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      Clinical analysis and prognosis of synchronous and metachronous multiple primary malignant tumors

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          Abstract

          The aim of this study was to determine the clinical features, treatment factors, and prognosis of patients with multiple primary malignant tumors (MPMTs). In total, 161 patients with MPMTs at our hospital (The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China) were analyzed in this study. We found that among 161 patients with MPMTs, 78 (48.4%) patients had synchronous tumors and 83 (51.6%) patients had metachronous tumors. Most clinical and pathological features were similar in both groups. Most patients with MPMTs were men and older patients (>50 years old), and adenocarcinoma was the most frequent pathology type. The most frequent location of all MPMTs was the digestive system. The leading tumor association was between digestive–digestive tumors, also. However, patients with synchronous tumors and MPMTs of the digestive system showed a shorter survival time. In the metachronous cancer group, the median interval time was 60 months, and a short interval time (≤60 months) was associated with a shorter survival time. In addition, survival time was increased in the younger age group (≤50 years old) and in patients who accepted surgery-based comprehensive therapy. However, only interval time (≤60 months) was an independent prognostic factor associated with survival for the metachronous cancer group. Therefore, careful surveillance and follow-up are especially important in these patients.

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          Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas

          Many individuals with multiple or large colorectal adenomas, or early-onset colorectal cancer (CRC), have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline variants in several multiple adenoma and/or CRC cases, but in no controls. The susceptibility variants appear to have high penetrance. POLD1 is also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proof-reading (exonuclease) domain of DNA polymerases ε and δ, and are predicted to impair correction of mispaired bases inserted during DNA replication. In agreement with this prediction, mutation carriers’ tumours were microsatellite-stable, but tended to acquire base substitution mutations, as confirmed by yeast functional assays. Further analysis of published data showed that the recently-described group of hypermutant, microsatellite-stable CRCs is likely to be caused by somatic POLE exonuclease domain mutations.
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            Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program.

            An overview of cancer statistics and trends for selected cancers and all sites combined are given based on data from the Surveillance, Epidemiology, and End Results Program. Median age at diagnosis for all sites combined shows a 2-year increase from 1974 through 1978 to 1999 through 2003. Changes in cancer incidence rates from 1975 through 2003 are summarized by annual percent change for time periods determined by joinpoint regression analysis. After initial stability (1975-1979), incidence rates in women for all cancer sites combined increased from 1979 through 2003, although the rate of increase has recently slowed. For men, initial increases in all cancer sites combined (1975-1992) are followed by decreasing incidence rates (1992-1995) and stable trends from 1995 through 2003. Female thyroid cancer shows continued increasing incidence rates from 1981 through 2003. Blacks have the highest incidence and mortality rates for men and women for all cancer sites combined. Based on 2001 through 2003 data, the likelihood of developing cancer during one's lifetime is approximately one in two for men and one in three for women. Five-year relative survival for all stages combined (1996-2002) ranges from 16% for lung to 100% for prostate cancer patients. Cancer survival varies by stage of disease and race, with lower survival in blacks compared with whites. The risk of developing subsequent multiple primary cancers varies from 1% for an initial liver primary diagnosis to 16% for initial bladder cancer primaries. The impact on the future U.S. cancer burden is estimated based on the growing and aging U.S. population. The number of new cancer patients is expected to more than double from 1.36 million in 2000 to almost 3.0 million in 2050.
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              Multiple primary malignant neoplasms: case report and a comprehensive review of the literature.

              A case is presented of an elderly patient with synchronous ureteral/bladder/urethral transitional cell carcinoma and prostatic adenocarcinoma. In a subsequent review of 1,104,269 cancer patients in the literature, the reported prevalence of multiple primary malignant neoplasms (MPMN) varies between 0.734% and 11.7%. It appears that MPMN might occur more frequently than can be explained on the basis of random chance. As expected, the incidence of developing MPMN is noted to rise with increasing age. In addition, the preponderance of men with MPMN is caused primarily by the high frequency of prostatic cancer. Current studies and research need to address the potential of older cancer patients being at higher risk of second primaries.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                April 2017
                28 April 2017
                : 96
                : 17
                : e6799
                Affiliations
                [a ]Department of Oncology, The First Affiliated Hospital of Xian Jiaotong University, Xi’an
                [b ]Department of Medical Oncology, Xianyang Center Hospital, Xianyang, Shaanxi, PR China.
                Author notes
                []Correspondence: Prof Jin Yang, Department of Oncology, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, Shaanxi 710061, PR China (e-mail: yangjin@ 123456mail.xjtu.edu.cn )
                Article
                MD-D-16-07265 06799
                10.1097/MD.0000000000006799
                5413286
                28445321
                08d9ab2c-3a62-4dbd-b8b0-c798377bb1aa
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 4 December 2016
                : 5 April 2017
                : 9 April 2017
                Categories
                4400
                Research Article
                Observational Study
                Custom metadata
                TRUE

                clinical characteristics,metachronous,multiple primary malignant tumors,prognosis,synchronous

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