CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.

Genetic evidence for a family-based Scandinavian settlement of Shetland and Orkney during the Viking periods.

The Viking age witnessed the expansion of Scandinavian invaders across much of northwestern Europe. While Scandinavian settlements had an enduring cultural impact on North Atlantic populations, the nature and extent of their genetic legacy in places such as Shetland and Orkney is not clear. In order to explore this question further, we have made an extensive survey of both Y-chromosomal and mitochondrial DNA (mtDNA) variation in the North Atlantic region. Our findings indicate an overall Scandinavian ancestry of approximately 44% for Shetland and approximately 30% for Orkney, with approximately equal contributions from Scandinavian male and female subjects in both cases. This contrasts with the situation for the Western Isles, where the overall Scandinavian ancestry is less ( approximately 15%) and where there is a disproportionately high contribution from Scandinavian males. In line with previous studies, we find that Iceland exhibits both the greatest overall amount of Scandinavian ancestry (55%) and the greatest discrepancy between Scandinavian male and female components. Our results suggest that while areas close to Scandinavia, such as Orkney and Shetland, may have been settled primarily by Scandinavian family groups, lone Scandinavian males, who later established families with female subjects from the British Isles, may have been prominent in areas more distant from their homeland.

Transtheoretical model: investigation of adolescents' sunbathing behaviour.

The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden as well as in other western countries during the last 20 years. Adolescents are an important group in skin cancer prevention. Interventions targeting this group have been reported to affect knowledge and attitudes, but the effect on sun protection behaviour has been slight. The aim of this study was to investigate the applicability of the Transtheoretical Model (TTM) for skin cancer prevention for adolescents. A random sample of 1200 18-year-olds living in Stockholm County was selected from the national census registry. A questionnaire that included three of the major constructs of the TTM (i.e. stages of change, processes of change and decisional balance) was sent by mail. The majority of the teenagers were in the precontemplation stage for giving up intentional tanning. The relations between the stages of change and two other major constructs of the TTM, processes of change and decisional balance, were consistent with data on other health behaviours. The results may aid in developing successful skin cancer prevention programmes. The results give support for the stages of change measurement used in this study and that utilizing the TTM in skin cancer prevention may be appropriate.

Knowledge, attitudes and smoking behavior among Lao doctors.

The aim of this study was to describe the knowledge, attitudes and smoking behavior among doctors at Mahosot University Hospital in Lao PDR. A cross-sectional, descriptive study used a self-administered anonymous questionnaire. The study population comprised 164 doctors. Answers were retrieved from 151 (92%) of the doctors. The prevalence of smoking among male doctors was 35%, 16% smoked daily and 19% occasionally. None of the female doctors reported to have ever smoked. Out of the five diseases related to smoking, 5% of the doctors recognized all and 10% recognized only one. Doctors were significantly more likely to advise patients with symptoms related to smoking. However, approximately one in two doctors reported that they did not always counsel smokers with severe smoking related symptoms to stop smoking. Almost all doctors, independent of smoking behavior, perceived tobacco prevention to be important. The findings indicate a lack of comprehensive knowledge on tobacco related issues. Most doctors expressed a positive attitude towards tobacco prevention. An effort is needed to get doctors in Lao PDR to stop smoking engage in smoking assation support.

A reassessment of genetic diversity in Icelanders: strong evidence from multiple loci for relative homogeneity caused by genetic drift.

There has been some controversy in the literature concerning whether Icelanders are genetically homogenous or heterogeneous relative to other European populations. We reassess this question in the light of large data sets spanning 83 autosomal SNP loci, 14 serogenetic loci, 6622 Y-chromosomes and 3214 sequences from mtDNA hypervariable segments 1 and 2 (HVS1 and HVS2). Our results strongly support the hypothesis that genetic drift, with a consequent loss of variation, has had a greater impact on Icelanders than most other Europeans. We also analyse 7245 HVS1 sequences from 25 European populations. In line with other studies, we observe a deficit of rare HVS1 haplotypes and an excess of intermediate frequency haplotypes in Icelanders compared to most European populations, with some measures of genetic diversity indicating relative heterogeneity and others indicating relative homogeneity of Icelanders. Simulations indicate that genetic drift, and not admixture (as proposed by Arnason, 2003) is the most likely cause of the atypical Icelandic HVS1 frequency spectrum. These simulations reveal that gene diversity (heterozygosity) and mean pairwise differences are largely insensitive to events in recent population history, while statistics based on the number of haplotypes or segregating sites are much more sensitive. Overall, our analyses strongly indicate that the Icelandic gene pool is less heterogeneous than those of most other European populations.

'You and your skin': a short-duration presentation of skin cancer prevention for teenagers.

The effectiveness of a short-duration presentation of the educational material 'You and Your Skin' was tested on 184 adolescents (age 13-15) at the Year 7 and 8 levels. A non-equivalent control group design was used with pre-testing and post-testing 3 months after the intervention. The intervention increased the students' knowledge of known risks factors for skin cancers. However, the students' attitudes to abstaining from sunbathing and tanning was not significantly affected. The effect of the intervention on the stage of change was primarily a progression from the precontemplation stage to the contemplation stage regarding avoiding the mid-day sun. We conclude that a brief presentation of the educational kit 'You and Your Skin' can be used to increase knowledge, but there is a need for a more extensive intervention effort to affect students' readiness to change their behavior and attitude towards sunbathing and tanning. Therefore, it is important to emphasize the necessity of using the educational kit as a multi-lesson programme with its several group exercises.

The unrecognised cost of cancer patients' unrelieved symptoms:a nationwide follow-up of their surviving partners.

We investigated if a cancer patient's unrelieved symptoms during the last 3 months of life increase the risk of long-term psychological morbidity of the surviving partner. All women (n=506) living in Sweden under 80 years of age, who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were asked to answer an anonymous postal questionnaire, 2-4 years after their loss. The widows' psychological morbidity was associated with the patient's unrelieved mental symptoms. When the patient was perceived to have been very anxious during last three months of life (compared to no observed symptoms) the relative risks for the widows' psychological morbidity were: 2.5 (1.4-4.3) for depression and 3.4 (1.4-8.2) for anxiety. When comparing reports of the patient's pain (much vs no), the relative risks were 0.8 (0.5-1.2) for widowhood depression, and 0.8 (0.4-1.7) for widowhood anxiety. The patients were found to have had adequate access to physical pain control but poor access to psychological symptom control. Efficiency in diagnosing and treating psychological complications of terminally ill cancer patients may not only improve their quality of life but possibly also prevent long-term psychological morbidity of their surviving partners.

Environmental tobacco smoke exposure of young children--attitudes and health-risk awareness in the Nordic countries.

AIMS: To assess attitudes towards environmental tobacco smoke (ETS) and health-risk awareness regarding the potential hazards of ETS for children among parents of young children in the Nordic countries. Also to investigate to what extent these factors are related to ETS exposure of the children. DESIGN: A cross-sectional community-based survey using an anonymous mailed questionnaire. PARTICIPANTS: Parents of children aged 3 years at the time of selection from a random sample of 5500 households in the Nordic countries (Sweden, Norway, Denmark, Iceland and Finland). MAIN OUTCOME MEASURES: Smoking status of parents, weekly ETS exposure of children within and outside the home, health-risk awareness and attitudes regarding the potential hazards of passive smoking. FINDINGS: Two in three parents who smoked did not recognize the increased risk for an inner ear infection and approximately 50% were not aware of the role of parental smoking in recruiting smokers. One in two smokers tended to agree or agreed that an act should be passed which forbids all indoor smoking in the vicinity of children. After adjustment for covariates, the level of health-risk awareness about ETS was significantly related to no ETS exposure within and outside the home. CONCLUSION: The main findings indicate that educating parents about the established health risks of ETS for their children may significantly reduce children's exposure to ETS. An increased effort is needed to educate parents who smoke on the potential health risks of ETS for their children.

Readiness to change sun-protective behaviour.

The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden during the last 20 years. The best-known way to revert this trend is primary prevention. Matching health messages to readiness to change in the population may enhance the effect of community-based prevention. The aims of this study were to investigate readiness to change sun-protective behaviour in two groups (visitors to mobile screening units and beach-goers) and to test a single-item algorithm in assessing the stage of change in sun-protective behaviour. Seven hundred and forty-two visitors to the mobile screening units and 202 individuals on nearby beaches answered a short questionnaire. The assessment of readiness to change was based on stages of change in sun-protective behaviour modified from the Transtheoretical Model of Behaviour Change. As expected, the visitors to the screening units were more often in action/maintenance stages than the beach group for most sun-protective behaviours. In conclusion, the single-item algorithm method appears to be sensitive to assess readiness to change sun-protective behaviour, based on the Transtheoretical Model of Behaviour Change. This method can be incorporated into population surveys and may aid in developing successful skin cancer prevention programmes.

Emotional isolation: prevalence and the effect on well-being among 50-80-year-old prostate cancer patients.

OBJECTIVE: To investigate to what extent prostate cancer patients confide their emotional concerns, and whether having no one to confide in affects well-being. MATERIAL AND METHODS: A population-based study using epidemiological methods. A questionnaire was mailed to all 431 living prostate cancer patients aged 50-80 at the time of selection, diagnosed 1.5-2 years previously in Stockholm County, and 435 randomly selected men in the same age group. The questionnaire was completed anonymously. The main outcome measures included questions assessing the extent to which the men could share emotionally taxing feelings with their partner or others and questions assessing well-being. RESULTS: The questionnaire was returned by 79% of the patients and by 73% of the randomly selected men. Approximately one in five patients had no one to confide in. Of patients living with a partner, only one in 10 confided in someone other than their partner. Three out of 10 patients living in a relationship could not confide in their partner. Men having no one to confide in were less content with their life and reported poorer psychological and overall well-being compared with other men. The prostate cancer patients were not more likely to have someone to confide in than men in general. CONCLUSIONS: The results indicate that a lack of emotional support may be a problem for many prostate cancer patients and that the traditional psychosocial support offered to most cancer patients in Sweden may not reach male patients. There may be a need for a gender-adapted approach to emotional support.

Y-chromosomal STR haplotypes in Pakistani populations.

16 Y-specific STR loci have been analysed in 711 males from 12 populations in Pakistan. Individual loci showed between 4 and 10 alleles, and diversities ranged from 0.07 to 0.77. A total of 527 different haplotypes were found and the haplotype diversity ranged from 0.92 to 0.99 for the different populations. 446 haplotypes occurred in single individuals, and only 19 haplotypes were present in more than three males, but two striking examples of haplotype sharing were found, one involving 13 individuals, and the other 17. The 13 individuals were all Parsis, and 16 of the 17 were Brahuis, providing evidence for population substructuring.

mtDna and the islands of the North Atlantic: estimating the proportions of Norse and Gaelic ancestry.

A total of 1,664 new mtDNA control-region sequences were analyzed in order to estimate Gaelic and Scandinavian matrilineal ancestry in the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye and to investigate other aspects of their genetic history. A relative excess of private lineages in the Icelanders is indicative of isolation, whereas the scarcity of private lineages in Scottish island populations may be explained by recent gene flow and population decline. Differences in the frequencies of lineage clusters are observed between the Scandinavian and the Gaelic source mtDNA pools, and, on a continent-wide basis, such differences between populations seem to be associated with geography. A multidimensional scaling analysis of genetic distances, based on mtDNA lineage-cluster frequencies, groups the North Atlantic islanders with the Gaelic and the Scandinavian populations, whereas populations from the central, southern, and Baltic regions of Europe are arranged in clusters in broad agreement with their geographic locations. This pattern is highly significant, according to a Mantel correlation between genetic and geographic distances (r=.716). Admixture analyses indicate that the ancestral contributions of mtDNA lineages from Scandinavia to the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye are 37.5%, 35.5%, 11.5%, and 12.5%, respectively.

[Treating tobacco addiction. Praxis and barriers amongst Icelandic general practitioners.].

OBJECTIVE: To assess praxis and identify the most common barriers for engaging in tobacco prevention in general practice in the Nordic countries. MATERIAL AND METHODS: All 167 practicing general practitioners in Iceland received a questionnaire at home assessing praxis and barriers for systematic involvement in tobacco prevention. RESULTS: The over all response rate was 77%. Few general practitioners asked patients if they smoked if the patient had no smoking related symptoms. Few supported patients who wanted to stop smoking. However, a big majority agreed that tobacco prevention was a part of their job. The main reasons for not engaging in tobacco prevention was lack of time and the feeling that the time spent may not be worth the effort since few patients quit. A big majority stated that they would prefer to reefer smokers to smoking cessation specialist. CONCLUSIONS: Smoking cessation expertise needs to be more accessible to Icelandic patients and doctors.

Improving the preservation of erectile function after external beam radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: To investigate whether the type of collimation technique, target dose and treated volume influence the prevalence of intact erectile function after external beam radiation therapy for localized prostate cancer. PATIENTS AND METHODS: A prospective study was conducted to assess erection stiffness before treatment and after follow-ups of 9-18 months and 4-5.5 years. Information was collected using the Radiumhemmet Scale of Sexual Function. RESULTS: Thirty-one men were 'potent' before the radiation. Fourteen of them were treated with a conventional collimator and 17 were given three-dimensional conformal therapy with the aid of a multileaf collimator. Preserved erectile function at 9-18 months was found in 17 of the 31 men (55%) and at the 4-5-year follow-up in five of 22 (23%). Preservation of potency was related to the treatment procedure but not to the treatment volume. CONCLUSIONS: Conformal therapy may increase the percentage of men preserving erectile function during radiotherapy for localized prostate cancer; it is possible that the differences to conventional therapy do not depend on treated volume.

Estimating Scandinavian and Gaelic ancestry in the male settlers of Iceland.

We present findings based on a study of Y-chromosome diallelic and microsatellite variation in 181 Icelanders, 233 Scandinavians, and 283 Gaels from Ireland and Scotland. All but one of the Icelandic Y chromosomes belong to haplogroup 1 (41.4%), haplogroup 2 (34.2%), or haplogroup 3 (23.8%). We present phylogenetic networks of Icelandic Y-chromosome variation, using haplotypes constructed from seven diallelic markers and eight microsatellite markers, and we propose two new clades. We also report, for the first time, the phylogenetic context of the microsatellite marker DYS385 in Europe. A comparison of haplotypes based on six diallelic loci and five microsatellite loci indicates that some Icelandic haplogroup-1 chromosomes are likely to have a Gaelic origin, whereas for most Icelandic haplogroup-2 and -3 chromosomes, a Scandinavian origin is probable. The data suggest that 20%-25% of Icelandic founding males had Gaelic ancestry, with the remainder having Norse ancestry. The closer relationship with the Scandinavian Y-chromosome pool is supported by the results of analyses of genetic distances and lineage sharing. These findings contrast with results based on mtDNA data, which indicate closer matrilineal links with populations of the British Isles. This supports the model, put forward by some historians, that the majority of females in the Icelandic founding population had Gaelic ancestry, whereas the majority of males had Scandinavian ancestry.

[Do health personnel talk about passive smoking with parents of small children?]. / Snakker helsepersonell med småbarnsforeldre om passiv røyking?

INTRODUCTION: Almost seven out of ten parents who smoke state that they have never received information on passive smoking from health personnel when they bring their children in for routine medical examination. We examined what GPs, doctors and nurses at mother-and-child clinics and midwives reported. MATERIAL AND METHODS: A self-administered questionnaire focusing on practice as regards the matter of passive smoking and children was mailed to a representative sample of 1050 GPs, the senior midwives at Norway's 77 maternity departments, 492 senior public health nurses, and health personnel at 1024 mother-and-child clinics. The response rate varied from 71% (GPs) to 82% (senior midwives). RESULTS: 70% of the personnel at mother-and-child clinics less often than "always" ask about exposure to passive smoking. 60% of the senior midwives report that the department's personnel less than "to a large extent" allocate time to talk with parents about passive smoking. 40% of the GPs and 50% of the paediatricians say that they "never" bring up the matter of passive smoking when they examine small children and do not know whether members of the household smoke or not. The rest of the GPs bring up the matter in 46% of consultations and the rest of the paediatricians in 63% of consultations. When the child has symptoms that can be associated with passive smoking, the GPs discuss the parents' smoking habits in 88% of the consultations and paediatricians in 100% of consultations. INTERPRETATION: Only to a small extent do health personnel use their opportunities of motivating parents to change their smoking habits for the sake of the health of their children. Smoking is only brought up by professionals as a matter routine when the children develop symptoms of exposure to tobacco smoke.

[Why do health personnel neglect to talk about passive smoking with parents of small children?]. / Hvorfor unnlater helsepersonell å snakke med småbarnsforeldre om passiv røyking?

BACKGROUND: Health personnel make only moderate efforts at motivating parents to establish a smoke-free indoor environment for babies and infants. It is only when children show symptoms of exposure to tobacco smoke that they routinely raise the question of passive smoking during consultations with the parents. We wanted to find out why so many neglect to raise the matter when there is still time to prevent injury to the child. MATERIAL AND METHODS: A pre-categorised questionnaire on possible obstacles to involvement in the matter was mailed to a representative sample of 1050 GPs, the senior midwives at Norway's 77 maternity departments, 492 senior public health nurses, and personnel at 1024 mother-and-child clinics. The response rate varied from 71% (GPs) to 82% (senior midwives). RESULTS: Public health nurses, midwives and doctors at the clinics regard it as part of their work to talk to parents about the possible effects of passive smoking on their children's health. The obstacles are a feeling of embarrassment at raising the matter, and not knowing how to talk to the parents about the problem. Even so, a clear majority experience a positive response from smoking parents when they discuss how to prevent the children from inhaling tobacco smoke. Among the GPs the main reason for not raising the matter is lack of time, followed by embarrassment at taking it up and lack of knowledge about the health risks. INTERPRETATION: Health personnel seem to need training in conversation techniques in this connection.

The mutation rate in the human mtDNA control region.

The mutation rate of the mitochondrial control region has been widely used to calibrate human population history. However, estimates of the mutation rate in this region have spanned two orders of magnitude. To readdress this rate, we sequenced the mtDNA control region in 272 individuals, who were related by a total of 705 mtDNA transmission events, from 26 large Icelandic pedigrees. Three base substitutions were observed, and the mutation rate across the two hypervariable regions was estimated to be 3/705 =.0043 per generation (95% confidence interval [CI].00088-.013), or.32/site/1 million years (95% CI.065-.97). This study is substantially larger than others published, which have directly assessed mtDNA mutation rates on the basis of pedigrees, and the estimated mutation rate is intermediate among those derived from pedigree-based studies. Our estimated rate remains higher than those based on phylogenetic comparisons. We discuss possible reasons for-and consequences of-this discrepancy. The present study also provides information on rates of insertion/deletion mutations, rates of heteroplasmy, and the reliability of maternal links in the Icelandic genealogy database.

mtDNA and the origin of the Icelanders: deciphering signals of recent population history.

Previous attempts to investigate the origin of the Icelanders have provided estimates of ancestry ranging from a 98% British Isles contribution to an 86% Scandinavian contribution. We generated mitochondrial sequence data for 401 Icelandic individuals and compared these data with >2,500 other European sequences from published sources, to determine the probable origins of women who contributed to Iceland's settlement. Although the mean number of base-pair differences is high in the Icelandic sequences and they are widely distributed in the overall European mtDNA phylogeny, we find a smaller number of distinct mitochondrial lineages, compared with most other European populations. The frequencies of a number of mtDNA lineages in the Icelanders deviate noticeably from those in neighboring populations, suggesting that founder effects and genetic drift may have had a considerable influence on the Icelandic gene pool. This is in accordance with available demographic evidence about Icelandic population history. A comparison with published mtDNA lineages from European populations indicates that, whereas most founding females probably originated from Scandinavia and the British Isles, lesser contributions from other populations may also have taken place. We present a highly resolved phylogenetic network for the Icelandic data, identifying a number of previously unreported mtDNA lineage clusters and providing a detailed depiction of the evolutionary relationships between European mtDNA clusters. Our findings indicate that European populations contain a large number of closely related mitochondrial lineages, many of which have not yet been sampled in the current comparative data set. Consequently, substantial increases in sample sizes that use mtDNA data will be needed to obtain valid estimates of the diverse ancestral mixtures that ultimately gave rise to contemporary populations.