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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) srt2:(2000-2004);srt2:(2000)"

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  • Kaerlev, L., et al. (författare)
  • Occupation and small bowel adenocarcinoma : A European case-control study
  • 2000
  • Ingår i: Occupational and environmental medicine. - BMJ Publishing Group. - 1351-0711. ; 57:11, s. 760-766
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives - Because of the rarity of small bowel adenocarcinoma (SBA), little is known about the aetiology of this disease. This study aimed to identify occupational clustering of cases SBA as a systematic approach to new hypotheses on the aetiology of this disease. Methods - A European multicentre case-control study was conducted in 1995-7, inclusive. Incident cases aged 35-69 years with SBA (n=168) were recruited before acceptance by a pathologist. Altogether 107 cases and 3915 controls were accepted, of which 79 cases, 579 colon cancer controls, and 2070 population controls were interviewed. Results - The strongest industrial risk factors for SBA taking account of 10 years' exposure lag were dry cleaning, manufacture of workwear, mixed farming (women), and manufacture of motor vehicles (men). A significantly increased risk of SBA (odds ratio (OR) and 95% confidence interval (95% CI)) was found among men employed as building caretakers, OR 6.7 (1.7 to 26.0) and women employed as housekeepers, OR 2.2 (1.1 to 4.9); general farm labourers, OR 4.7 (1.8 to 12.2); dockers, OR 2.9 (1.0 to 8.2); dry cleaners or launderers, OR 4.1 (1.2 to 13.6); and textile workers (sewers or embroiders), OR 2.6 (1.0 to 6.8). For the last four groups, together with welders OR 2.7 (1.1 to 6.6) (men) an exposure-response pattern was found when calculating the ORs for jobs held 1-5 years and >5 years, with never having held the job as reference. The ORs (95% CIs) for 1-5 years and >5 years were 4.3 (0.4 to 44.0) and 3.5 (0.9 to 13.7), 3.0 (0.3 to 26.2) and 4.3 (0.9 to 21.2), 4.6 (0.4 to 48.1) and 11.0 (2.0 to 60.4), 1.3 (0.2 to 11.0) and 5.8 (2.0 to 17.2), and 2.8 (0.3 to 23.8) and 4.6 (1.3 to 16.6), respectively, for each of these occupations. Among welders, people performing semi-automatic arc welding (MIG/MAG) were identified as a high risk group (OR 5.0 (1.3 to 19.6)). Conclusions - This explorative study suggests an increased occurrence of SBA in certain occupations, which needs further evaluation.
  • Kainu, T, et al. (författare)
  • Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus
  • 2000
  • Ingår i: Proceedings of the National Academy of Sciences. - National Acad Sciences. - 1091-6490. ; 97:17, s. 9603-9608
  • Tidskriftsartikel (refereegranskat)abstract
    • A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.
  • Kauraniemi, P, et al. (författare)
  • MYB oncogene amplification in hereditary BRCA1 breast cancer
  • 2000
  • Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 1538-7445. ; 60:19, s. 5323-5328
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.
  • Khan, Tanweera Shaheena, et al. (författare)
  • Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients : long-term survival in its adjuvant use
  • 2000
  • Ingår i: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 11:10, s. 1281-1287
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong></p><p>To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects.</p><p><strong>PATIENTS AND METHODS:</strong></p><p>We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin.</p><p><strong>RESULTS:</strong></p><p>The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02).</p><p><strong>CONCLUSIONS:</strong></p><p>The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.</p>
  • Koul, A., et al. (författare)
  • BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
  • 2000
  • Ingår i: International Journal of Gynecological Cancer. - Wiley-Blackwell. - 1048-891X. ; 10:4, s. 289-295
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
  • Lagerlund, M, et al. (författare)
  • Predictors of non-attendance in a population-based mammography screening programme; socio-demographic factors and aspects of health behaviour
  • 2000
  • Ingår i: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 9:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The aim of this study was to identify predictors of non-attendance in a population-based mammography-screening programme in central Sweden, on the basis of telephone interviews with 434 non-attendees and 515 attendees identified in a mammography register, Non-attendance was studied in relation to sociodemographic factors, indicators of general health behaviour, self-rated health and experience of cancer in others and own cancer or breast problems. Being single or being non-employed were the only important socio-demographic predictors of non-attendance. Non-attendance was more likely among women who never visited a dentist, had not visited a doctor in 5 years, had never used oral contraceptives or hormone replacement therapy, had never had cervical smear tests, never drank alcohol, smoked regularly, reported no breast cancer in family or friends or own breast problems, We conclude that socio-demographic factors alone do not appear to constitute strong predictors of non-attendance, General health behaviour and previous experience of cancer and breast disease seem to be more important factors. Our results suggest that in the setting of population-based outreach mammography programmes, previous contacts with the health care system and encouragement from health professionals represent determinants of attendance.</p>
  • Loman, Niklas, et al. (författare)
  • Prognosis and clinical presentation of BRCA2-associated breast cancer
  • 2000
  • Ingår i: European Journal of Cancer. - Elsevier. - 1879-0852. ; 36:11, s. 1365-1373
  • Tidskriftsartikel (refereegranskat)abstract
    • 54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRCA2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRCA2 germ line mutations.
  • Lord, R V, et al. (författare)
  • Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence
  • 2000
  • Ingår i: Journal of Gastrointestinal Surgery. - Springer. - 1091-255X. ; 4:2, s. 42-135
  • Tidskriftsartikel (refereegranskat)abstract
    • Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.
  • Lundström, Staffan, et al. (författare)
  • Aspects of delayed chemotherapy-induced nausea : Dexamethasone and adrenal response patterns in patients and healthy volunteers
  • 2000
  • Ingår i: Supportive Care in Cancer. - Springer. - 0941-4355 .- 1433-7339. ; 8:5, s. 431-434
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their anti-emetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.</p>
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