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.     

Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A

The activity of the kinase Aurora-A (Aur-A) peaks during mitosis and depends on phosphorylation by one or more unknown kinases. Mitotic phosphorylation sites were mapped by mass spec sequencing of recombinant Aur-A protein that had been activated by incubation in extracts of metaphase-arrested Xenopus eggs. Three sites were identified: serine 53 (Ser-53), threonine 295 (Thr-295), and serine 349 (Ser-349), which are equivalent to Ser-51, Thr-288, and Ser-342, respectively, in human Aur-A. To ask how phosphorylation of these residues might affect kinase activity, each was mutated to either alanine or aspartic acid, and the recombinant proteins were then tested for their ability to be activated by M phase extract. Mutation of Thr-295, which resides in the activation loop of the kinase, to either alanine or aspartic acid abolished activity. The S349A mutant had slightly reduced activity, indicating that phosphorylation is not required for activity. The S349D mutation completely blocked activation, suggesting that Ser-349 is important for either the structure or regulation of Aur-A. Finally, like human Aur-A, overexpression of Xenopus Aur-A transformed NIH 3T3 cells and led to tumors in nude mice. These results provide further evidence that Xenopus Aur-A is a functional ortholog of human Aur-A and, along with the recently described crystal structure of human Aur-A, should help in future studies of the mechanisms that regulate Aur-A activity during mitotic progression.     

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.     

BRCA2 mutation in Icelandic prostate cancer patients

 Molecular genetic analysis of prostate cancer has gained considerable attention in recent years. The hope is to find genetic markers that can help to determine which patients are likely to develop a progressive or lethal disease and would therefore benefit from early treatment. The BRCA2 gene on chromosome 13 has been associated with familial male and female breast cancer. A founder mutation in this gene has been detected in the Icelandic population. This is a 5-bp deletion that leads to an early termination and truncated protein. Clustering of prostate cancers in some of the Icelandic BRCA2 families implies that mutation carriers are at increased risk of developing cancer of the prostate. The aim of the study was to investigate this mutation in Icelandic prostate cancer patients related to BRCA2 positive breast cancer probands and to estimate the prevalence of this mutation in unselected prostate cancer patients. To examine the potential role of this mutation in prostate cancer we analyzed prostate cancer cases from 16 BRCA2 families and all available samples from individuals diagnosed with prostate cancer in Iceland over a period of 1 year. The risk ratio of prostate cancer was 4.6 (1.9–8.8) in first-degree relatives and 2.5 (1.2–4.6) in second-degree relatives of the 16 BRCA2 positive breast cancer probands. Of 26 prostate cancer cases found in these families 12 were analyzed, and 8 of these (66.7%) had the BRCA2 mutation. All of these patients developed an advanced disease, and all have died of prostate cancer (median survival 22.5 months). Among unselected cases 3.1% (2/65) had the mutation and developed an advanced disease as well. This specific mutation in the BRCA2 gene is found in a subset of Icelandic prostate cancer cases and appears to be a marker for poor prognosis. Received: 31 January 1997 / Accepted: 23 May 1997     

Genetic epidemiologic aspects of gastric cancer in Iceland

BACKGROUND: Association between gastric cancer and environmental factors (diet and infections) has been established, and genetic changes are well described in adenocarcinomas of the stomach. Less is known about clinical features of hereditary gastric cancer and whether the disease is associated with family clustering. STUDY DESIGN: Family trees of patients diagnosed with gastric cancer in Iceland between 1955 and 1999 were identified in the Genealogical Database of the University of Iceland. All probands with age of onset younger than 60 years were used in the study. Families of all probands (n = 455 men and 161 women) were traced to third degree. Through linkage of the genealogic data obtained by the Icelandic Cancer Registry (between 1955 and 1999), all reported cancers were identified in those families. The expected number of cases was calculated using age-specific population rates in Iceland. RESULTS: A relative risk (RR) of 2.2 (95% confidence interval [CI] = 1.6-3.0) and 1.3 (95% CI = 1.0-1.7) for the gastric cancer risk was observed among 2,846 first- and 8,658 second-degree relatives of male probands. For female probands the corresponding relative risks were 1.6 (95% CI = 1.1-2.6, n = 7,396) and 1.4 (95% CI = 0.9-2.0, n = 2,764). The increased risk was more pronounced for relatives of men and women diagnosed with gastric cancer before the age of 50 years. A minor difference in relative risk was found between relatives of probands who were diagnosed with intestinal type or diffuse type gastric cancer. Fifty-eight families with two or more relatives with cancer were identified. In 32 families 2 relatives with gastric cancer were identified and in 26 families 3 or more relatives had gastric cancer. CONCLUSIONS: Relatives of gastric cancer patients have two- to three-fold increased risk of developing gastric cancer. The risk is elevated for both genders.     

Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population‐based cohort study of 32,308 one‐year survivors

The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population‐based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one‐year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0–2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person‐years. At the end of follow‐up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ～500–600 per 100,000 person‐years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5–5.9), valvular dysfunction (4.6; 3.8–5.5) and cerebrovascular diseases (3.7; 3.4–4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow‐up for this rapidly growing population.     

Cancer incidence among priests: 45?years of follow-up in four Nordic countries

Previously published studies on the risk of cancer among male priests have been based on cancer mortality with the exception of one case–control study. The aim of this study was to present estimates of cancer incidence among Nordic male priests. The study cohort for our analyses consisted of 6.5 million men aged 30–64 years old who had participated in any computerised population census in four Nordic countries in 1990 or earlier. Follow-up was done by drawing linkages with the national population and cancer registries. 13,491 priests were identified by their job title codes. We estimated the standardised incidence ratio (SIR) and 95% confidence intervals (95% CI) for the priests using the male population as a reference. Priests had a lower cancer incidence than the general population (overall SIR 0.85, 95% CI: 0.82–0.88). The majority of smoking- and alcohol-related cancers were associated with decreased SIR estimates. Increased risks were observed for skin melanoma (SIR 1.34, 95% CI: 1.11–1.62), acute myeloid leukemia (SIR 1.75, 95% CI: 1.20–2.47) and thyroid cancer (SIR 1.86, 95% CI: 1.22–2.73). This is the first cohort study regarding the incidence of cancer among priests. The lower incidence of smoking and alcohol-related cancers among Nordic male priests can be explained by their lower exposure to cigarettes and alcohol when compared to the general population. A greater risk of melanoma is typical of highly-educated people, but it is unclear why priests should have an increased risk of acute myeloid leukemia or thyroid cancer.     

Vitamin D Intake and Status in 6-Year-Old Icelandic Children Followed up from Infancy

High serum 25-hydroxyvitamin D (25(OH)D) levels have been observed in infants in Nordic countries, likely due to vitamin D supplement use. Internationally, little is known about tracking vitamin D status from infancy to childhood. Following up 1-year-old infants in our national longitudinal cohort, our aims were to study vitamin D intake and status in healthy 6-year-old Icelandic children (n = 139) and to track vitamin D status from one year of age. At six years, the mean 25(OH)D level was 56.5 nmol/L (SD 17.9) and 64% of children were vitamin D sufficient (25(OH)D ≥ 50 nmol/L). A logistic regression model adjusted for gender and breastfeeding showed that higher total vitamin D intake (Odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.08–1.49), blood samples collected in summer (OR = 8.88, 95% CI = 1.83–43.23) or autumn (OR = 5.64, 95% CI = 1.16–27.32) compared to winter/spring, and 25(OH)D at age one (OR = 1.02, 95% CI = 1.002–1.04) were independently associated with vitamin D sufficiency at age six. The correlation between 25(OH)D at age one and six was 0.34 (p = 0.003). Our findings suggest that vitamin D status in infancy, current vitamin D intake and season are predictors of vitamin D status in early school age children. Our finding of vitamin D status tracking from infancy to childhood provides motivation for further studies on tracking and its clinical significance.     

Dietary patterns in adolescence and risk of colorectal cancer: a population-based study

Cancer Causes & Control - To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC). Food frequency data were obtained from the AGES-Reykjavik study,...