Reproductive factors and breast cancer risk in Iceland. A second cohort study

In a previous prospective study we showed elevated risks for breast cancer in nulliparous women compared to parous women, in those having their first pregnancy at a higher age, and those with few children. This was based on 216 women diagnosed with breast cancer during 1965 to 1975 among 34,525 women having attended the cervix cancer detection clinic in Iceland by the end of 1974, and born between 1906 and 1945. The present investigation on 848 cases, diagnosed among 6 1,040 women attending the cervix cancer detection clinic during 1964 to 1984 and born between 1901 and 1960, shows the same risk factors to be significant. The relative risks are, however, smaller. The reasons for the difference in relative risks are discussed, We find that the effect of age at first birth is significant for women up to the age of 65 and not for older women. In both cohorts, women older than 55 are underrepresented and more so in the earlier report. In addition, the small number of cases in the reference group with age at first birth below 20 appears to have made the figures of our earlier report unreliable.     

Transgenic mouse models of breast cancer

Summary Although valuable initial information can be gathered about transformation fromin vitro studies, human cancer occurs in the context of a complex interaction with its environment and must ultimately be studied in living animals. Transgenic animal models have been used to study breast transformation for a number of years and have yielded valuable information on the subject. In this paper, we will summarize results from our laboratories, and others, regarding the use of transgenic mice to study breast tumorigenesis. We will also suggest future directions for the use of transgenic models to understand, and hopefully, one day to cure the disease. Note: genes are referred to as lowercase names in italics (e.g.myc) and their protein products as uppercase (e.g. Myc).     

Minerals and trace elements in Icelandic dairy products and meat

The aim of this study was to update the Icelandic Food Composition Database with respect to minerals (Ca, K, Mg, Na, and P) and trace elements (Cu, Fe, Hg, Se, and Zn) in frequently consumed agricultural products and to study the seasonal and geographical variation for these elements. Five food products typical for the Icelandic food basket were analysed: whole milk, fresh cheese (skyr), firm cheese (Gouda), lamb meat and minced beef together with skimmed milk, cream and whey. Concentrations of minerals and trace elements were determined by an inductively coupled plasma mass spectrometer (ICP-MS). Seasonal and geographical variation in whole milk was found only for selenium. Concentration of selenium in meat was variable and especially low for beef (1.4–9.6 μg/100 g fresh weight). Mercury was below the detection limit of 0.3 μg/100 g except for one sample of cheese. Skyr was rich in protein, calcium and phosphorus and retains almost all selenium in the skimmed milk used for its production. Skyr whey contains more calcium, magnesium, phosphorus and zinc than cheese whey. Skyr whey is a nutritious product, almost as rich in calcium, potassium and zinc as whole milk and could be used more by the Icelandic food industry.     

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).     

Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population‐based case–control study in four Nordic countries

The aim of this study was to assess the effect of occupational solvent exposure on the risk of adult chronic lymphocytic leukemia (CLL). The current case–control study was nested in the Nordic Occupational Cancer Study (NOCCA) cohort. 20,615 CLL cases diagnosed in 1961–2005 in Finland, Iceland, Norway, and Sweden, and 103,075 population‐based controls matched by year of birth, sex, and country were included. Occupational histories for cases and controls were obtained from census records in 1960, 1970, 1980/1981, and 1990. Exposure to selected solvents was estimated by using the NOCCA job‐exposure matrix (NOCCA‐JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Overall, nonsignificant CLL risk elevations were observed for methylene chloride, perchloroethylene, and 1,1,1‐trichloroethane. Compared to unexposed, significantly increased risks were observed for cumulative perchloroethylene exposure ≤13.3 ppm‐years (OR = 1.85, 95% CI 1.16–2.96) and average life‐time perchloroethylene exposure ≤2.5 ppm (1.61, 95% CI 1.01–2.56) among women, and cumulative methylene chloride exposure ≤12.5 ppm‐years (OR = 1.19, 95% CI 1.01–1.41) and 12.5–74.8 ppm‐years (OR = 1.23, 95% CI 1.01–1.51) among men in an analysis with 5 years lag‐time, though without dose–response pattern. Decreased CLL risk was observed for aliphatic and alicyclic hydrocarbon solvents and toluene. This study did not support associations for solvent exposure and CLL. Observed weak associations for methylene chloride, perchloroethylene, 1,1,1‐trichloroethane exposures, aliphatic and alicyclic hydrocarbons and toluene were not consistent across sexes, and showed no gradient with amount of exposure.     

Adenocarcinoma of the prostate in Iceland: a population-based study of stage, Gleason grade, treatment and long-term survival in males diagnosed between 1983 and 1987

OBJECTIVE: To investigate adenocarcinoma of the prostate in a single population with an extended follow-up period. MATERIAL AND METHODS: Using the Icelandic Cancer Registry, we identified all Icelandic men diagnosed with prostate cancer between 1983 and 1987. Disease stage, initial treatment and follow-up information were obtained from hospital records and death certificates. A critical evaluation was made of the accuracy of the death certificates regarding prostate cancer. All available histology information was reviewed and graded according to the Gleason grading system. RESULTS: A total of 414 men were diagnosed with adenocarcinoma of the prostate. Of these, 370 were alive at the time of diagnosis and stage could be determined. Four stage groups were defined: focal incidental (n=50); localized (n=164); local advanced (n=32); and metastatic disease (n=124). The mean age at diagnosis was 74.4 years (range 53-94 years). The combined Gleason score was 2-5 in 89, 6-7 in 117, 8-10 in 117 and unknown in 47 cases. The median follow-up period for the group was 6.15 years (range 0.3-19.8 years). Thirty men received treatment with curative intent: radiation therapy, n=20; and radical prostatectomy, n=10. A total of 334 patients died during the follow-up period, of whom 168 (50%) died of prostate cancer. Prostate cancer-specific survival at 10 and 15 years was 100% and 90.6%, respectively for focal incidental cancer; 73.1% and 60.8% for men with localized disease; 23.4% and 11.7% for local advanced disease; and 6.81% and 5.45% for metastatic disease. A Cox multivariate analysis showed age, stage and Gleason score to be independent predictors of prostate cancer death. A total of 104 patients with localized disease and a Gleason score of 相似文献   

Familial risk of prostate cancer in Iceland

OBJECTIVE: To estimate the risk of prostate and other types of cancer among relatives of Icelandic men diagnosed with prostate cancer over a 5-year period. PATIENTS AND METHODS: The risk ratio (RR) was used to estimate the risk among relatives of 371 patients with prostate cancer, all of whom lived in Iceland and were diagnosed when alive over a 5-year interval (1983-7). Information on cancer incidence was obtained from the population-based Icelandic Cancer Registry, and information on families from a comprehensive genealogical database covering the population of Iceland. RESULTS: First-degree male relatives were at a 1.7-fold greater age-adjusted risk of prostate cancer (1832 men; 95% confidence interval, CI, 1.28-2.34). The risk was independent of proband's age at diagnosis. First-degree male relatives of patients who died from prostate cancer were at a statistically significantly greater risk of the disease (784 men; RR 2.17; 95% CI 1.34-3.53) and relatives of patients with incidental disease (T1a) were at a greater risk but not statistically significant so (261; RR 1.86; 95% CI 0.75-4.58). Female first-degree relatives were not at greater risk of breast cancer. The risk of kidney cancer was higher in first- and second-degree female relatives, with an RR (n, CI) of 2.50 (1780, 1.10-5.66) and 2.67 (5534, 1.04-6.81), respectively. The risk of kidney cancer was not statistically significantly greater in male relatives. CONCLUSION: Family history is a risk factor for prostate cancer in Icelandic men. The risk is potentially higher for relatives of patients who die from the disease. Female relatives are not at greater risk of breast cancer but they may be at greater risk of kidney cancer.