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1.
  • Aasebo, Kristine, et al. (författare)
  • CDX2 A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup
  • 2020
  • Ingår i: Frontiers in Oncology. - FRONTIERS MEDIA SA. - 2234-943X .- 2234-943X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.
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2.
  • Aasebö, Kristine Ö., et al. (författare)
  • Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors A population-based cohort of metastatic colorectal cancer patients
  • 2019
  • Ingår i: Cancer Medicine. - WILEY. - 2045-7634 .- 2045-7634. ; 8:7, s. 3623-3635
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).
3.
  • Adami, Hans-Olov, et al. (författare)
  • Pregnancy and risk of non-Hodgkin´s lymphoma : a prospective study
  • 1997
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 70:2, s. 155-158
  • Tidskriftsartikel (refereegranskat)abstract
    • The etiology of non-Hodgkin's lymphomas (NHL), including chronic lymphocytic leukemia (CLL), is likely to be related to immune function. In the light of the established immunologic effects of a pregnancy, we decided to examine the risk of NHL and CLL in relationship to full-term pregnancies. Within a nationwide cohort we identified 1,546 women with NHL and 198 women with CLL, all 15 years or older, born 1925-1972. Five age-matched controls were selected for each case patient. Conditional logistic regression was used to estimate the odds ratios after mutual adjustment for number of births and age at first birth. We found a weak, negative association between parity and risk of NHL (p for trend 0.11) and a transient, 10-40% decrease in risk within 5-14 years after the last birth among women with various parity status. The risk of CLL decreased more markedly, and orderly with increasing parity, but the trend was not significant (p = 0.18). Small numbers of cases with CLL prevented more detailed analyses of temporal relationships. Age at first birth appeared unrelated to the risk of both NHL and CLL. We conclude that the immunologic alterations associated with a pregnancy have limited, if any, relevance to the etiology of NHL and CLL; changing reproductive pattern is an unlikely contributor to the marked increase in incidence of NHL seen in many populations.
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4.
  • Adami, Johanna, et al. (författare)
  • Blood transfusion and non-Hodgkin lymphoma: : Lack of association
  • 1997
  • Ingår i: ANNALS OF INTERNAL MEDICINE. - AMER COLL PHYSICIANS. - 0003-4819. ; 127:5, s. 365-&
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant condition worldwide, and its incidence has increased markedly in recent decades. Blood transfusions have been implicated as a possible risk factor for non-Hodgkin lymphoma. OBJECTIVE: To determine whether blood transfusions are associated with an elevated risk for non-Hodgkin lymphoma. DESIGN: Population-based, nested case-control study. SETTING: Nationwide cohort in Sweden. PATIENTS: 361 patients with non-Hodgkin lymphoma and 705 matched controls, nested within a population-based cohort of 96795 patients at risk for blood transfusion between 1970 and 1983. Prospectively collected information on exposure was retrieved from computerized transfusion registries. MEASUREMENTS: Odds ratios obtained from conditional logistic regression models were used as measures of relative risks. RESULTS: No association was found between blood transfusions and the risk for non-Hodgkin lymphoma when patients who had received transfusions were compared with patients who had not received transfusions (odds ratio, 0.93 [95% CI, 0.71 to 1.23]). A reduction in risk was seen among persons who received transfusion of blood without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not related to number of transfusions, and no interaction was seen with latency after transfusion. CONCLUSION: The findings in this study do not support previous observations of an association between blood transfusions and the risk for non-Hodgkin lymphoma.
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5.
  • Adami, Johanna, et al. (författare)
  • Cancer risk following organ transplantation : a nationwide cohort study in Sweden
  • 2003
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 89:7, s. 1221-1227
  • Tidskriftsartikel (refereegranskat)abstract
    • A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970-1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7-4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8-63.2), lip cancer (SIR 53.3; 95% CI 38.0-72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4-8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3-16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.
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6.
  • Adami, Johanna, et al. (författare)
  • Evidence of an association between non-Hodgkin´s lymphoma and skin cancer
  • 1995
  • Ingår i: BMJ (Clinical research ed.). - 0959-8138. ; 310:6993, s. 1491-1495
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE--To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkin's lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non-Hodgkin's lymphoma and skin cancer was studied. DESIGN--Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. SETTING--Denmark (1943-89) and Sweden (1958-89). SUBJECTS--Four population based cohorts identified in the nationwide cancer registries (34,641 people with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukaemia, 34,989 with malignant melanoma, 25,980 with squamous cell skin cancer). A total of 562,085 person years were accrued for the analysis. MAIN OUTCOME MEASURES--The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. RESULTS--The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non-Hodgkin's lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non-Hodgkin's lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. CONCLUSIONS--The occurrence of non-Hodgkin's lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkin's lymphoma in recent decades.
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7.
  • Adami, Johanna, et al. (författare)
  • Maternal and perinatal factors associated with non-Hodgkin's lymphoma among children
  • 1996
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 65:6, s. 774-777
  • Tidskriftsartikel (refereegranskat)abstract
    • This nested case-control study based on 1.7 million live births in Sweden explores the associations between maternal and perinatal factors and the occurrence of childhood non-Hodgkin's lymphoma (NHL). The National Swedish Cancer Registry ascertained 168 cases in successive birth cohorts from 1973 through 1989 recorded in the Swedish Medical Birth Registry. From the nationwide Birth Registry, 5 controls without NHL and alive at the date the case was diagnosed were randomly selected from the pool of children, with each case matched by gender, birth year and birth month. Standardized information on selected maternal and perinatal factors up to one month after delivery were recorded in the Medical Birth Registry. Mothers of children with NHL were more likely than mothers of controls to have undergone Cesarean section [Odds ratio (OR) 1.6] and to have been exposed to paracervical anesthesia during delivery (OR 1.8). Children with NHL were more likely than controls to have endocrine-metabolic disorders (OR 3.3). This study is one of the largest focusing on the etiology of childhood NHL. Most of the maternal and perinatal characteristics studied did not markedly affect risk for childhood NHL, which may be due to maternal and perinatal factors not included in these data or to exposures later in life.
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8.
  • Adami, Johanna, et al. (författare)
  • Smoking and the risk of leukemia, lymphoma, and multiple myeloma (Sweden)
  • 1998
  • Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 9:1, s. 49-56
  • Tidskriftsartikel (refereegranskat)abstract
    • While several epidemiologic studies have indicated a link between smoking and the risk of developing hematolymphoproliferative cancers (chiefly leukemias, lymphomas, and multiple myelomas), in particular myeloid leukemia, the role of tobacco in the etiology of these neoplasms remains unclear. To evaluate the potential impact of tobacco use on development of leukemia, lymphoma, and multiple myeloma, we conducted a cohort study of 334,957 Swedish construction workers using prospectively collected exposure-information with complete long-term follow-up. A total of 1,322 incident neoplasms occurred during the study period, 1971-91. We found no significant association between smoking status, number of cigarettes smoked, or duration of smoking and the risk of developing leukemias, lymphomas, or multiple myeloma. There was a suggestion of a positive association between smoking and the risk of developing Hodgkin's disease, although the rate ratios were not significantly elevated, except for young current smokers. No positive dose-risk trends emerged. Our study provides no evidence that smoking bears any major relationship to the occurrence of leukemias, non-Hodgkin's lymphomas, or multiple myeloma.
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9.
  • Adami, Johanna, et al. (författare)
  • Sunlight and non-Hodgkin's lymphoma : a population-based cohort study in Sweden
  • 1999
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 80:5, s. 641-645
  • Tidskriftsartikel (refereegranskat)abstract
    • Indirect evidence, notably ecological comparisons and an association with skin cancer, links non-Hodgkin's lymphoma (NHL) with exposure to sunlight. We conducted a population-based, nationwide cohort study with exposure to outdoor work inferred from job titles reported in the population and housing censuses in 1960 and/or 1970 and by classifying each individual's work and home addresses according to latitude. Follow-up for cancer incidence was accomplished through record linkages with the virtually complete Swedish Cancer Registry. The cohort included all Swedish residents who were recorded as gainfully employed in both censuses. Altogether 4,171,175 individuals contributing 69,639,237 person-years accrued through 1989 were included in the analyses. We identified 10,381 cases of NHL, 4,018 cases of chronic lymphocytic leukemia (CLL), 11,398 cases of malignant melanoma (MM) and 11,913 cases of squamous cell skin cancer (SCC). We calculated age-adjusted relative risks for NHL, CLL, MM and SCC in strata based on estimated residential and occupational sunlight exposure. Interaction effects were considered for pesticide and solvent exposure. NHL, MM and SCC, but not CLL, were positively associated with increasingly southerly residential latitude, with stronger associations seen for skin cancer compared to NHL. Occupational sun exposure was not associated with the risk of developing any of the studied cancers. Pesticides and solvents also were not related to an increased risk of NHL, nor did these exposures enhance effects of residential or occupational sunlight exposure. Our results provide some support for an association of sunlight exposure with NHL incidence based on the associations seen using geographic latitude of residence as a proxy for exposure. Although type of occupation may be an imperfect index of the biologically relevant ultraviolet (UV) light dose, our data on individual exposure are not consistent with an important role of sunlight in the etiology of NHL.
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10.
  • Aldulaymi, Bahir, et al. (författare)
  • High Plasma TIMP-1 and Serum CEA Levels during Combination Chemotherapy for Metastatic Colorectal Cancer Are Significantly Associated with Poor Outcome
  • 2010
  • Ingår i: Oncology. - 0030-2414 .- 1423-0232. ; 79:1-2, s. 144-149
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival. Materials and Methods: Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy. Results: Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP- 1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment. Conclusion: Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.
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