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Sökning: WFRF:(Hemminki Akseli)

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  • Kanerva, Anna, et al. (författare)
  • Case-control estimation of the impact of oncolytic adenovirus on the survival of patients with refractory solid tumors.
  • 2015
  • Ingår i: Molecular Therapy. - Nature Publishing Group. - 1525-0024. ; 23:2, s. 321-329
  • Tidskriftsartikel (refereegranskat)abstract
    • Oncolytic immunotherapy with cytokine armed replication competent viruses is an emerging approach in cancer treatment. In a recent randomized trial an increase in response rate was seen but the effect on overall survival is not known with any virus. To facilitate randomized trials, we performed a case-control study assessing the survival of 270 patients treated in an Advanced Therapy Access Program (ATAP), in comparison to matched concurrent controls from the same hospital. The overall survival of all virus treated patients was not increased over controls. However, when analysis was restricted to GMCSF-sensitive tumor types treated with GMSCF-coding viruses, a significant improvement in median survival was present (From 170 to 208 days, P = 0.0012, N=148). An even larger difference was seen when analysis was restricted to good performance score patients (193 versus 292 days, P = 0.034, N=90). The survival of ovarian cancer patients was especially promising as median survival nearly quadrupled (P = 0.0003, N=37). These preliminary data lend support to initiation of randomized clinical trials with GMCSF-coding oncolytic adenoviruses.Molecular Therapy (2014); doi:10.1038/mt.2014.218.
  • Chattopadhyay, Subhayan, et al. (författare)
  • Risk of second primary cancer following myeloid neoplasia and risk of myeloid neoplasia as second primary cancer : a nationwide, observational follow up study in Sweden
  • 2018
  • Ingår i: The Lancet Haematology. - Elsevier. - 2352-3026. ; 5:8, s. 368-377
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers—ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer—to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors. Methods: Using the Swedish Family-Cancer Database, we identified 35 928 individuals with primary myeloid cancer, including myeloproliferative neoplasms, acute myeloid leukaemia, chronic myeloid leukaemia, and myelodysplastic syndrome diagnosed between 1958 and 2015. The Swedish Family-Cancer Database includes every individual registered as a resident in Sweden starting in 1932, with full parental history. The primary endpoint was the assessment of relative risks (RRs) for second primary cancer, which we performed using means of incidence rate ratios, regressed over a generalised Poisson model. Findings: Between 1958 and 2015, overall relative risk of second primary cancers was significantly increased after acute myeloid leukaemia (RR 1·29, 95% CI 1·17–1·41), chronic myeloid leukaemia (1·52, 1·35–1·69), myelodysplastic syndrome (1·42, 1·26–1·59), and all myeloproliferative neoplasms (1·37, 1·30–1·43) relative to the incidence of these cancers as first primary cancer. With myeloid neoplasia as a second primary cancer, risks were significantly increased for acute myeloid leukaemia (1·57, 1·48–1·65), chronic myeloid leukaemia (1·26, 1·13–1·40), and myelodysplastic syndrome (1·54, 1·42–1·67) relative to the incidence of these myeloid neoplasms as first primary cancers. Relative risk of upper aerodigestive tract cancer, squamous cell skin cancer, and non-Hodgkin lymphoma as second primary cancers were increased after all four types of myeloid neoplasia relative to their incidence as first primary cancers. High risks of myelodysplastic syndrome and acute myeloid leukaemia as second primary cancers were found after haematological cancers (RRs between 5·08 and 10·04). Interpretation: The relative risks of second primary cancer are important for the long-term management of patients with myeloid cancers. The bi-directional associations of myeloid cancers with many other cancers suggest a number of candidate mechanisms that might contribute to the development and aetiology of a second primary cancer. These mechanisms might include immune dysfunction or the effects of treatment, and these should be assessed in future investigations. Funding: Deutsche Krebshilfe, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, Swedish Research Council, ALF from Region Skåne, and Bloodwise.
  • Chattopadhyay, Subhayan, et al. (författare)
  • Second primary cancers in non-Hodgkin lymphoma : Bidirectional analyses suggesting role for immune dysfunction
  • 2018
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 143:10, s. 2449-2457
  • Tidskriftsartikel (refereegranskat)abstract
    • Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833 individuals with primary NHL diagnosed between 1993 and 2015. We calculated relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis, risk of NHL as SPC. The overall RRs were significantly bidirectionally increased for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper aerodigestive tract (RR = 1.96), colorectal (1.35), kidney (3.10), bladder (1.54) and squamous cell skin cancer (SCC) (4.12), melanoma (1.98) and Hodgkin lymphoma (9.38). The concordance between RRs for each bidirectional association between NHL and 31 different cancers was highly significant (r = 0.86, p < 0.0001). Melanoma was bidirectionally associated with all 10 subtypes of NHL. The observed bidirectional associations between NHL and cancer suggest that therapy-related carcinogenic mechanisms cannot solely explain the findings. Considering that skin SCC and melanoma are usually treated by surgery and that these cancers and NHL are most responsive of any cancer to immune suppression, the consistent bidirectional results provide population-level evidence that immune suppressed state is a key underlying mechanism in the context of SPCs. Furthermore, the quantified risks for NHL subtypes have direct clinical application in the management of NHL patients.
  • Chattopadhyay, Subhayan, et al. (författare)
  • Second primary cancers in non-Hodgkin lymphoma : Family history and survival
  • 2020
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 146:4, s. 970-976
  • Tidskriftsartikel (refereegranskat)abstract
    • Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses and family history of cancer may be a risk factor for SPCs. Using the Swedish Family-Cancer Database on non-Hodgkin lymphoma (NHL), we assessed the influence of family history on risk of SPCs and of SPCs on survival. NHL patients were identified from the years 1958 to 2015 and generalized Poisson models were used to calculate relative risks (RRs) for SPCs and familial SPCs. Among 14,393 NHL patients, a total of 1,866 (13.0%) were diagnosed with SPC. Familial risk of nine particular cancers was associated with risks of these cancers as SPCs, with twofold to fivefold increase in RRs. At the end of a 25-year follow-up period, the survival probability for persons with SPC was only 20% of that for patients without SPC; the hazard ratio for SPC was 1.59 (95% CI: 1.46–1.72). Survival could be predicted by the prognostic groups based on first cancers and HRs increase systematically with worse prognosis yielding a trend of p = 4.6 × 10 −5 . SPCs had deleterious consequences for survival in NHL patients. Family history was associated with increasing numbers of SPCs. Prevention of SPCs and their early detection is an important target in the overall strategy to improve survival in NHL patients. Counseling for avoidance of risk factors and targeted screening based on family history are feasible steps in risk reduction.
  • Chattopadhyay, Subhayan, et al. (författare)
  • Second Primary Cancers in Patients with Invasive and In Situ Squamous Cell Skin Carcinoma, Kaposi Sarcoma, and Merkel Cell Carcinoma : Role for Immune Mechanisms?
  • 2020
  • Ingår i: Journal of Investigative Dermatology. - Elsevier. - 0022-202X. ; 140:1, s. 48-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Second primary cancers (SPCs) are becoming a common cancer entity, which may interfere with survival in relatively benign first primary cancers. We examined the hypothesis that immune dysfunction may contribute to SPCs by assessing SPCs associated with known immune responsive skin cancers, invasive and in situ squamous cell carcinoma, Kaposi sarcoma, and Merkel cell carcinoma. Cancers were identified from the Swedish Cancer Registry from the year 1958 to 2015. Standardized relative risks were calculated bidirectionally for any SPC after skin cancer and for skin cancer as SPC. Over 80,000 first primary cancers were identified for each invasive and in situ squamous cell carcinoma of the skin. Bidirectional increased risks were observed for 26 cancers associated with invasive skin cancer; the Spearman rank correlation was 0.72 (P = 4.6 × 10–5). The highest bidirectional relative risks were for invasive and in situ skin cancer as SPCs (14.59 and 16.71, respectively). Remarkably high risks for second in situ squamous cell carcinoma of the skin were found after Kaposi sarcoma (685.68) and Merkel cell carcinoma (117.23). The high systematic bidirectional risks between immune responsive skin cancers and most other cancers suggest that immune suppression is a key mechanism contributing to an increased risk of SPCs.
  • Frank, Christoph, et al. (författare)
  • Concordant and discordant familial cancer : Familial risks, proportions and population impact
  • 2017
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 140:7, s. 1510-1516
  • Tidskriftsartikel (refereegranskat)abstract
    • Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.
  • Frank, Christoph, et al. (författare)
  • Familial Associations Between Prostate Cancer and Other Cancers
  • 2017
  • Ingår i: European Urology. - Elsevier. - 0302-2838. ; 71:2, s. 162-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer (PCa) has a large familial component, but understanding of its genetic basis is fragmentary. Breast cancers may be associated with PCa, but whether this is true for other tumor types is poorly established. We used a novel approach to study familial associations of any type of cancer with PCa. We assessed the relative risk (RR) for all types of tumors as a function of the number of first-degree relatives diagnosed with PCa. We hypothesized that for a familial association to be real, the RR for a given type of cancer should increase with the number of PCa diagnoses. In families with multiple PCa patients, significantly increased risks were observed for female breast cancer (RR 1.37 for families with three men with PCa), kidney cancer (RR 2.32), nervous system tumors (RR 1.77; RR 2.40 when PCa was diagnosed before age 70 yr), and myeloma (RR 2.44; RR 6.29 when PCa was diagnosed before age 70 yr). Some evidence of association was also found for melanoma (RR 1.82) and endocrine tumors (RR 2.18). The consistency and magnitude of the effects suggest that familial PCa is genetically associated with breast, kidney, and nervous system tumors and myeloma. This suggestion has implications for clinical counseling and design of genetic studies. Patient summary: It is known that prostate cancer runs in families, but it is not known whether other cancers are common in such families. We showed that at least breast, kidney, and nervous system tumors and myeloma occur more often than by chance. The present results demonstrate that prostate cancer (PCa) families show a statistical excess of some defined cancers. The cancers associated with PCa include breast, kidney, and nervous system tumors and myeloma and possibly melanoma and endocrine tumors.
  • Frank, Christoph, et al. (författare)
  • Risk of other Cancers in Families with Melanoma : Novel Familial Links
  • 2017
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A family history of cutaneous melanoma ('melanoma') is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.
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