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  • Grönberg, Henrik, et al. (författare)
  • BRCA2 mutation in a family with hereditary prostate cancer
  • 2001
  • Ingår i: Genes, Chromosomes and Cancer. - John Wiley and Sons Inc.. - 1045-2257. ; 30:3, s. 299-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Hereditary prostate cancer is a genetically heterogeneous disease, and so far four different susceptibility loci have been identified. Reports of associated cancers are few, and it is generally considered a sire-specific disease. However, some reports have shown an elevated risk for prostate cancer among BRCA2 mutation carriers. In this report, we present a family in which the father and four of his sons were diagnosed with prostate cancer at exceptionally early ages (51, 52, 56, 58, and 63 years, respectively). In addition, three daughters were diagnosed with breast cancer between the ages of 47 and 61. In this family, a truncating mutation in exon 11, 6051delA of the BRCA2 gene, leading to an early termination of the protein (codon 1962), was identified. Although BRCA2 is probably responsible only for a very small fraction of hereditary prostate cancers, this finding supports previous reports of an increased risk of prostate cancer in BRCA2 mutation carriers.
  • Grönberg, Henrik, 1961- (författare)
  • Prostate cancer epidemiological studies
  • 1995
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Prostate cancer is a large and increasing medical problem both in Sweden and in the rest of the developed world, with about 300.000 new cases diagnosed world wide annually. Despite the high incidence of this disease, little is known about the aetiology of prostate cancer. The aim of this study was to try to understand more about the natural history and to find possible a etiological risk factors for this tumour.In a population based study of prostate cancer cases in northern Sweden it was found that the large increase in prostate cancer during the last two decades was mainly caused by well (Gl) and moderately (G2) differentiated tumours. However, the incidence of poorly differentiated (G3) tumours remained unchanged. The introduction of new diagnostic methods is the most plausible explanation for the increase of these low grade tumours.The relative survival in prostate cancer was found to be independent of patient age at diagnosis, indicating that tumour proliferation and the aggressiveness of this disease is equal in all ages. However, due to the increasing occurrence of concurrent diseases with growing age the number of lost years caused by prostate cancer decreases dramatically in older age groups. The overall cause specific mortality for prostate cancer was found to be around 50%. In accordance with most other cancer tumours, the annual mortality rate decreased with longer survival also for prostate cancer patients.In a study from the Swedish Twin Register it was found that the proband concordance rates for prostate cancer were 4,5 time greater among monozygotic compared to dizygotic twins. In a large nation-wide cohort study of men who had a father with prostate cancer, the overall standardised incidence ratio (SIR) was 1.70 for prostate cancer. Younger age at diagnosis among the fathers were associated with an increased risk among sons. This cohort study and the twin study indicates that both inherited and familial factors are of importance in a subgroup of prostate cancer patients.In a prospective case-control study, both a high body mass index (BMI) and a high food intake were found to be independent risk factors for prostate cancer. Both BMI and a high food intake might be indicators of a high fat diet, which so far is the most consistent exogenous risk factor for prostate cancer. The use of tobacco or alcoholic beverages were not associated with prostate cancer risk.
  • Hassler, Sven, et al. (författare)
  • Cancer in the Sami population of Sweden in relation to lifestyle and genetic factors
  • 2008
  • Ingår i: European Journal of Epidemiology. - 0393-2990. ; 23:4, s. 273-280
  • Tidskriftsartikel (refereegranskat)abstract
    • The reindeer herding Sami of Sweden have low incidences of cancer. The aim of the present study was to investigate the cancer risk in a large cohort of Swedish Sami, containing Sami with different lifestyle and genetic Sami heritage. A cohort of 41,721 Sami identified in official national registers between 1960 and 1997, was divided into two sub-populations - reindeer herding Sami (RS) and non-reindeer herding Sami (NRS). A demographically matched non-Sami reference population (NS) was used as standard when incidence and mortality ratios were calculated. Incidence and mortality data were obtained from the Swedish Cancer and Cause of Death Registers for the period 1961–2003. For Sami men, lower risks were found for cancers of the colon and prostate, and for malignant melanoma and non-Hodkins lymphoma, but higher for stomach cancer. The Sami women showed higher risks for cancers of the stomach and the ovaries, but lower risk for cancer of the bladder. The RS demonstrated lower relative cancer risks compared with the NRS. The lowest relative risk was found among the RS men, while the highest were observed among the NRS women. The RS men who had adopted a more westernized lifestyle showed a similar relative risk for prostate cancer as that of the NS living in the same region. Most of these differences in cancer risks could probably be ascribed to differences in lifestyle. It is concluded that the traditional Sami lifestyle contains elements, e.g. dietary contents and physical activity that may protect them from developing cancer.
  • Hassler, Sven, et al. (författare)
  • Causes of death in the Sami population of Sweden, 1961-2000.
  • 2005
  • Ingår i: International Journal of Epidemiology. - 0300-5771. ; 34:3, s. 623-629
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Indigenous people often have a pattern of mortality that is disadvantageous in comparison with the general population. The knowledge on causes of death among the Sami, the natives of northern Scandinavia, is limited. The aim of the present study was to compare gender and cause specific mortality patterns for reindeer herding Sami, non-herding Sami, and non-Sami between 1961 and 2000. METHODS: A Sami cohort was constructed departing from a group of index-Sami identified as either reindeer herding Sami or Sami eligible to vote for the Sami parliament. Relatives of index-Sami were identified in the National Kinship Register and added to the cohort. The cohort contained a total of 41 721 people (7482 reindeer herding Sami and 34 239 non-herding Sami). A demographically matched non-Sami reference population four times as large, was compiled in the same way. Relative mortality risks were analysed by calculating standardized mortality ratios (SMRs). RESULTS: The differences in overall mortality and life expectancy of the Sami, both reindeer herding and non-herding, compared with the reference population were relatively small. However, Sami men showed significantly lower SMR for cancers but higher for external causes of injury. For Sami women, significantly higher SMR was found for diseases of the circulatory system and diseases of the respiratory system. An increased risk of dying from subarachnoid haemorrhage was observed among both Sami men and women. CONCLUSIONS: The similarities in mortality patterns are probably a result of centuries of close interaction between the Sami and the non-Sami, while the observed differences might be due to lifestyle, psychosocial and/or genetic factors.
  • Hassler, Sven, et al. (författare)
  • Fatal accidents and suicide among reindeer-herding Sami in Sweden
  • 2004
  • Ingår i: International Journal of Circumpolar Health. - 1239-9736. ; 63 Suppl 2, s. 384-388
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Over the last decades, reindeer-herding management has experienced drarnatic changes, e.g. increased motorization and socio-econornic pressure. The airn of the present study was to investigate whether these changes have increased the risk of fatal, work-related accidents and suicide between 1961 and 2000. Study design and methods. A c oh ort containing 7,482 members of reindeer-herding Sami families was extracted from national population registers. Information on fatal accidents and suicide was obtained from the Swedish Causes of Death Register, and compared to the expected number of deaths in a dernographica11y matched control population of non-Sami. Results. The ffiale reindeer her- ding Sami showed a significantly increased risk of dying from accidents such as vehicle accidents and poisoning. No significant increased risk of suicide was observed. A comparison between the periods of 1961-1980 and 1981- 2000 showed non-significant differences in risk, although a trend towards incre- ased risks was observed for most types of external causes of death except suicide. Conclusions. It is suggested that the increased socio-econornic pressure and the extensive use of terrain vehicles have increased the risk for fatal accidents arnong Swedish reindeer herders, and that commercial reindeer ma- nagement is one of the most dangerous occupations in Sweden
  • Hedelin, Maria, et al. (författare)
  • Dietary phytoestrogen, serum enterolactone and risk of prostate cancer : the cancer prostate Sweden study (Sweden)
  • 2006
  • Ingår i: Cancer Causes and Control. - Springer. - 0957-5243. ; 17:2, s. 169-180
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. METHODS: In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. RESULTS: High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35-1.14) and 0.74 (95% CI: 0.41-1.32). CONCLUSIONS: Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.
  • Hong, Mun-Gwan, et al. (författare)
  • A genome-wide assessment of variability in human serum metabolism
  • 2013
  • Ingår i: Human mutation. - 1098-1004. ; 34:3, s. 515-524
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of the genetic regulation of metabolism in human serum samples can contribute to a better understanding of the intermediate biological steps that lead from polymorphism to disease. Here, we conducted a genome-wide association study (GWAS) to discover metabolic quantitative trait loci (mQTLs) utilizing samples from a study of prostate cancer in Swedish men, consisting of 402 individuals (214 cases and 188 controls) in a discovery set and 489 case-only samples in a replication set. A global nontargeted metabolite profiling approach was utilized resulting in the detection of 6,138 molecular features followed by targeted identification of associated metabolites. Seven replicating loci were identified (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with associated sequence variants contributing significantly to trait variance for one or more metabolites (P = 10(-13) -10(-91)). Regional mQTL enrichment analyses implicated two loci that included FADS1 and a novel locus near PDGFC. Biological pathway analysis implicated ACADM, ACADS, ACAD8, ACAD10, ACAD11, and ACOXL, reflecting significant enrichment of genes with acyl-CoA dehydrogenase activity. mQTL SNPs and mQTL-harboring genes were over-represented across GWASs conducted to date, suggesting that these data may have utility in tracing the molecular basis of some complex disease associations.
  • Hsu, Fang-Chi, et al. (författare)
  • A novel prostate cancer susceptibility locus at 19q13.
  • 2009
  • Ingår i: Cancer research. - 1538-7445. ; 69:7, s. 2720-3
  • Tidskriftsartikel (refereegranskat)abstract
    • A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (n=2,393) and controls (n=1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P=9.4 x 10(-4)). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 x 10(-7) from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.
  • Jin, Guangfu, et al. (författare)
  • Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis : evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)
  • 2012
  • Ingår i: Human Genetics. - 0340-6717. ; 131:7, s. 1095-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.
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