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- Luczynska, Anna, et al.
(författare)
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Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: American Journal of Clinical Nutrition. - Rockville Pike, Bethesda, MD, USA : Elsevier BV. - 1938-3207 .- 0002-9165. ; 98:3, s. 827-838
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relation between vitamin D status and lymphoma risk is inconclusive. Objective: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. Design: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. Results: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with >= 2y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Conclusions: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.
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| 2. |
- Melin, Beatrice, et al.
(författare)
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Genetics in glioma : lessons learned from genome-wide association studies
- 2013
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Ingår i: Current Opinion in Neurology. - : Lippincott Williams & Wilkins. - 1350-7540 .- 1473-6551. ; 26:6, s. 688-692
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review The purpose of this review is to describe the recent knowledge gathered from the identification of seven genomic regions that have been linked to the risk of developing malignant glioma. Recent findings The recent novel discoveries in fine mapping and genotype-phenotype studies will be highlighted. Through imputation and next-generation sequencing a novel genetic variant, rs55705857, with a strong association at 8q24 has been discovered and validated in two studies. This locus is specifically associated with IDH1-mutated and IDH2-mutated tumors and oligodendroglial tumors, albeit the specific mechanism of tumor development is not understood. The genetic variants associated with the risk of glioma in the EGFR gene have also been associated with specific somatic aberrations, including loss at the CDKN2A/B locus and allele specific loss of EGFR in the tumors. A specific TP53 low frequency variant has also been associated with glioma risk and validated in a separate data set. The genetic risk in the telomere regulating genes TERT and RTEL appear to be associated with higher grade tumors without IDH mutations. Summary The link of genetic loci to specific tumor subtypes may have relevance for understanding glioma biology, and for developing new diagnostic tools and targeted therapy for glioma.
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| 3. |
- Melin, Beatrice, et al.
(författare)
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Known glioma risk loci are associated with glioma with a family history of brain tumours : a case-control gene association study
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:10, s. 2464-2468
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Tidskriftsartikel (refereegranskat)abstract
- Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four casecontrol studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in casecontrol designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.250.61; Bonferroni adjusted ptrend, 1.7 x 104). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.
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| 4. |
- Sadetzki, Siegal, et al.
(författare)
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Description of selected characteristics of familial glioma patients : Results from the Gliogene Consortium
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:6, s. 1335-1345
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Tidskriftsartikel (refereegranskat)abstract
- Background: While certain inherited syndromes (e. g. Neurofibromatosis or LiFraumeni) are associated with an increased risk of glioma, most familial gliomas are nonsyndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. Methods: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. Findings: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (+/- standard deviation [SD]) diagnosis age was 49.4 (+/- 18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at < 40 y, and in 12% both were diagnosed under 40 y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17 y younger than those with grades III-IV. Interpretation: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma. (C) 2012 Elsevier Ltd. All rights reserved.
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