;Peyghanbari, Vahideh;Shirkoohi, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2141-2144
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    • 2014
  • Background: Gastric cancer is the second most common cause of cancer death. It has a poor prognosis with only 5-10% of hereditary etiology. If it is diagnosed, it could be helpful for screening the other susceptible members of a family for preventive procedures. Usually it is identified by symptoms such as presence of cancer in different members of family, some special type of pathology such as diffused adenocarcinoma, having younger age and multiple cancer syndromes. Hence, designing a registry program can be a more practical way to screen high risk families for a preventive program. Materials and Methods: Based on the inclusion criteria, a questionnaire was prepared. After pilot on a small number of patients, the actual data was collected from 197 patients and processed in SPSS 16.0. Results: Totally, 11.8% of the patients were younger than 45 years old. Blood type 'A' was dominant and males had a higher risk behavior with higher consumption of unhealthy food. Adenocarcinoma was reported in majority of cases. 21.8% of the patients had the including criteria for familial gastric cancer (FGC). Conclusions: The high percentage of FGC population compared to the other studies have revealed a need to design an infrastructural diagnostic protocol and screening program for patients with FGC, plus preventive program for family members at risk which could be done by a precise survey related to frequency and founder mutations of FGC in a national registry program.

Hereditary Colorectal Cancer (유전성 대장암)

  • Kim, Duck-Woo
    • Journal of Genetic Medicine
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    • v.7 no.1
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    • pp.24-36
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    • 2010
  • Colorectal cancer is one of the most steeply increasing malignancies in Korea. Among 398,824 new patients recorded by the Korea Central Cancer Registry between 2003 and 2005, 47,915 cases involved colorectal cancers, accounting for 12.0 % of all malignancies. In 2002, total number of colorectal cancer cases had accounted for 11.2 % of all malignancies. Hereditary syndromes are the source of approximately 5% to 15% of overall colorectal cancer cases. Hereditary colorectal cancers are divided into two types: hereditary nonpolyposis colorectal cancer (HNPCC), and cancers associated with hereditary colorectal polyposis, including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis, and the recently reported hMutYH (MYH)-associated polyposis (MAP). Hereditary colorectal cancers have unique clinical features distinct from sporadic cancer because these are due to germline mutations of the causative genes; (i) early age-of-onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent association with extracolonic manifestations. The management strategy for patients with hereditary colorectal cancer is quite different from that for sporadic cancer. Furthermore, screening, genetic counseling, and surveillance for at-risk familial member are also important. A well-organized registry can plays a central role in the surveillance and management of families affected by hereditary colorectal cancers. Here, we discuss each type of hereditary colorectal cancer, focusing on the clinical and genetic characteristics, management, genetic screening, and surveillance.

Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases

  • Anwar, Sumadi Lukman;Haryono, Samuel J;Aryandono, Teguh;Datasena, I Gusti Bagus
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1987-1991
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    • 2016
  • Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.

Isoperistaltic Jejunal Loop Interposition after Total Gastrectomy for Gastric Cancer in Patients with Familial Adenomatous Polyposis

  • Zuin, Matteo;Celotto, Francesco;Pucciarelli, Salvatore;Urso, Emanuele Damiano Luca
    • Journal of Gastric Cancer
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    • v.20 no.2
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    • pp.225-231
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    • 2020
  • Gastric cancer is a rare condition affecting patients with familial adenomatous polyposis (FAP). The mainstay of treatment is total gastrectomy. Since duodenal cancer is the most common cause of death after total colectomy in FAP, endoscopic surveillance for duodenal cancer is mandatory. Here, we describe the use of an isoperistaltic jejunal loop interposition technique to reconstruct the digestive tract after total gastrectomy in 2 patients with FAP. There were no early or late complications. Both patients are still alive and in good clinical condition. They did not experience weight loss or symptoms of dumping syndrome. Duodenal endoscopic surveillance after this technique was easier than after the classical Roux-en-Y reconstruction. Hence, regular follow-up was possible for both patients.

Evaluation of Endoscopic Characteristics of Upper Gastrointestinal Polyps in Patients with Familial Adenomatous Polyposis

  • Fatemi, Seyed Reza;Safaee, Azadeh;Pasha, Sara;Pourhoseingholi, Mohamad Amin;Bahrainei, Rasool;Molaei, Mahsa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6945-6948
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    • 2014
  • Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients. Materials and Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed. Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia. Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.