Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
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DOI：
10.1001/jama.2018.6228
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发表时间：
2018-06-19
期刊：
影响因子：
--
通讯作者：
Couch FJ
中科院分区：
文献类型：
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作者：
Hu C;Hart SN;Polley EC;Gnanaolivu R;Shimelis H;Lee KY;Lilyquist J;Na J;Moore R;Antwi SO;Bamlet WR;Chaffee KG;DiCarlo J;Wu Z;Samara R;Kasi PM;McWilliams RR;Petersen GM;Couch FJ
有胰腺癌遗传易感性的个体可能从早期检测中受益。胰腺癌易感基因和与这些基因突变相关的胰腺癌风险尚未明确。确定癌症易感基因的遗传性生殖系突变是否与胰腺癌风险增加相关。病例对照分析，以确定胰腺癌易感基因;纵向分析胰腺癌患者的预后。该研究包括3030名被诊断患有胰腺癌的成年人，并在2000年10月12日至2016年3月31日期间参加了马约诊所登记，最后一次随访于2017年6月22日。参考对照是在公共基因组聚集数据库中具有外显子组序列数据的123136个个体和在外显子组聚集联盟数据库中具有外显子组序列数据的53105个个体。个体根据携带癌症易感基因的有害突变和具有癌症的个人或家族史进行分类。21个癌症易感基因编码区的种系突变通过对基于定制多重聚合酶链反应的面板的产物进行测序来鉴定;通过比较胰腺癌患者与参考对照的基因突变频率来评估基因与胰腺癌的关联。3030例胰腺癌患者的比较（43.2%女性; 95.6%非西班牙裔白色;平均诊断年龄，65.3 [SD，10.7]岁）与参考对照相比，胰腺癌与CDKN 2A突变之间观察到显著相关性。（0.3%的病例和0.02%的对照;比值比[OR]，12.33; 95% CI，5.43-25.61）; TP 53（0.2%的病例和0.02%的对照; OR，6.70; 95% CI，2.52-14.95）; MLH 1（0.13%的病例和0.02%的对照; OR，6.66; 95% CI，1.94-17.53）; BRCA 2（病例组1.9%，对照组0.3%; OR，6.20; 95%CI，4.62-8.17）; ATM（2.3%的病例和0.37%的对照; OR，5.71; 95%CI，4.38-7.33）;和BRCA 1（0.6%的病例和0.2%的对照; OR，2.58; 95%CI，1.54-4.05）。在本病例对照研究中，6个与胰腺癌相关的基因突变在所有10例胰腺癌患者中的发生率为5.5%，其中有胰腺癌家族史的患者为7.9%，无胰腺癌家族史的患者为5.2%。需要进一步研究在其他人群中的复制。
Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined. To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer. Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database. Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer. Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction–based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls. Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43–25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52–14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94–17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62–8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38–7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54–4.05). In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all0 pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.
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DOI：
10.1186/bcr2919
发表时间：
2011-07-25
期刊：
Breast cancer research : BCR
影响因子：
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DOI：
10.1093/bioinformatics/btu137
发表时间：
2014-07-01
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Bioinformatics (Oxford, England)
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DOI：
10.1093/jnci/djw302
发表时间：
2017-07-01
期刊：
Journal of the National Cancer Institute
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DOI：
10.1038/gim.2017.85
发表时间：
2018-01
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
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DOI：
10.1158/1055-9965.epi-15-0455
发表时间：
2016-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
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作者：
Hu C;Hart SN;Bamlet WR;Moore RM;Nandakumar K;Eckloff BW;Lee YK;Petersen GM;McWilliams RR;Couch FJ
通讯作者：
Couch FJ