| 1. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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| 2. |
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| 3. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 4. |
- Jin, Guangfu, et al.
(författare)
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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
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:7, s. 1095-1103
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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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| 5. |
- Lu, Lingyi, et al.
(författare)
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Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
- 2012
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:4, s. 410-426
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.
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| 6. |
- Rehm, Jürgen, et al.
(författare)
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Classifying alcohol control policies enacted between 2000 and 2020 in Poland and the Baltic countries to model potential impact
- 2023
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 118:3, s. 449-458
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The study's aim is to identify and classify the most important alcohol control policies in the Baltic countries (Estonia, Latvia and Lithuania) and Poland between 2000 and 2020.Methods: Policy analysis of Baltic countries and Poland, predicting potential policy impact on alcohol consumption, all-cause mortality and alcohol-attributable hospitalizations was discussed.Results: All Baltic countries implemented stringent availability restrictions on off-premises trading hours and different degrees of taxation increases to reduce the affordability of alcoholic beverages, as well as various degrees of bans on alcohol marketing. In contrast, Poland implemented few excise taxation increases or availability restrictions and, in fact, reduced stipulations on prior marketing bans.Conclusions: This classification of alcohol control policies in the Baltic countries and Poland provides a basis for future modeling of the impact of implementing effective alcohol control policies (Baltic countries), as well as the effects of loosening such policies (Poland).
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| 7. |
- Rehm, Jürgen, et al.
(författare)
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Classifying Alcohol Control Policies with Respect to Expected Changes in Consumption and Alcohol-Attributable Harm : The Example of Lithuania, 2000-2019
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Due to the high levels of alcohol use, alcohol-attributable mortality and burden of disease, and detrimental drinking patterns, Lithuania implemented a series of alcohol control policies within a relatively short period of time, between 2008 and 2019. Based on their expected impact on alcohol consumption and alcohol-attributable harm, as well as their target population, these policies have been classified using a set of objective criteria and expert opinion. The classification criteria included: positive vs. negative outcomes, mainly immediate vs. delayed outcomes, and general population vs. specific group outcomes. The judgement of the alcohol policy experts converged on the objective criteria, and, as a result, two tiers of intervention were identified: Tier 1—highly effective general population interventions with an anticipated immediate impact; Tier 2—other interventions aimed at the general population. In addition, interventions directed at specific populations were identified. This adaptable methodological approach to alcohol control policy classification is intended to provide guidance and support for the evaluation of alcohol policies elsewhere, to lay the foundation for the critical assessment of the policies to improve health and increase life expectancy, and to reduce crime and violence.
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| 8. |
- Rehm, Jürgen, et al.
(författare)
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Do alcohol control policies have the predicted effects on consumption? An analysis of the Baltic countries and Poland 2000–2020
- 2022
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Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 241
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many population-based alcohol control policies are postulated to work via changes in adult alcohol per capita consumption (APC). However, since APC is usually assessed on a yearly basis, often there are not enough data to conduct interrupted time-series or other controlled analyses. The current dataset, with 21 years of observation from four countries (Estonia, Latvia, Lithuania, and Poland), had sufficient power to test for average effects and potential interactions of the World Health Organization’s (WHO) three “best buys” for alcohol control: taxation increases leading to a decrease in affordability; reduced availability (via a decrease in opening hours of at least 20 %); and advertising and marketing restrictions. We postulated that the former two would have immediate effects, while the latter would have mid- to long-term effects.Methods: Linear regression analysis.Results: Taxation increases and availability reductions in all countries were associated with an average reduction in APC of 0.83 litres (ℓ) of pure alcohol per year (95 % confidence interval: −1.21 ℓ, −0.41 ℓ) in the same year, with no significant differences between countries. Restrictions on advertising and/or marketing had no significant immediate associations with APC (average effect 0.04 ℓ per year; 95 % confidence interval: −0.65 ℓ, 0.73 ℓ). Several sensitivity analyses corroborated these main results.Conclusions: The WHO “best buy” alcohol control policies of taxation increases and availability restrictions worked as postulated in these four northeastern European Union countries.
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| 9. |
- Rehm, Jürgen, et al.
(författare)
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Impact of the WHO "best buys" for alcohol policy on consumption and health in the Baltic countries and Poland 2000-2020
- 2023
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Ingår i: The Lancet Regional Health. - 2666-7762. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol use is a major risk factor for burden of disease. This narrative review aims to document the effects of major alcohol control policies, in particular taxation increases and availability restrictions in the three Baltic countries (Estonia, Latvia, and Lithuania) between 2000 and 2020. These measures have been successful in curbing alcohol sales, in general without increasing consumption of alcoholic beverages from unrecorded sources; although for more recent changes this may have been partly due to the COVID-19 pandemic. Moreover, findings from time -series analyses suggest improved health, measured as reductions in all -cause and alcohol -attributable mortality, as well as narrowing absolute mortality inequalities between lower and higher educated groups. For most outcomes, there were sex differences observed, with alcohol control policies more strongly affecting males. In contrast to this successful path, alcohol control policies were mostly dismantled in the neighbouring country of Poland, resulting in a rising death toll due to liver cirrhosis and other alcohol -attributable deaths. The natural experiment in this region of high -income European countries with high consumption levels highlights the importance of effective alcohol control policies for improving population health.
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| 10. |
- Rehm, Jürgen, et al.
(författare)
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Using Direct and Indirect Estimates for Alcohol-Attributable Mortality : A Modelling Study Using the Example of Lithuania
- 2023
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Ingår i: European Addiction Research. - : S. Karger AG. - 1022-6877 .- 1421-9891. ; 29:2, s. 119-126
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Comparative risk assessments (CRAs) for alcohol use are based on indirect estimates of attributable harm, and usually combine country-specific exposure estimates and global risk relations derived from meta-analyses. CRAs for Eastern European countries, such as Lithuania, base their risk relations not on global risk relations, but on a large Russian cohort study. The availability of a direct estimate of alcohol-attributable mortality following the 2017 implementation of a large increase in alcohol excise taxes in Lithuania has allowed a comparison of these indirect estimates with a country-specific gold standard. Methods: A statistical modelling study compared direct (predictions based on a time-series methodology) and indirect (predictions based on an attributable-fraction methodology) estimates of alcohol-attributable mortality before and after a large increase in alcohol excise taxes in Lithuania. Specifically, Russia-specific versus global relative risks were compared against the gold standard of time-series based predictions. Results: Compared to direct estimates, indirect estimates markedly underestimated the reduction of alcohol-attributable mortality 12 months post intervention by at least 63%. While both of the indirect estimates differed markedly from the direct estimates, the Russia-specific estimates were closer to the direct estimates, primarily due to higher estimates for alcohol-attributable cardiovascular mortality. Discussion: As all indirect estimates were markedly lower than direct estimates, current overall relative risks and price elasticities should be re-evaluated. In particular, global estimates should be replaced by new regional estimates based on cohort studies.
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