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  • Hemminki, Kari, et al. (författare)
  • Genetics of gallbladder cancer
  • 2017
  • Ingår i: The Lancet Oncology. - Elsevier. - 1470-2045. ; 18:6, s. 296-296
  • Tidskriftsartikel (refereegranskat)
  • Hemminki, Kari, et al. (författare)
  • Location of metastases in cancer of unknown primary are not random and signal familial clustering.
  • 2016
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is a fatal disease diagnosed through metastases. It shows intriguing familial clustering with certain defined primary cancers. Here we examine whether metastatic location in CUP patients is related to primary non-CUP cancers in relatives based on the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for CUP patients defined by metastatic location depending on cancer in their first degree relatives. SIRs for CUP were high in association with liver (3.94), ovarian (3.41), lung (2.43) and colorectal cancers (1.83) in relatives. The SIR was 1.63 for CUP with metastases in the abdomen when a relative was diagnosed with ovarian cancer. CUP with liver metastases associated with liver (1.44) cancer in relatives. CUP with head and neck region metastases associated with relatives' esophageal (2.87) cancer. CUP metastases in the thorax associated with a relative's cancers in the upper aerodigestive tract (2.14) and lung (1.74). The findings, matching metastatic location in CUP and primary cancer in relatives, could be reconciled if these cases of CUP constitute a phenotypically modified primary lacking tissue identification, resulting from epitope immunoediting. Alternatively, CUP metastases arise in a genetically favored tissue environment (soil) promoting growth of both primary cancers and metastases (seeds).
  • Hemminki, Kari, et al. (författare)
  • Site-specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries.
  • 2012
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136.
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary site (CUP) is a fatal cancer ranking among the five most common cancer deaths. CUP is diagnosed through metastases, which are limited to lymph nodes in some patients. Cause-specific survival data could guide the search for hidden primary tumors and help with therapeutic choices. The CUP patients were identified from the Swedish Cancer Registry between 1987 and 2008; 1444 patients had only lymph node metastasis of defined histology (adenocarcinoma, squamous cell or undifferentiated). Site-specific cancer deaths were analyzed by lymph node location and histology. Kaplan-Meier survival curves were compared with metastatic primary cancer at related sites. Among the patients with metastasis to head and neck lymph nodes, 117 (59.1% of the specific cancer deaths) died of lung tumors. Patients with axillary lymph node metastasis died of lung and breast tumors in equal proportions (40.2% each). Also, squamous cell CUP in head and neck lymph nodes was mainly associated with lung tumor deaths (53.1%). With a few exceptions, survival of CUP patients with lymph node metastasis was indistinguishable from survival of patients with metastatic primary cancer originating from the organs drained by those nodes. The association between lymph node CUP metastases with cancer deaths in the drained organ and the superimposable survival kinetics suggests that drained organs host hidden primaries. Importantly, half of all site-specific cancer deaths (266/530) were due to lung tumors. Thus, an intense search should be mounted to find lung cancer in CUP patients with lymph node metastases.© 2012 Wiley Periodicals, Inc.
  • Hemminki, Kari, et al. (författare)
  • Site-specific survival rates for cancer of unknown primary (CUP) according to location of metastases.
  • 2013
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 133:1, s. 182-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is diagnosed at the metastatic stage and despite extensive diagnostic work-up the primary tumor often remains unidentified. Limited population-based survival data are available for metastatic location and none are available that link the location with the cause of death, which might give clues about the tissue of origin. A total of 9,306 CUP patients with extranodal metastases of adenocarcinoma and undifferentiated histology were identified from the Swedish Cancer Registry. Hazard ratios (HRs), mean survival times and Kaplan-Meier survival curves were provided according to CUP location at diagnosis and cause of death. The median survival was shortest (2 months) for patients with liver and longest (5 months) for those with nervous system metastases. Lung cancer was the most common cause of death in patients with CUP metastasis in the respiratory system, nervous system, bone and skin, with a median survival of 3 months. Patients with peritoneal/retroperitoneal and pelvical metastasis died of ovarian cancer, with a favorable median survival of 8 months, but also of pancreatic and colorectal cancers. Patients with pancreatic, liver, biliary and colorectal cancers with liver metastasis succumbed quickly. The data show that the location of metastases predicts site-specific cancer deaths which in turn may point to the hidden primary tumor. The results should facilitate the management of CUP in proposing that the diagnostic arsenal should target the lungs when metastases are diagnosed in the respiratory or nervous system, bone or skin; ovarian tumors should be suspected after diagnosis of pelvical metastases. © 2012 Wiley Periodicals, Inc.
  • Hemminki, Kari, et al. (författare)
  • Surveillance Bias in Cancer Risk after Unrelated Medical Conditions : Example Urolithiasis
  • 2017
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We analysed cancer risks in patients with urinary tract stones but some features of the generated results alarmed us about possible surveillance bias, which we describe in this report. We used nationwide Swedish hospital records to identify patients with urinary tract stones (N = 211,718) and cancer registration data for cancer patients for years 1987 to 2012. Standardized incidence ratios (SIRs) for cancer were calculated after the last medical contact for urinary tract stones. All cancers were increased after kidney (SIR 1.54, 95%CI: 1.50-1.58), ureter (1.44, 1.42-1.47), mixed (1.51, 1.44-1.58) and bladder stones (1.63, 1.57-1.70). The risk of kidney cancer was increased most of all cancers after kidney, ureter and mixed stones while bladder cancer was increased most after bladder stones. All SIRs decreased steeply in the course of follow-up time. Tumour sizes were smaller in kidney cancer and in situ colon cancers were more common in patients diagnosed after urinary tract stones compared to all patients. The results suggest that surveillance bias influenced the result which somewhat surprisingly appeared to extend past 10 years of follow-up and include cancers at distant anatomical sites. Surveillance bias may be difficult to avoid in the present type of observational studies in clinical settings.
  • Hemminki, Kari, et al. (författare)
  • Survival in cancer of unknown primary site: population-based analysis by site and histology
  • 2012
  • Ingår i: Annals of Oncology. - Oxford University Press. - 1569-8041. ; 23:7, s. 1854-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is diagnosed at a metastatic stage, conferring an unfavorable prognosis. The natural history of the disease is poorly understood, which complicates diagnosis, treatment and follow-up. Population-based survival data are lacking regarding location and histology of metastases. From the Swedish Cancer Registry, 18 911 CUP patients were identified between years 1987 and 2008. Survival was analyzed by Kaplan-Meier survival curves and Cox regression. Adenocarcinoma accounted for 70% of all extranodal cases with a 12-month survival of 17% and the median survival of 3 months. Adenocarcinoma was also the most common histology (33.4%) when metastases were limited to lymph nodes, with a 12-month survival of 41% and median survival of 8 months. For extranodal metastases, the extremes in survival were small intestinal cancer with poor prognosis and mediastinal cancer with favorable prognosis. For nodal metastases, patients affected in the head and neck, axillary and inguinal regions had the best prognosis and those with abdominal and intrapelvic metastases the worst prognosis. The present data underline the importance of histology and location of metastasis in assisting clinical decision making: hazard ratios differed by a factor of five among extranodal and nodal metastases.
  • Hemminki, Kari, et al. (författare)
  • The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution.
  • 2010
  • Ingår i: Journal of Autoimmunity. - Elsevier. - 0896-8411. ; 34, s. 307-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous family and twin studies have indicated that Graves' disease has a heritable component. Family studies have also shown that some autoimmune disease cluster in families and genetic studies have been able to show shared susceptibility genes. In the present nation-wide study we describe familial risk for Graves' disease among parents and offspring, singleton siblings, twins and spouses with regard to age of onset, gender and number and type of affected family members. Additionally familial association of Graves' disease with any of 33 other autoimmune and related conditions was analyzed. The Swedish Multigeneration Register on 0-75-year-old subjects was linked to the Hospital Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for Graves' disease compared to those whose relatives were unaffected. The total number of hospitalized Graves' patients was 15,743. Offspring with an affected family member constituted 3.6% of all patients among offspring. The familial SIR was 5.04 for individuals whose sibling was affected but it increased to 310 when two or more siblings were affected; the SIR in twins was 16.45. Familial risks were higher for males than for females. The SIR was increased to 6.22 or 30.20 when parental age was limited to 50 or 20 years, respectively. Graves' disease associated with 19 other autoimmune and related conditions, including Addison's disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia, polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and localized scleroderma. Remarkably, there was a high disease concordance of 2.75 between spouses. The clustering between spouses suggests environmental effects on Graves' disease which may contribute to the observed gender effects. The demonstrated high risks should be considered in clinical counseling and in prevention plans.
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