| 1. |
- Brandt, Andreas, et al.
(författare)
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Age at Diagnosis and Age at Death in Familial Prostate Cancer
- 2009
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 14:12, s. 1209-1217
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. A family history of prostate cancer is associated with a higher risk for prostate cancer to first-degree relatives. If greater surveillance of men at familial risk is considered to be useful, population-based estimates of the differences in the age at diagnosis between familial and sporadic prostate cancer cases are needed. Methods. The men in the nationwide Swedish Family-Cancer Database were classified according to the number and type of affected first-degree relatives (father or brother) and according to the relative's age at diagnosis. The cumulative incidence of prostate cancer and cumulative prostate cancer-specific mortality were estimated using a stratified Cox model. Results. The cumulative incidence was highest for men with multiple affected first-degree relatives, and it was higher for brothers than for sons of prostate cancer patients. The age to reach the same cumulative incidence as the general population at age 55 years decreased with decreasing age at diagnosis of the relative, ranging from 48.7 years (father diagnosed before 60 years of age) to 53.7 years (father diagnosed after 82 years of age). Prostate cancer-specific mortality was also related to the number and type of affected relatives but there was no clear evidence for a dependency on the age at diagnosis of the relative. Conclusions. Men with a father or a brother affected by prostate cancer are diagnosed and die at earlier ages than men without a family history of prostate cancer. This study should encourage further analysis in order to assess the risks and benefits of screening for prostate cancer in men at higher risk. The Oncologist 2009; 14: 1209-1217
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| 2. |
- Brendle, Annika, et al.
(författare)
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Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
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Tidskriftsartikel (refereegranskat)abstract
- Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
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| 3. |
- Brendle, Annika, et al.
(författare)
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Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer : a Swedish prospective case-control study.
- 2009
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Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:3, s. 435-442
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.
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| 4. |
- Castro, Felipe A, et al.
(författare)
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Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach.
- 2009
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 125:8, s. 1851-1858
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Tidskriftsartikel (refereegranskat)abstract
- High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (c) 2009 UICC.
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| 5. |
- Försti, Asta, et al.
(författare)
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Polymorphisms in the KDR and POSTN genes : association with breast cancer susceptibility and prognosis.
- 2007
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 101:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke. Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting. Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke. Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.
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| 6. |
- Hemminki, Kari, et al.
(författare)
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Associated cancers in parents and offspring of polycythaemia vera and myelofibrosis patients
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 147:4, s. 526-530
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Tidskriftsartikel (refereegranskat)abstract
- Polycythaemia vera (PV) and primary myelofibrosis (MF) show concordant familial clustering but limited population level data are available on the aggregation of other discordant neoplasms in these families. We used the Swedish Family-Cancer Database to assess risks for VP and MF in families of cancer patients. A total of 3530 first PV and 1606 MF patients were identified, with high concordant familial risks. Several discordant familial associations were found for PV (acute myeloid leukaemia, Hodgkin disease, prostate and bladder cancers) or for MF (chronic lymphatic leukaemia, colorectal, kidney and cervical cancers) or for both (nervous system, eye and endocrine tumours).
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| 7. |
- Hemminki, Kari, et al.
(författare)
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Concordance of survival in family members with prostate cancer
- 2008
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:10, s. 1705-1709
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Several earlier studies have assessed survival in prostate cancer based on familial risk of this disease. As a novel concept, we posit that factors governing survival in prostate cancer are likely to be different from those governing risk of prostate cancer. To prove this, we searched for familial clustering of survival (ie, concordance of survival among family members).PATIENTS AND METHODS: We used the nationwide Swedish Family-Cancer Database to estimate hazard rates (HRs) for cause-specific and overall survival in invasive prostate cancer. HRs show the probability of death in the study group compared with the reference group. The study covered 610 sons of affected fathers with median follow-up times for survival ranging from 34 to 76 months.RESULTS: When the survival in sons was analyzed according to the fathers' length of survival, there was a concordance of prognosis; the HR was 0.62 for sons whose fathers had survived longer than 59 months, compared with sons whose fathers had survived fewer than 24 months (P for trend, .02). On a continuous scale, the sons' survival increased almost linearly with the fathers' survival time. When the analysis was reversed and HRs were derived for fathers, the concordance of good and poor survival remained.CONCLUSION: The results are consistent in showing that both good and poor survival in prostate cancer aggregate in families. Genetic factors are likely to contribute to the results, which provide the first challenging population-level evidence on heritability in prognosis of prostate cancer.
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| 8. |
- Hemminki, Kari, et al.
(författare)
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Familial risks for hospitalized Graves' disease and goiter
- 2009
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 161:4, s. 623-629
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Familial Clustering of a disease is an indicator of a possible heritable Cause. provided that environmental sharing can be excluded. Thus. data on familial risks are important For genetic Studies and for clinical genetic counseling. Design: We carried Out a nationwide family study on nontoxic and toxic nodular goiters, and Graves' disease in order to search for familial clustering of these diseases at the population level. Methods: The Swedish Multigeneration Register on 0-75 year old Subjects was linked to the Hospital Discharge Register from years 1987 to 2007. Standardized incidence ratios (SIRs) were calculated for offspring of affected parents and for siblings by comparing to those whose relatives had no hospitalization for thyroid disease. Results: The number of hospitalized patients in the offspring generations was 11 659 for nontoxic goiter, 9514 for Graves' disease, and 1728 For toxic nodular goiter. Familial Cases accounted for 8.2, 5.2, and 2.1% of all patients respectively The highest familial risk for offspring of affected parents was noted for Graves' disease (SIR 3.87), followed by toxic nodular goiter (3.37) and nontoxic goiter (3.15). Familial risks were higher for affected siblings: toxic nodular goiter (11.66). Graves' disease (5.51). and nontoxic goiter (5.40). Weaker familial associations were observed between the three diseases. Conclusions: To Our knowledge this is it first population-based family study On these thyroid diseases. The observed high familial aggregation for defined thyroid diseases cannot be explained by the known genetic basis, calling for further Studies into genetic and environmental etiology of thyroid diseases.
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| 9. |
- Hemminki, Kari, et al.
(författare)
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Familial risks in nervous-system tumours: a histology-specific analysis from Sweden and Norway
- 2009
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Ingår i: The Lancet Oncology. - 1474-5488. ; 10:5, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Background There are limited data available on tumour subtype-specific familial risks for nervous-system tumours. We aimed to provide such data at the population level. Methods We used data from the nationwide Swedish and Norwegian databases on familial cancer to calculate standardised incidence ratios (SIRS) for the familial risk of developing a nervous-system tumour in offspring born after 1931 (Sweden) or 1900 (Norway) whose parents or siblings were probands. Findings 54195 patients had nervous-system tumours, 22331 of whom belonged to the offspring generation aged 0-72 years in Sweden and 0-51 years in Norway. Of 709 familial patients in the offspring generation, 438 (61.8%) had a parent affected by a nervous-system tumour (SIR 1.66; 95% CI 1.51-1.82), 236 (33.3%) had a sibling affected by a nervous-system tumour (SIR 2.01; 95% CI 1.76-2.28), and 35 (4.9%) belonged to families with a parent and at least two siblings affected by a nervous-system tumour (multiplex families; SIR 13.40; 95% CI 9.33-18.66). The SIR for glioma was 1.8 (1.5-2.0) when a parent was a proband, but increased to 11.2 (5.7-19.5) in multiplex families. Early-onset neurinoma and haemangioma showed high familial risks; with an SIR for neurinoma of 1.7 (1.4-2.2) for offspring of affected parents, 2.7 (2.0-3.5) for siblings, and 27.2 (13.5-48.8) for multiplex families, and an SIR for haemangioma of 2.4 (1.4-3.8) for offspring of affected parents. Histology-specific population-based familial risks were shown for meningioma (1.6 for offspring of affected parents; 95% CI 1.3-2.0), ependymoma (2.7 for young offspring <20 years; 1.1-5.5), medulloblastoma (4.1 for siblings; 1.7-8.1), and neuroblastoma (3.2 for siblings; 1.1-6.9). Interpretation Our results suggest a complex genetic background for nervous-system tumours, which differs depending on the age of onset and histological subtype of the tumour. High sibling risks might suggest recessive inheritance. As the high-penetrant multiplex families only accounted for about 5% of familial nervous-system tumours, most familial cases are probably caused by low-penetrance genes.
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| 10. |
- Hemminki, Kari, et al.
(författare)
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Risk of subsequent solid tumors after non-Hodgkin's lymphoma : effect of diagnostic age and time since diagnosis.
- 2008
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Ingår i: J Clin Oncol. - 1527-7755. ; 26:11, s. 1850-1857
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Quantitative data on subsequent cancers after primary cancers provide information on treatment-related risks on second cancers, with implications for therapeutic adverse effects and human susceptibility in general. Quantitative data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma (NHL) because the disease is diagnosed at a wide range of ages and treated uniformly primarily with chemotherapy. PATIENTS AND METHODS: The nationwide Swedish Family-Cancer Database included 11.5 million individuals whose cancers were retrieved from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent neoplasms among 28,131 patients with NHL. RESULTS: The SIR for solid tumors after NHL was 1.65 (2,290 patients) and that for lymphohematopoietic neoplasms was 5.36 (369 patients). Among the 25 most common solid tumors, the SIRs were increased for all but nine sites; the highest SIR (40.8) was observed for spinal meningioma. The SIRs for solid tumors declined in an age-dependent manner from 4.52 in diagnostic age younger than 20 years to 1.12 in diagnostic age 70+ years. In the most common patient groups, the SIRs for solid tumors increased up to 30 years after NHL diagnosis. Because of the high incidence of solid tumors in these age groups, they contributed the largest numbers of therapy-related cases. CONCLUSION: These data indicate that age at treatment determines both the magnitude of the initial relative risk and the time-dependent modulation of the response. Therapy-related damage persists at least 30 years and its toll of solid tumors is largest 21 to 30 years after diagnosis.
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