| 1. |
- Hemminki, Kari, et al.
(författare)
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Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:10, s. 2720-2724
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Tidskriftsartikel (refereegranskat)abstract
- Cancer of unknown primary (CUP) is diagnosed at the metastatic stage. We aimed to identify hidden primary cancers in CUP patients by comparison with cancers in family members. We take use of the fact that the cause of death in CUP patients is often coded as the cancer in the organ of fatal metastasis. Forty-one thousand five hundred and twenty-three CUP patients were identified in the Swedish Family-Cancer Database, and relative risks (RRs) were calculated for cancer in offspring when family members were diagnosed with CUP and died of the cancer diagnosed in offspring. The RR for lung cancer in offspring was 1.85 when a family member was diagnosed with CUP and died of lung cancer. Significant familial associations were found for seven other cancers. Many familial associations were also significant when offspring CUP patients died of the cancer diagnosed in family members. The cause of death after CUP diagnosis frequently matched the cancer found in a family member, suggesting that the CUP had originated in that tissue. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These novel data suggest that some CUP cases are phenotypically modified primary cancers rather than cancers of unknown primaries.
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| 2. |
- Hemminki, Kari, et al.
(författare)
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Survival in cancer of unknown primary site: population-based analysis by site and histology
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:7, s. 1854-1863
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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.
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| 3. |
- Wang, Hui, et al.
(författare)
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A coding IRAK2 variant compromises TLR signaling and is associated with colorectal cancer survival.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:33, s. 23123-23131
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Tidskriftsartikel (refereegranskat)abstract
- Within innate immune signaling pathways, Interleukin-1 receptor (IL-1R&)-associated kinases (IRAKs) fulfill key roles downstream of multiple Toll-like receptors (TLR) and the IL-1R. Whereas human IRAK4-deficiency was shown to lead to severe immunodeficiency in response to pyogenic bacterial infection during childhood, little is known about the role of human IRAK2. We here identified a non-synonymous IRAK2 variant, rs35060588 (coding R214G), as hypofunctional in terms of NF-κB signaling and TLR-mediated cytokine induction. This was due to reduced ubiquitination of TRAF6, a key step in signal transduction. IRAK2 rs35060588 occurs in 3-9% of individuals in different ethnic groups and our studies uncovered a significant genetic association of rs35060588 with colorectal cancer survival. This for the first time firmly implicates human IRAK2 in human disease and highlights the R214G IRAK2 variant as a potential novel and broadly applicable biomarker for disease or as a therapeutic intervention point.
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