Loss of heterozygosity on chromosome 5q in ovarian cancer is frequently accompanied by TP53 mutation and identifies a tumour suppressor gene locus at 5q13.1-21.

Forty-nine ovarian tumours were examined for loss of heterozygosity (LOH) on chromosome 5 using eight microsatellite markers spanning both arms, including one at the APC locus. LOH on 5q was a frequent event, detectable in 23 of 49 (47%) tumours, whereas 5p LOH was detected in only 1 of 22 tumours (5%). Six tumours showed partial LOH on 5q, enabling the candidate region to be localised to a 22 cM region proximal to APC, flanked by D5S424 and D5S644. An association was found between 5q LOH and TP53 mutation, with 18 of 23 (78%) tumours with LOH on 5q also harbouring a TP53 mutation. LOH on 5q was observed in 6 of 18 (33%) stage I tumours, suggesting that it may be an early event in the molecular pathogenesis of certain ovarian carcinomas.     

Positive association between DNA strand breaks in peripheral blood mononuclear cells and polyunsaturated fatty acids in red blood cells from women

Lipid peroxidation of polyunsaturated fatty acids (PUFA) generates reactive products that may cause DNA damage. To examine the possible relationship between DNA damage in peripheral blood mononuclear cells (PBMC) and the concentration of PUFA in red blood cells (RBC), endogenous DNA strand breaks, formamidopyrimidine DNA glycosylase (FPG) sites, and hydrogen peroxide (H2O2) sensitive sites were evaluated by the comet assay in blood samples from 98 Icelandic women. Fatty acid composition of RBC was analyzed by gas chromatography. Endogenous DNA strand breaks in PBMC correlated positively with the concentration of total PUFA, total n-3 PUFA, docosahexaenoic acid, linoleic acid, oleic acid, and palmitic acid in RBC. However, there was no association between FPG sites or H(2)O(2) sensitive sites in DNA in PBMC and the concentration of total PUFA or total saturated fatty acid in RBC. As there was no association between oxidative DNA damage or sensitivity of DNA to oxidative stress and the concentration of PUFA in RBC, the positive association between endogenous DNA strand breaks in PBMC and the concentration of total PUFA in RBC is probably not related to oxidative stress.     

Sensitivity of BRCA2 mutated human cell lines to Aurora kinase inhibition

Aurora kinases play a vital part in successful mitosis and cell division. Aberrant Aurora-A and -B expression is commonly seen in various types of tumors. Small molecule Aurora inhibitors have already entered clinical trials. Aurora-A amplification has been shown to be associated with breast tumors from BRCA2-mutation carriers and such patients might therefore be candidates for treatment with Aurora kinase inhibitors. There is a need to identify markers that can predict sensitivity to Aurora inhibition. In this study sensitivity to the inhibitor ZM447439 was tested on a panel of 15 non-malignant and malignant epithelial cell lines that differed with respect to BRCA2 and p53 status and related to level of Aurora kinase expression. The IC₅₀ value for cell survival ranged from 1.9–8.1 μM and was not related to presence or absence of BRCA2 mutation. The levels of Aurora-A and -B expression correlated with each other but sensitivity towards ZM447439 did not correlate with levels of Aurora-A and -B mRNA expression, alone. Cells treated with the Aurora kinase inhibitor completed mitosis but cytokinesis was inhibited resulting in polyploidy and multinucleation. Different levels of polyploidy could not be fully explained by defects in p53. Only cell lines with a combination of high Aurora-A and -B expression, BRCA2 mutation and p53 defects showed more sensitivity towards Aurora inhibition than other cell lines. In conclusion, BRCA2-mutated cells showed variable sensitivity towards Aurora kinase inhibition. The level of sensitivity could not be predicted by Aurora expression levels alone but BRCA2 mutated tumors with high Aurora expression and non-functional p53 are likely candidates for treatment with Aurora inhibitors.     

Comparison of women's diet assessed by FFQs and 24-hour recalls with and without underreporters: associations with biomarkers

BACKGROUND/AIMS: Women's diet can be especially difficult to assess, as women tend to underreport their intakes more often than men and are more likely to do so if they think they are overweight or obese. The aim was to compare two methods to assess women's diet and how well they associate with biomarkers. The influence and frequency of underreporting was also investigated. METHODS: Diet of 53 women was assessed by two 24-hour recalls and a food frequency questionnaire (FFQ). Blood was analyzed for retinol, beta-carotene, vitamin C and serum ferritin, and 24-hour urine for nitrogen, potassium and sodium. Underreporting was evaluated with nitrogen excretion vs. intake, and energy intake vs. basal metabolic rate. RESULTS: Energy percent (E%) from macronutrients was similar from FFQ and 24-hour recalls, but total intake was higher from 24-hour recalls (9,516 +/- 2,080 vs. 8,183 +/- 2,893 kJ, p < 0.01). Intakes of vitamin C and potassium from both methods correlated with their respective biomarkers (r = 0.316-0.393). Underreporters had higher body mass index (BMI) than others (27.7 +/- 5.5 vs. 23.8 +/- 3.7 kg/m2, p < 0.05). They reported lower E% total fat (32 +/- 5 vs. 38 +/- 6 E%, p < 0.01) and higher E% carbohydrate (49 +/- 4 vs. 45 +/- 7 E%, p < 0.05). Correlation between intake and biomarkers increased after exclusion of underreporters. CONCLUSION: For women, FFQ and 24-hour recalls give similar E% and most nutrients correlate, but FFQ gives lower intake. Underreporters have higher BMI and diminish the correlation between calculated intake and biomarkers. This has to be considered when intake data are associated with weight management, disease and lifestyle factors.     

Relationship between high consumption of marine fatty acids in early pregnancy and hypertensive disorders in pregnancy

OBJECTIVE: To investigate whether there is a relationship between maternal intake of cod-liver oil in early and late pregnancy and hypertensive disorders in pregnancy. DESIGN: An observational prospective study. SETTING: Free-living conditions in a community with traditional fish and cod-liver oil consumption. POPULATION: Four hundred and eighty-eight low-risk pregnant Icelandic women. METHODS: Maternal use of cod-liver oil, foods and other supplements was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out twice, between 11 and 15 weeks of gestation and between 34 and 37 weeks of gestation. Supplements related to hypertensive disorders in pregnancy, i.e. gestational hypertension and pre-eclampsia, were presented, with logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, cod-liver oil and multivitamins. RESULTS: The odds ratio for developing hypertensive disorders in pregnancy for women consuming liquid cod-liver oil was 4.7 (95% CI 1.8-12.6, P= 0.002), after adjusting for confounding factors. By dividing the amount of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) into centiles, the odds ratio for hypertensive disorders across groups for n-3 LCPUFA suggested a u-shaped curve (P = 0.008). Similar results were found for gestational hypertension alone. Further, the use of multivitamin supplements without vitamins A and D in late pregnancy doubled the odds of hypertensive disorders (OR 2.4, 95% CI 1.0-5.4, P= 0.044). CONCLUSIONS: Consumption of high doses of n-3 LCPUFA in early pregnancy, or other nutrients found in liquid cod-liver oil, may increase the risk of developing hypertensive disorders in pregnancy.     

Testicular germ cell tumours in Iceland: a nationwide clinicopathological study

The purpose of this study was to examine the pathology of all germ cell tumours of the testis diagnosed in Iceland 1955-2002. A total of 214 patients were included in the study. The current age-standardized incidence was found to be 6.1 per 100,000 and had increased almost fourfold during the study period. Seminoma was diagnosed in 55% of cases. Non-seminomas were diagnosed in 45%, and these were further classified as mixed germ cell tumours (33%), embryonal carcinoma (8%), teratoma (3%), and yolk sac tumour (n=1). The mean age at diagnosis was significantly higher for the seminomas than the non-seminomas (38 years versus 29 years) (p<0.001) and the non-seminomas were diagnosed at a significantly higher stage than the seminomas (p<0.001). Thus, in seminoma patients the tumour was localized to the testis (stage I) in 81% of cases, in 17% of patients the tumour had spread to the lymph nodes (stage II or III), and only 2% had extranodal metastasis at diagnosis (stage IV). In contrast, in the non-seminoma patients, the tumours were found to be stage I in 56%, stage II or III in 24%, and stage IV in 20% of cases. No significant difference in staging was found between non-seminoma subtypes. Identification of necrosis or vascular invasion was significantly associated with metastatic disease at diagnosis (p=0.002). During the study period a significant increase in stage I tumours was found as well as a decrease in the size of the tumours.     

Late and very late mortality in 5-year survivors of childhood cancer: changing pattern over four decades--experience from the Nordic countries

Long-term survivors of childhood cancer suffer from a higher mortality than the general population. Here we evaluate late and very late mortality, and patterns of causes of death, in 5-year survivors after childhood and adolescent cancer in cases diagnosed during four decades in the five Nordic countries. The study is population-based and uses data of the nationwide cancer registries and the cause of death registers. There were in all 37,515 incident cases, diagnosed with cancer before the age of 20 years, between 1960 and 1999. The 5-year survivor cohort used in the mortality analyses consisted of 21,984 patients who were followed up for vital status until December 31, 2005 (Norway, Sweden) or 2006 (Denmark, Finland, Iceland). At the latest follow-up, 2,324 patients were dead. The overall standardized mortality ratio was 8.3 and the absolute excess risk was 6.2 per 1,000 person-years. The pattern of causes of death varied markedly between different groups of primary cancer diagnosis, and was highly dependent on time passed since diagnosis. With shorter follow-up the mortality was mainly due to primary cancer, while with longer follow-up, mortality due to second cancer and noncancer causes became more prominent. Mortality between 5 and 10 years after diagnosis continued to decrease in patients treated during the most recent period of time, 1990-1999, compared to previous periods, while mortality after 10 years changed very little with time period. We conclude that improvement of definite survival demands not only reducing early but also late and very late mortality.     

Differences in survival from prostate cancer in Denmark,Iceland and Sweden

IntroductionRegister-based studies have shown large survival differences among prostate cancer patients in the Nordic countries. The aim of this study was to determine the background of such differences in Denmark, Iceland and Sweden.Material and methodsPatients with prostate cancer were identified through population-based cancer registers in the three countries. Clinical findings at diagnosis were retrieved from hospital records. In Sweden, clinical information was gathered from regional population-based prostate cancer registers. Country-specific incidence and excess mortality rates were compared, with adjustment for prognostic factors.ResultsThe relative survival in the cohorts was comparable to that in previous population-based studies. Significant differences in excess mortality rates were found across countries, which diminished or disappeared after adjustment for patient characteristics, i.e. metastatic status, clinical T stage and prostate-specific antigen level. A difference in the proportion of patients with metastatic disease was the main explanation of the differences in survival among countries, while the incidence rates of metastatic cancer were similar.DiscussionRegister-based studies of the relative survival of prostate cancer patients are influenced by national differences in clinical presentation at diagnosis. Differences in the proportion of patients with metastatic spread explained most of the difference in relative survival among patients in Denmark, Iceland and Sweden. Future country comparisons of relative survival should include adjustment for differences in patient characteristics, such as stage, prostate-specific antigen level and screening intensity.