Rofecoxib, but not celecoxib, increases the risk of thromboembolic cardiovascular events in young adults-a nationwide registry-based study.

PURPOSE: To examine the risk of thromboembolic cardiovascular events in users of coxibs and NSAIDs in a nationwide cohort. METHODS: Data were synchronised from three nationwide databases, the Icelandic Medicines Registry (IMR), The Icelandic National Patient Registry (INPR) and the Registry for Causes of Death at Statistics Iceland (RCD), for prescriptions for NSAIDs or coxibs with respect to hospitalisation for unstable angina pectoris, myocardial infarction and cerebral infarction over a 3-year period. The Cox proportional hazards model and Poisson regression were used to analyse the data. RESULTS: A total of 108,700 individuals received prescriptions for NSAIDs or coxibs (ATC code M01A), of whom 78,539 received one drug only (163,406 person-years). Among those receiving only one drug 426 individuals were discharged from hospital with endpoint diagnoses. In comparison to diclofenac, the incidence ratios, adjusted for age and gender, were significantly higher for cerebral infarction (2.13; 95% CI 1.54-2.97; P < 0.001), for myocardial infarction (1.77; 95% CI 1.34-2.32; P < 0.001) and for unstable angina pectoris (1.52; 95% CI 1.01-2.30; P = 0.047) for patients who used rofecoxib. For naproxen users, the incidence ratio was 1.46 for myocardial infarction (95% CI 1.03-2.07; P = 0.03), but was reduced in ibuprofen users (0.63; 95% CI 0.40-1.00; P = 0.05). The youngest users of rofecoxib (< or =39 years) had the highest hazard ratio (HR) for cardiovascular events (8.34; P < 0.001), while those > or =60 years had a lower but still significantly elevated HR (1.35; P = 0.001). CONCLUSION: This Icelandic nationwide registry-based study amounting to 163,406 patient-years showed increased risk of cardiovascular events, i.e. cerebral infarction, myocardial infarction and unstable angina pectoris, among rofecoxib and naproxen users in comparison to diclofenac users. The added risk was most pronounced in young adults using rofecoxib.

The efficacy of HPV 16/18 vaccines on sexually active 18-23 year old women and the impact of HPV vaccination on organized cervical cancer screening.

OBJECTIVE: Evaluate the efficacy of catch-up HPV vaccination in sexually active young women and the potential impact of HPV vaccines on the practice of organized screening. SAMPLE: (1) Women enrolled in the Future II study and (2) from a separate population-based study in Iceland. METHODS: (1) Analysis of cytological and histological results and colposcopic examinations among 710 women, aged 18-23, with less than five sexual partners, irrespectively of baseline HPV status at enrolment. (2) The impact on screening practice as determined by evaluating the distribution of 12 oncogenic HPV types in 582 cervical intraepithelial lesions (CIN 2-3) and cancer cases. MAIN OUTCOME MEASURES: (1) Distribution of evaluated parameters according to age at enrolment. (2) Age distribution of four HPV groups, within age classes and HPV groups: mean time to development of lesions, mean time to development of CIN 2-3+, cumulative frequency for CIN 2-3+ lesions after the last normal smear. RESULTS: (1) After an average 52 months of post-enrolment follow-up, significant reductions in all evaluated parameters were observed in women aged 18-19 at enrolment. (2) Among women <25 years, the proportion of cases with only HPV 16/18 was significantly lower and the proportion containing HPV16/18 plus > or =1 out of 10 non-vaccine HPV types (31/33/45/52/58/35/39/51/56/59) was higher than at age 25-49. The proportion of cases containing only the non-vaccine types was the same within all age groups. Cases with HPV 16/18 and some non-vaccine types decreased significantly with age and accumulated more slowly after the last negative smear. CONCLUSIONS: Catch-up vaccination of younger women should be considered in the context of sexual practices and the effects of prevalent disease on observed vaccine efficacy. Current data do not support a change in the lower age limit or screening intervals for women.

HPV genotypes in CIN 2-3 lesions and cervical cancer: a population-based study.

The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.

Is it rational to start population-based cervical cancer screening at or soon after age 20? Analysis of time trends in preinvasive and invasive diseases.

The effect of starting screening at age 20 in 1988 was assessed by analysing (a) the age-specific incidence and distribution of stage and histology of invasive diseases, and (b) the detection rates of histologic moderate to high-grade intraepithelial neoplasia (CIN 2-3/AIS), and 1st abnormal cytology and repeat low-grade cytology after follow-up observation. Cancer incidence increased significantly at age 25-34 after 1979 due to early stage squamous cell and adenocarcinoma. After an initial increased rate of preinvasive disease, CIN 3 decreased significantly at age 30-34 after 1988, at age 25-29 after 1993, and levelled out after 1998 at age 20-24. The rates of CIN 2 levelled out after 1998. The rates of repeat low-grade smears decreased after observation at age 20-24 by 80%. The study confirms an increasing rate of preinvasive and invasive disease among younger women and indicates the benefit of starting organised screening at 2-3 year intervals soon after age 20.

Epidemiology of kidney stones in Iceland: a population-based study.

OBJECTIVE: The prevalence of kidney stones varies greatly between ethnic groups and geographic locations, ranging from 8% to 19% in males and from 3% to 5% in females in Western countries. The aim of this study was to examine the epidemiology of kidney stones in Iceland. MATERIAL AND METHODS: Data were derived from the Reykjavik Study, a population-based cohort study carried out between 1967 and 1991. All subjects answered a thorough questionnaire concerning their medical history at each visit. The lifetime prevalence of kidney stones was calculated based on the answer to the question "Have you ever been diagnosed with a kidney stone?" at each person's first visit. Incidence was calculated based on answers from subjects who had made two or more visits. Prevalence and incidence were age-standardized to the truncated world population. Family history of kidney stones was also evaluated. RESULTS: A total of 9039 men aged 33-80 years and 9619 women aged 33-81 years participated. Of these, 423 males and 307 females had a history of kidney stones (p=0.001). Prevalence increased significantly with age for both genders. Men aged 30-34 years had a prevalence of 2.9%, compared to 8.8% for those aged 65-69 years, whereas corresponding values for women were 2.5% and 5.0%. The age-standardized prevalence for the 30-79 years age group was 4.3% for men and 3.0% for women. No significant increase in prevalence was observed over time. The incidence was 562 per 100 000 per year among men and increased significantly with age. The incidence among women was 197 per 100 000 per year and did not differ between age groups. A family history of nephrolithiasis was present in 25% of subjects with a history of kidney stones, and in 4% of those without. CONCLUSIONS: The incidence and prevalence of kidney stones in Icelandic women are similar to those that have been reported in other Western countries. The prevalence among men is lower that in neighboring countries but the incidence is similar. A strong family history of kidney stones suggests a genetic predisposition.

Effectiveness of cervical cancer screening in Iceland, 1964-2002: a study on trends in incidence and mortality and the effect of risk factors.

BACKGROUND: Data on cervical cancer screening programs that have covered a whole nation over a prolonged time are scarce. The effectiveness of a 40-year established nationwide cervical screening program has been evaluated to define optimal age limits and screening intervals. METHODS: Trends in incidence and mortality by calendar time, age, histology, stage and attendance during 1964-2002 and the predictive power of calendar year, age, stage and histology on the cause-specific mortality rate were analyzed. RESULTS: The rate of squamous cell carcinoma decreased significantly, but the rate of adenocarcinoma increased. The age-specific incidence and cause-specific mortality decreased significantly for all age groups except those women aged 20-29 years. An increased age-specific incidence rate, confined to stage I, was observed in the age group 20-39 years after 1980 and a positive correlation was observed between early attendance and the rate of microinvasive squamous (stage IA) cell carcinoma and adenocarcinoma in this age group. The cumulative incidence of invasive disease started to increase two years after the last negative smear. Stage was the strongest risk factor, followed by age and calendar time, and to a lesser degree histology. CONCLUSIONS: The results confirm the effectiveness of the screening program and support the recommendation that screening should commence below age 25 with a maximum of 3-year initial screening intervals. The interval can then be extended after age 40 and stopped after age 65.

Longitudinal trends in cervical cytological lesions and the effect of risk factors. A 30-year overview.

BACKGROUND: Cytological preinvasive changes are important precursors in cervical cancer, therefore variations in their trends affect screening guidelines. METHODS: Trends in cytological preinvasive changes following the 1st to 5th screening visits in the 20-34 and 35-69 year age groups were analyzed for the period 1979-2002: a) the incidence rate (absolute risk) of higher grade cytology and the relative risk of risk factors on this rate; b) the cumulative incidence of low-grade and higher grade smears after normal and abnormal screening results; c) the cumulative incidence of higher grade cytology at a fixed risk level after normal screening results; and d) the prevalence of higher grade smears at first screening visit in the 20-24/25-29 year age groups during 1971-2002. RESULTS: An increased trend in the prevalence of higher-grade smears was observed at the first screening visit after 1980. The main risk variables for higher-grade smears in both age groups were low-grade changes and inflammation followed in the younger age group by calendar year. However, age correlated with a decreased risk ratio. After normal screening the cumulative incidence rate of low and higher-grade smears increased almost linearly with time. The screening interval before diagnosis of higher-grade smears increased with both age and number of normal visits, but leveled out after the age of 35-40. CONCLUSIONS: Trends in higher-grade smears indicate that screening should preferably start before age 25 with a maximum interval of 3 years. The interval can be extended after age 35-40. Low-grade smears or inflammation need closer follow-up.

Longitudinal trends in cervical histological lesions (CIN 2-3+): a 25-year overview.

BACKGROUND: Trends in CIN 2-3+ lesions affect the choice of target age group and screening interval. METHODS: The following analyses were performed for CIN 2-3+ following 1st to 5th screening visits in the 20-34/35-69 age groups during 1979-2002: a) the relative risk of age and calendar year; b) the cumulative incidence rate after normal or low or higher grade cytology; c) the proper screening interval to detect these lesions at a fixed risk level after normal screening visits; d) the predictive power of these lesions for diagnosis of cancer after first biopsy; e) the prevalence rates in the 20-24/25-29 year age groups at first and at all subsequent screening visits. RESULTS: The cumulative rate decreased with the number of screening visits and advancing age. After normal and low-grade cytology the cumulative rate increased linearly but slowly with time but after higher grade cytology the rate was relatively stable within one year. Age and calendar year are important risk factors in younger women. The prevalence of CIN 2-3+ increased significantly at 1st visit in the 20-24 age group at the same time as the population prevalence in the 25-29 age group decreased significantly. CIN 2 was at lower risk than CIN 3 of being diagnosed with cancer. CONCLUSIONS: The results indicate that screening should preferably start before age 25 with a maximum interval of 3 years, whereas the interval can be extended to 4-5 years at age 35-40. CIN 2 have a different risk profile compared to CIN 3.

Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000.

BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5. METHODS: Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided. RESULTS: Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out. CONCLUSIONS: The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.

[Coronary risk factors among men and women in Iceland. Results from the Reykjavik Study 1967-1985. 1992]. / Ahaettuthaettir kransaedasjúkdóms medal karla og kvenna á Islandi. Nidurstödur úr hóprannsókn Hjartaverndar 1967-1985.

The Reykjavík Study 1967-1985: Risk factors for coronary heart disease mortality have been investigated in a prospective study of 8001 randomly selected Icelandic men and 8468 women. The men were aged 34-64 and the women 34-76 at the time of their first examination. After followup from 2-17 years 1140 (14.2%) of the men and 537 (6.3%) of the women had died. Coronary heart disease accounted for 43% of the mortality among the men, cancer 27% and cerebrovascular disease 7%. This distribution is in contrast to what was found among the women. Coronary heart disease accounted for 19.4% of the mortality, cancer 42.3% while the relative contribution of cerebrovascular mortality was similar. The effects of various factors were assessed simultaneously with multivariate survival analysis using the Cox's proportional hazard model. Age, serum total cholesterol, triglycerides, smoking and systolic blood pressure were all significant independent risk factors for coronary heart disease mortality in both sexes. Fasting blood sugar was of borderline significance, reaching significance among men, but not among women. However, since the women have much lower risk of dying from coronary heart disease than the men the absolute risk associated with each of the risk factors is much lower in the women.

Hypertension control as predictor of mortality in treated men and women, followed for up to 30 years.

PURPOSE: To examine the prognosis of treated, hypertensive individuals in the Reykjavik Study. METHODS: A population-based longitudinal study of 9328 men and 10 062 women. Subjects were included in the study during the period 1967-1996. Two groups of treated, hypertensive subjects were defined at baseline: with controlled blood pressure and with uncontrolled blood pressure. Main outcome measures were cardiovascular disease (CVD) mortality and all-cause mortality. RESULTS: Of the hypertensive men 24.8% were treated, and of those 38.3% were controlled, and of the hypertensive women 45.3% were treated, and of those 52.7% were controlled. Comparing treated and uncontrolled (systolic blood pressure (SBP) > or =160 mmHg and/or diastolic blood pressure (DBP) > or =95 mmHg) versus treated and controlled hypertensive subjects, followed for up to 30 years, the uncontrolled men and women were at significantly higher risk of CVD mortality, hazard ratio (HR) = 1.47 (95% confidence interval (CI): 1.06-2.02) and HR 1.70 (CI: 1.23-2.36), respectively, showing the benefit of hypertension control. The risk of all-cause mortality was increased for treated, uncontrolled men and women, compared with those who were treated and controlled, but did not reach significance. When analyzing blood pressure as a continuous variable among treated, hypertensive subjects, SBP was a better predictor than DBP of CVD mortality and all-cause mortality in women. This was not the case in men. CONCLUSIONS: Control of blood pressure among hypertensive-treated subjects at baseline was associated with a lower risk of CVD mortality during follow-up. SBP was the single best predictor of CVD mortality and all-cause mortality in treated women. The uncontrolled women were at a higher risk than the uncontrolled men.

Risk factors for out-of-hospital cardiac arrest: the Reykjavik Study.

AIMS: To examine risk factors for out-of-hospital cardiac arrest in the Reykjavik Study, a long-term, prospective, population-based cohort study that started in 1967. METHODS AND RESULTS: From 1987 to 1996, 137 men and 44 women out of the 8006 men and 9435 women in the study sustained out-of-hospital cardiac arrest due to cardiac causes. Determinants included coronary artery disease (CAD), its classical risk factors, and age, body mass index (BMI), heart rate, cardiomegaly, and erythrocyte sedimentation rate. Electrocardiograms (ECGs) were examined for various abnormalities. Significance was determined by Cox regression analysis. In multivariable analysis, the risk in men was significantly associated with age, diastolic blood pressure, cholesterol, current smoking, and previous diagnosis of myocardial infarction (MI). In women, the risk was associated with diastolic blood pressure, elevated levels of cholesterol and triglycerides, and increased voltage on ECG. Increased BMI was inversely related to women's risk of out-of-hospital cardiac arrest. CONCLUSION: In this prospective, population-based cohort study previous MI and the classical risk factors for CAD significantly increased the risk of out-of-hospital cardiac arrest, the endpoint of this study. Increased voltage on ECG additionally increased women's risk.

Familiality of benign and malignant paraproteinemias. A population-based cancer-registry study of multiple myeloma families.

BACKGROUND AND OBJECTIVES: The occurrence of two or more cases of multiple myeloma (MM) in the same family has been reported from time to time. The current study is the first population- and cancer-registry-based survey to investigate familiality of premalignant or malignant B-cell proliferation. DESIGN AND METHODS: A family registry of 218 multiple myeloma cases was compared with the records of the Icelandic Cancer Registry in order to analyze the pedigrees for the occurrence of families with multiple cases of paraproteinemia and hematologic malignancies. RESULTS: The relative risk of developing monoclonal gammopathies of unknown significance (MGUS) was not increased among first-degree relatives of MM patients, but there was a significantly increased risk of developing MM for females separately (RR = 3.23, CI 1.17-7.01) and for males and females combined (RR = 2.33, CI 1.12-4.26). Analysis for all hematologic malignancies showed an increased risk for female relatives of MM patients (RR = 1.95, CI 1.10-3.20). Eight families were identified in which the propositus with MM had > 1 relatives with MGUS and > 1 with another hematologic malignancy, including 4 families with another relative with MM. In three families both myeloid and lymphoid malignancies occurred. INTERPRETATION AND CONCLUSIONS: Although inheritance does not appear to be a major risk factor for the development of paraproteinemias a significant risk of developing MM was found for female relatives. The occurrence of multiple cases of benign and malignant paraproteinemias in a few families does suggest a hereditary contribution. Further studies of such families might reveal clues on pathogenesis.

Fracture rate in a population-based sample of men in Reykjavik.

The population-based Reykjavik Heart Study, started in 1967, aims at finding and evaluating risk factors for cardiovascular diseases. It included 4,137 men born between 1907 and 1934 and we examined all fractures recorded in these subjects from January 1977 until the end of December 2000, or death. Their mean age at the start of this study was 54 (42-69) years and the mean follow-up time 19 years. We examined the patients' records, including those from the Radiological Departments in all Reykjavik hospitals and the only out-patient accident clinic in Reykjavik. Old fractures and those caused by a malignancy were excluded. The intensity of the trauma was estimated from E-numbers. Altogether 1,531 fractures were recorded in 939 (23%) persons. A low-energy trauma caused 53% of all fractures. 612 had a single fracture during this period. 323 had two or more fractures--a 53% risk of sustaining additional fractures. The fracture incidence increased by 40% in each 10-year period. Fractures of the ribs were commonest (246), followed by those of the hand (241). 135 were hip fractures, 75% caused by low-energy trauma. The fracture rate was 20 per 1000 persons year--i.e., similar to that in other studies.

The absolute risk of recurrent myocardial infarction is similar amongst both sexes: MONICA Iceland Study 1981-1999.

BACKGROUND: To do a gender comparison of absolute risk of recurrent myocardial infarction (MI). DESIGN: Registration of all first and second MI amongst Icelandic males and females 1981-1999. METHODS: The whole of Icelandic population, 40-74 years of age. RESULTS: The mean recurrence rate (second attack) for men was 45.7/1000 MI survivors/year and for women 39.0/1000 per year. The male/female (M/F) ratio was 1.17, 95% confidence interval 1.00-1.37, P = 0.05 and did not change significantly with age. The M/F ratio for first MI in comparison was two to seven, lowest in the oldest group. The recurrence rate decreased significantly and similarly in both sexes during the observation period. CONCLUSION: The absolute risk of MI is closely similar amongst both sexes and has decreased similarly suggesting that the same kind of secondary intervention is effective amongst both sexes in a general population.

Erythrocyte sedimentation rate, an independent predictor of coronary heart disease in men and women: The Reykjavik Study.

The relation between erythrocyte sedimentation rate (ESR) and risk of developing coronary heart disease (CHD) or fatal cerebrovascular accident was assessed in a cohort of 7,988 men and 8,685 women who participated in The Reykjavik Study (Iceland). Cardiovascular risk assessment was based on characteristics at baseline, from 1967 to 1996. During an average follow-up of 19 and 20 years, 2,092 men and 801 women, respectively, developed CHD, and 251 men and 178 women died from cerebrovascular accident. For men, the fully adjusted increase in risk of developing CHD predicted by the top compared with the bottom quintile of ESR was 57% (hazard ratio = 1.57, 95% confidence interval: 1.38, 1.78; p < 0.001); for women, risk was increased by 49% (hazard ratio = 1.49, 95% confidence interval: 1.16, 1.90; p < 0.001). The increased risk after baseline ESR measurement was stable for up to 25 years for men and 20 years for women. The fully adjusted risk of death due to stroke predicted by increasing the ln(ESR + 1) by one standard deviation was increased by 15% for men (p = 0.06) and 16% for women (p = 0.08). In conclusion, ESR is a long-term independent predictor of CHD in both men and women. These findings support the evidence of an inflammatory process in atherosclerosis.

Prediction of cancer incidence in the Nordic countries: empirical comparison of different approaches.

Prediction of the future number of cancer cases is of great interest to society. The classical approach is to use the age-period-cohort model for making cancer incidence predictions. We made an empirical comparison of different versions of this model, using data from cancer registries in the Nordic countries for the period 1958-1997. We have applied 15 different methods to 20 sites for each sex in Denmark, Finland, Norway and Sweden. Median absolute value of the relative difference between observed and predicted numbers of cases for these 160 combinations of site, sex and country was calculated. The medians varied between 10.4 per cent and 15.3 per cent in predictions 10 years ahead, and between 15.1 per cent and 32.0 per cent for 20 year predictions. We have four main conclusions: (i) projecting current trends worked better than assuming that future rates are equal to present rates; (ii) the method based on the multiplicative APC model often overestimated the number of cancer cases due to its exponential growth over time, but using a power function to level off this growth improved the predictions; (iii) projecting only half of the trend after the first 10 years also gave better long-term predictions; (iv) methods that emphasize trends in the last decade seem to perform better than those that include earlier time trends.

[Changes in smoking habits in the last thirty years in middle-aged Icelanders and their causes - Results from population surveys of the Icelandic Heart Association.].

OBJECTIVE: During the last thirty years the Research Clinic of the Icelandic Heart Association has been engaged in several extensive cardiovascular population surveys. Smoking habits have been assessed by a questionnaire and the purpose of the present study is to describe the changes in smoking habits during the period 1967-2001, their causes and the reliability of the information gathered. MATERIAL AND METHODS: The subjects were participants in four population surveys: The Reykjavik Study 1967-1996, Survey of "Young People" 1973-1974 and 1983-1985, MONICA Risk Factor Surveys 1983, 1988-1989 and 1993-1994 and the "Reykjavik Offspring Study" 1997-2001. The age of participants was 30-88 years and 26,311 examinations of males and 26,222 of females were performed, a number of individuals attending more often than once. A standardized smoking questionnaire was used and the reliability was assessed. RESULTS: Smoking prevalence decreased substantially in both sexes during the study period. In the youngest male group the prevalence decreased from 65% to 42%, but in the oldest from 45% to 19%, while in the youngest female group the decrease was from 50% to 35% but in the oldest age group from 30% to 20%. The decrease in smoking was almost exclusively in the category of "light smokers" (i.e. 1-14 cigarettes a day or pipe/cigar smoker). The main reasons for quitting smoking were concerns about health and symptoms associated with smoking and the cost. The cost had greater weight at the beginning of the period than during the latter part but health concerns seem to be increasingly important. Compared to other countries smoking prevalence in Icelandic males is low but high in females. CONCLUSION: During the last three decades smoking prevalence in Icelanders 30 years and older has decreased substantially. The main reasons for quitting smoking are health concerns and cost. Continued information about the deleterious effects of smoking as well as increase in the price of tobacco is likely to reduce further the smoking prevalence.

Segregation analysis of 389 Icelandic pedigrees with Breast and prostate cancer.

Breast cancer and prostate cancer are the most commonly occurring cancers in females and males, respectively. The objective of this project was to test the hypothesis that breast cancer in females and prostate cancer in males represent homologous cancers that may be controlled by one or more common unidentified genes that may explain some of the observed familial aggregation. We modeled the transmission of a breast-prostate cancer phenotype in 389 pedigrees ascertained through a breast cancer proband drawn from the Icelandic Cancer Registry. Assuming that age at diagnosis of this combined phenotype followed a logistic distribution, segregation analyses were performed to evaluate residual parental effects, a sibship covariate, and a dichotomous cohort effect. The most parsimonious model was a Mendelian codominant model, which could partly explain the familial aggregation of both cancers. Inheritance of a putative high-risk allele (A) predicted gender-specific mean ages of onset for females as 53.8 years, 59.7 years, and 65.6 years for the putative AA, AB, and BB genotypes, respectively. Similarly, the predicted means were 73.7 years, 75.6 years, and 78.3 years, respectively, among males. Under this codominant model, the lifetime risk of a woman being affected was 19% by age 80 years. This implies that when prostate cancer among male relatives of breast cancer probands (unselected for family history or early-onset disease) is considered a pleiotrophic effect of the same gene that increases the risk for breast cancer, women are predicted to have a less than 1 in 5 risk of developing breast cancer when they carry the putative high-risk allele. However, this is a higher risk than in the general Icelandic population. Our results suggest that BRCA2 mutations alone are inadequate to explain all of the excess clustering of prostate cancer cases in families of breast cancer probands, and that additional genes conferring excess risk to both breast and prostate cancer may exist in this population.

Prevalence and progression of CRF in Iceland: a population-based study.

BACKGROUND: The prevalence of end-stage renal disease (ESRD) is lower in Europe than in the United States. The purpose of this study was to examine whether this difference results from a lower prevalence or slower progression of chronic renal failure (CRF) in a European cohort. METHODS: We studied 18,912 subjects (9,773 women, 9,139 men) aged 33 to 81 years who participated in the Reykjavik Study between 1967 and 1991. Subjects with serum creatinine (SCr) levels of 1.7 mg/dL (150 micromol/L) or greater were considered to have CRF. We determined the crude prevalence of CRF, as well as age-standardized prevalence for 5-year age groups, in individuals aged 30 to 79 years. Progression of CRF was defined as a decrease in estimated glomerular filtration rate greater than 1 mL/min/1.73 m2/y. RESULTS: Of 49 individuals who had an SCr of 1.7 mg/dL (150 micromol/L) or greater at entry, 41 individuals (26 men, 15 women) had a persistent elevation in SCr levels. Thirty-four individuals had mild CRF (SCr, 1.7 to 2.8 mg/dL [150 to 250 micromol/L]), 6 individuals had moderate CRF (SCr, 2.8 to 5.6 mg/dL [250 to 500 micromol/L]), and 1 individual had ESRD. The crude prevalence of CRF was 0.22% (220/100,000); 0.15% among women and 0.28% among men. The age-standardized prevalence was 0.23% (95% confidence interval [CI], 0.04 to 0.42) for women and 0.42% (95% CI, 0.18 to 0.66) for men. Eighty-five percent of patients with CRF were 50 years or older. Twenty-seven subjects had progressive renal failure, 17 of whom progressed to ESRD during a median of 7 years (range, 3 to 21 years). CONCLUSION: The prevalence of CRF is markedly lower in Iceland than in the United States. Furthermore, 27% of subjects did not show progression of their renal failure. These factors may explain in part the difference in ESRD prevalence between European countries and the United States.