1. |
- Eriksson, Louise, et al.
(author)
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Time from breast cancer diagnosis to therapeutic surgery and breast cancer prognosis : A population-based cohort study
- 2018
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In: International Journal of Cancer. - Stockholm : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:5, s. 1093-1104
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Journal article (peer-reviewed)abstract
- Theoretically, time from breast cancer diagnosis to therapeutic surgery should affect survival. However, it is unclear whether this holds true in a modern healthcare setting in which breast cancer surgery is carried out within weeks to months of diagnosis. This is a population- and register-based study of all women diagnosed with invasive breast cancer in the Stockholm-Gotland healthcare region in Sweden, 2001-2008, and who were initially operated. Follow-up of vital status ended 2014. 7,017 women were included in analysis. Our main outcome was overall survival. Main analyses were carried out using Cox proportional hazards models. We adjusted for likely confounders and stratified on mode of detection, tumor size and lymph node metastasis. We found that a longer interval between date of morphological diagnosis and therapeutic surgery was associated with a poorer prognosis. Assuming a linear association, the hazard rate of death from all causes increased by 1.011 (95% CI 1.006-1.017) per day. Comparing, for example, surgery 6 weeks after diagnosis to surgery 3 weeks after diagnosis, thereby confers a 1.26-fold increased hazard rate. The increase in hazard rate associated with surgical delay was strongest in women with largest tumors. Whilst there was a clear association between delays and survival in women without lymph node metastasis, the association may be attenuated in subgroups with increasing number of lymph node metastases. We found no evidence of an interaction between time to surgery and mode of detection. In conclusion, unwarranted delays to primary treatment of breast cancer should be avoided. What's new? Theoretically, an increase in the interval between breast-cancer diagnosis and therapeutic surgery should affect survival, but it is uncertain whether that holds true in a modern healthcare setting. In this prospective study, the authors found that even fairly short delays (on the order of days or weeks) from diagnosis to surgery are associated with decreased survival. These results suggest that the time between diagnosis and therapeutic surgery should be kept as short as possible without hampering diagnostic work-up and preoperative patient optimization.
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2. |
- Wennerberg, Erik, et al.
(author)
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Doxorubicin sensitizes human tumor cells to NK and T cell-mediated killing by augmented TRAIL-receptor signaling
- 2013
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In: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1097-0215 .- 0020-7136.
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Journal article (other academic/artistic)abstract
- Doxorubicin (DOX) is an anthracycline antibiotic that is widely used to treat different types of malignancy. In this study, it was studied whether DOX could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with subapoptotic doses of DOX sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7% increase in lysis (2.5 mean fold increase, p < 0.0001) and a 2.9 to 14.2% increase in lysis (3.0 mean-fold increase, p < 0.05), respectively. The sensitizing effect of the drug was primarily dependent on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptor signaling, but not on Fas-ligand, perforin, NKG2D or DNAM-1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL-R2 on DOX-treated tumor cells and by downregulation of cellular FLICE inhibitory protein, the inhibitors of death receptor-mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with DOX showed increased processing and activation of caspase-8 on coculture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor-bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p < 0.05) or T cells (p < 0.0001) following DOX treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following DOX treatment not only delayed tumor progression but also significantly improved the long-term survival (p < 0.01). Based on these findings, it was proposed that DOX can be used to improve the efficacy of adoptive cell therapy in patients with cancer.
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3. |
- Xie, Shao-Hua, et al.
(author)
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A possible link between famine exposure in early life and future risk of gastrointestinal cancers : implications from age-period-cohort analysis
- 2016
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In: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1097-0215 .- 0020-7136.
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Journal article (peer-reviewed)abstract
- The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71 ,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer, and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal, and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver, and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver, and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.
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4. |
- Gentile, Massimiliano, et al.
(author)
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Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer
- 2001
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 92:2, s. 208-213
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Journal article (peer-reviewed)abstract
- Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.
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5. |
- Bergström, A, et al.
(author)
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Overweight as an avoidable cause of cancer in Europe
- 2001
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 91:3, s. 421-30
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Journal article (peer-reviewed)abstract
- There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.
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6. |
- Bergström, A., et al.
(author)
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Physical activity and risk of renal cell cancer
- 2001
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In: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 92:1, s. 155-157
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Journal article (peer-reviewed)abstract
- The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.
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7. |
- Cederquist, Kristina, et al.
(author)
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A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) staus, age at diagnosis and cancer risk
- 2001
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 91:4, s. 486-491
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Journal article (peer-reviewed)abstract
- Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described. Copyright 2001 Wiley-Liss, Inc.
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8. |
- Michels, Karin B., et al.
(author)
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Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women
- 2001
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 91:4, s. 563-567
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Journal article (peer-reviewed)abstract
- Dietary antioxidant vitamins and retinol have been proposed to be protective against breast cancer on the basis of their ability to reduce oxidative DNA damage and their role in cell differentiation. Epidemiologic studies have not been convincing in supporting this hypothesis, but women with high exposure to free radicals and oxidative processes have not been specifically considered. We explored these issues in the Swedish Mammography Screening Cohort, a large population-based prospective cohort study in Sweden that comprised 59,036 women, 40-76 years of age, who were free of cancer at baseline and who had answered a validated 67-item food frequency questionnaire. During 508,267 person-years of follow-up, 1,271 cases of invasive breast cancer were diagnosed. Cox proportional hazards models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). There was no overall association between intake of ascorbic acid, beta-carotene, retinol or vitamin E and breast cancer incidence. High intake of ascorbic acid was inversely related to breast cancer incidence among overweight women (HR=0.61; 95% CI 0.45-0.82, for highest quintile of intake among women with body mass index>25 kg/m(2)) and women with high consumption of linoleic acid (HR=0.72; 95% CI 0.52-1.02, for highest quintile of ascorbic acid intake and average consumption of more than 6 grams of linoleic acid per day). Among women with a body mass index of 25 or below, the hazard ratio for breast cancer incidence was 1.27 (95% CI 0.99-1.63), comparing the highest to the lowest quintile of ascorbic acid intake. Consumption of foods high in ascorbic acid may convey protection from breast cancer among women who are overweight and/or have a high intake of linoleic acid.
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9. |
- Gustafsson, Leif, et al.
(author)
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International incidence rates of invasive cervical cancer before cytological screening
- 1997
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 71:2, s. 159-165
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Journal article (peer-reviewed)abstract
- Huge differences in incidence rates of invasive cervical cancer occur among populations. These differences reflect the influences of both etiological environmental factors and removal of precursor lesions detected upon screening. The purposes of this article are (i) to describe similarities and differences in the shapes and magnitudes of age-specific incidence rates of invasive cervical cancer before screening had an effect, (ii) to provide baseline data for further global study of screening effects, and (iii) to provide baseline incidence data for the design of optimal screening programs. To eliminate the impact of screening effects, we have selected age-specific incidence rates from times when and from populations in which screening was insignificant. The selected rates were suitably scaled and compared regarding age at onset of increase in incidence, age at peak incidence, and rate of subsequent decline. Despite a 16-fold difference in incidence rates, all curves had the same basic structure, with an increase to a peak followed by a decline or a plateau. Although all populations but one had an onset around age 25, 7 European countries showed an earlier peak age (mean = 46 vs. 59) and a more rapid decline after the peak than most other populations. The common basic shape of the age-specific incidence curve, overall, suggests a relatively similar development of invasive cervical cancer in different populations. These results illustrate the underlying similarities in the markedly different age-specific incidence rates of invasive cervical cancer. They also provide a basis for studying screening effects and for optimizing screening programs in specific geographic areas.
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10. |
- Smith-Warner, S A, et al.
(author)
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Types of dietary fat and breast cancer : a pooled analysis of cohort studies
- 2001
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 92:5, s. 767-74
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Journal article (peer-reviewed)abstract
- Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.
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11. |
- Adami, Hans-Olov, et al.
(author)
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Pregnancy and risk of non-Hodgkin´s lymphoma : a prospective study
- 1997
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 70:2, s. 155-158
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Journal article (peer-reviewed)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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12. |
- Akre, Olof, et al.
(author)
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Epstein-Barr virus and cytomegalovirus in relation to testicular-cancer risk : a nested case-control study
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 82:1, s. 1-5
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Journal article (peer-reviewed)abstract
- An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.
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13. |
- Amini, Rose-Marie, et al.
(author)
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Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients
- 1997
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 71, s. 510-
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Journal article (peer-reviewed)abstract
- The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.
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14. |
- Bergman-Jungeström, Malin, 1967-, et al.
(author)
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Association between CYP17 gene polymorphism and risk of breast cancer in young women
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 84, s. 350-353
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Journal article (peer-reviewed)abstract
- Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T→C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1–3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1.9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41–1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women.
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15. |
- Bergström, A., et al.
(author)
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Occupational physical activity and renal cell cancer : a nationwide cohort study in Sweden
- 1999
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In: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 83:2, s. 186-91
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Journal article (peer-reviewed)abstract
- The causes of renal cell cancer remain incompletely understood. In one previous retrospective case-control study, high occupational physical activity has been associated with a decreased risk among men, but not among women. Our aim was to investigate the association between occupational physical activity and renal cell cancer in a large cohort in Sweden. A cohort of Swedish men and women was identified in the nationwide censuses in 1960 and 1970, and the reported occupations were classified into 4 levels of physical demands. Follow-up from 1971 through 1989 was accomplished through record linkages to the Swedish Cancer Registry. Multivariate Poisson regression models were used to estimate relative risk (RR) and 95% confidence intervals (CI). We found a monotonic increase in risk of renal cell cancer with decreasing level of occupational physical activity among men (p for trend <0.001). After adjustment for socio-economic status, place of residence, and calendar year of follow-up, men with long-term sedentary jobs had a 25% (RR = 1.25, 95% CI 1.02-1.53) increased risk compared to men with physically demanding occupations. Among women there was no association, the dose-risk trend was not significant (p for trend >0.50). Occupational physical activity was inversely associated with renal cell cancer among men. The absence of association among women might be due to smaller range of exposure, confounding by household work or reproductive factors, or to a difference in biological response to physical activity in men and women.
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16. |
- de Witte, H H, et al.
(author)
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Prognostic significance of TP53 accumulation in human primary breast cancer : comparison between a rapid quantitative immunoassay and SSCP analysis.
- 1996
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 69:2, s. 125-130
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Journal article (peer-reviewed)abstract
- TP53 accumulation in human primary breast carcinomas was studied by a quantitative luminometric immunoassay (LIA), and TP53 gene alterations, exons 5-8, were examined by single-strand conformation polymorphism (SSCP) analysis. In 48 of 142 breast tumor samples, a TP53 gene alteration was identified. In tumor samples without a TP53 gene alteration, the median cytosolic TP53 protein level, as determined by LIA, was 0.4 ng/mg protein (range 0-70.8 ng/mg protein), whereas the median TP53 protein level for tumor samples with a TP53 gene alteration was 10 times higher, i.e., 4.1 ng/mg protein (range 0.1-176.0 ng/mg protein). Despite a significant correlation between the outcome of LIA and SSCP, a disagreement was found in 22% of cases analyzed. Significant correlations were found between TP53 protein accumulation and low estrogen receptor content, and with a shorter relapse-free as well as overall survival, with a median duration of follow-up of 100 months. Due to its rapid and easy performance on routinely prepared cytosols, the LIA for TP53 protein may be useful in evaluating the prognostic impact of TP53 protein accumulation in human primary breast cancer.
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17. |
- Fulda, S., et al.
(author)
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Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system
- 1998
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 76:1, s. 105-114
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Journal article (peer-reviewed)abstract
- We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system, Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')(2) anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis, Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis, The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases, Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors. (C) 1998 Wiley-Liss, Inc.
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18. |
- Granberg, Dan, et al.
(author)
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Decreased survival in patients with CD44-negative typical bronchial carcinoid tumors
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 84:5, s. 484-488
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Journal article (peer-reviewed)abstract
- Tumor tissues from 43 patients with typical bronchial carcinoids have been immunostained with monoclonal antibodies (mAbs) against the standard form (CD44s) and the splice variants v4, v5, v6, v7, v7-8, v9 and v10 of the adhesion molecule CD44. The staining results were correlated with clinical data. Ten patients (23%) had regional lymph node metastases at diagnosis. Distant metastases have occurred in 12% of the patients; 9% died during the observation period of median 65 months (14-325). Positive staining for CD44s was correlated with decreased risk for distant metastases and disease related death. All patients with distant metastases were v6-negative. Patients with CD44v7-8-positive tumors had decreased risk for distant metastases, but the differences in mortality did not reach statistical significance. CD44v9 correlated significantly with decreased risk for distant metastases and death. The remaining CD44 variants (v4, v5 and v10) did not correlate significantly with clinical outcome. Our results confirm earlier observations that typical bronchial carcinoids are potentially malignant. However, positive staining for CD44s, v7-8 and v9 seems to be associated with a more favorable outcome, and may be taken into consideration in prognostic evaluation.
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19. |
- Hjalgrim, Henrik, et al.
(author)
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Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma
- 2000
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 85:5, s. 639-642
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Journal article (peer-reviewed)abstract
- According to recent results, patients with non-melanoma skin cancers are at increased risk of developing non-Hodgkin's lymphoma (NHL). The prognostic significance of this association is unknown. Two cohorts of patients with a first diagnosis of non-melanoma skin cancer and a subsequent diagnosis of either NHL (n = 170) or colon cancer (n = 435) were established using national cancer registry data in Denmark. Two other cohorts of patients in whom NHL (n = 600) or colon cancer (n = 1,541) was the patients' first known malignancy served as comparison groups. Mortality rates were compared using Cox's regression analysis. Among patients younger than 80 years at NHL diagnosis, a history of non-melanoma skin cancer was associated with significantly increased mortality [relative risk (RR) = 1.54; 95% confidence interval: 1.19-1.99]. This association was present in both men (RR = 1.38; 1.02-1.86) and women (RR = 2.15; 1.31-3.54) and was similar after both major subtypes of non-melanoma skin cancer. Overall, antedating non-melanoma skin cancer had no prognostic significance for colon cancer patients (RR = 1.00; 0.84-1.18). Whatever the underlying mechanism, our observation has potential clinical implications. If substantiated in other settings, NHL patients with prior non-melanoma skin cancer may constitute a subgroup of lymphoma patients in need of particular therapeutic attention.
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20. |
- Ibrahim, S O, et al.
(author)
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Immunohistochemical detection of p53 in non-malignant and malignant oral lesions associated with snuff dipping in the Sudan and Sweden
- 1996
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 68:6, s. 749-753
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Journal article (peer-reviewed)abstract
- Immunohistochemistry was used to examine the expression of p53 in pre-malignant oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non-snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff-dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68% (28/41) expressed p53, respectively. A statistically significant difference in expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those from non-snuff-dippers from all/or any of the 3 countries. None of the suspected pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff-dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did not. The low relative frequency of p53 expression found in oral SCCs from snuff-dippers compared to those from non-snuff-dippers might suggest differences in mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis of malignant oral lesions from snuff-dippers may follow a p53-independent pathway. In view of the unusually high levels of the tobacco-specific nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations of p53 mutations or oncogenes are needed.
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21. |
- Larsson, Erik, et al.
(author)
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Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line
- 1996
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 67:3, s. 451-456
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Journal article (peer-reviewed)abstract
- ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.
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22. |
- Norberg, Torbjörn, et al.
(author)
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Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors.
- 1998
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 79:4, s. 376-383
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Journal article (peer-reviewed)abstract
- The p53 mutational status of 226 representative primary breast cancer samples, derived from a population-based cohort, was analyzed using cDNA-based sequencing. The results were comparedwith those obtained with immunohistochemistry (IHC) on microwave-treated paraffin sections and the p53specific luminometric immunoassay (LIA) on cytosols, all from the same individuals. Thirty-sevenmutations were found using cDNA sequencing and were categorized into A) missense mutations in theevolutionarily conserved regions; B) missense mutations outside the evolutionarily regions; and C) deletions, insertions and nonsense mutations. Using optimal cut-off values, LIA detected 15 of 16 missense mutations in category A, in which IHC defected all 16. In category B, 10 of 13 and 7 of 13mutations were detected, respectively. Some of the samples in category A had a very high p53 proteincontent when measured with the LIA, the reason for this being discussed. IHC detected 0 of 5 stop codon and 0 of 3 deletions/insertions mutations, while the LIA method detected 2 of 5 stop codon mutations and Iof 3 deletion/insertion mutations. Compared with cDNA sequencing, protein analyses using optimal cut-off values resulted in an overall sensitivity and specificity of 64.9% and 89.9%, respectively, for the LIA method. Corresponding values were 72.2% and 92% for IHC. In addition, patients from whom p53mutations could be detected by cDNA sequencing had a statistically significant (p = 0.0137) shorter survival, which was not readily apparent using the alternative LIA or IHC approaches at optimal cut-off values.
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23. |
- Nordlund, Lars Anders, et al.
(author)
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Cancer incidence in female smokers : a 26-year follow-up
- 1997
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 73:5, s. 625-628
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Journal article (peer-reviewed)abstract
- A random sample of 26,000 Swedish women who were asked about their smoking habits in the early 1960s have now been followed for 26 years with respect to cancer incidence. Most findings regarding tobacco smoking and cancer from studies of men were confirmed also among the women. Elevated relative risk for current smokers compared with women who never smoked regularly were seen for cancers of the lung, upper aerodigestive sites, pancreas, bladder, cervix and all cancers combined, as well as a notably high relative risk for cancers of organs of the urinary tract other than kidney and bladder. Relative risk increased with dose, measured as grams of tobacco smoked per day, for cancers of the upper aerodigestive sites, lung, cervix, bladder, organs of the urinary tract other than kidney and bladder and all cancers combined. For cancers of the lung, bladder and cervix, there was an inverse relationship with age when starting to smoke tobacco. The reported inverse relationship between smoking and endometrial cancer could not be corroborated, nor was there any significant relationship between smoking and colorectal or breast cancer.
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24. |
- Petridou, E, et al.
(author)
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Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 80:4, s. 494-496
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Journal article (peer-reviewed)abstract
- The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.
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25. |
- Sander, B., et al.
(author)
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Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological : study of 130 cases
- 1999
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In: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 80:5, s. 646-651
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Journal article (peer-reviewed)abstract
- To assess whether there has been a change in histological features and prognostic factors of primary cutaneous malignant melanoma (CMM) in young individuals in Sweden, an unselected, population-based study was undertaken; 177 cases of primary CMM in persons below 20 years of age were reported to the Swedish National Cancer Registry between 1973 and 1992. In 87% of the cases, original tumor tissue was available for histo-pathological review. The original diagnosis was verified in 88% (n = 126) of these cases. All tumors had histological features similar to adult CMM; 17% had an associated precursor lesion. Superficial spreading melanoma (SSM) was the most common sub-type, constituting 20/36 cases in the first decade and 59/90 in the second. Corresponding figures for nodular melanoma (NM) were 11/36 and 23/90. Only 5 melanomas in situ were diagnosed. In girls, the mean thickness of SSM decreased from 1.5 to 0.6 mm (p < 0.001). Overall mortality was 10%, 22% in the group with CMM diagnosed 0-15 years of age and 8% in individuals 15-19 years. Fatal CMM cases diagnosed below 15 years of age (n = 4) were NM >1.6 mm thick and in subjects 15-19 years (n = 9) 44% of fatal tumors were NM with a mean thickness of 2.2 mm. Breslow index was the single most important prognostic factor. However, when known prognostic factors were adjusted for in a Cox regression analysis, young age remained an independent risk factor, with a relative death rate of 0.21 for individuals aged 15-19 compared with children <15 years of age.
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