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Siegal Sadetzki,
Revital Bruchim,
Bernice Oberman,
Georgina N Armstrong,
Ching C Lau,
Elizabeth B Claus,
Jill S Barnholtz-Sloan,
Dora Il'yasova,
Joellen Schildkraut,
Christoffer Johansen, [......],
Robert B Jenkins,
Daniel Lachance,
Nicholas A Vick,
Ryan Merrell,
Margaret Wrensch,
Faith G Davis,
Bridget J McCarthy,
Rose Lai, Beatrice S Melin,
Melissa L Bondy
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ABSTRACT: BACKGROUND: While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. 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 <40y, and in 12% both were diagnosed under 40y 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 17y 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.
European journal of cancer (Oxford, England: 1990) 01/2013; · 4.12 Impact Factor
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Yanhong Liu, Beatrice S Melin,
Preetha Rajaraman,
Zhaoming Wang,
Martha Linet,
Sanjay Shete,
Christopher I Amos,
Ching C Lau,
Michael E Scheurer,
Spiridon Tsavachidis, [......],
Robert B Jenkins,
Daniel LaChance,
Nicholas A Vick,
Margaret Wrensch,
Faith Davis,
Bridget J McCarthy,
Ulrika Andersson,
Patricia A Thompson,
Stephen Chanock,
Melissa L Bondy
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ABSTRACT: The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P(trend) <1.0 × 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.
Human Genetics 06/2012; 131(9):1507-17. · 5.07 Impact Factor
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ABSTRACT: Telomere biology is associated with cancer initiation and prognosis. Collected data suggest that blood cell telomere length (TL) can change over time, which may be related to development of common disorders, such as cardiovascular diseases and cancer. Recently, single nucleotide polymorphisms in the region of the human telomerase reverse transcriptase (hTERT) gene were associated with various malignancies, including glioma, lung and urinary bladder cancer, and telomerase RNA gene hTERC genotypes were recently linked to TL. In the present study a hypothetical association between identified genotypes in hTERT and hTERC genes and TL were investigated. We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the hTERT gene, two genetic variants in hTERC, and relative TL(RTL) at average age 50 and 60 in 959 individuals with repeated blood samples. Mean RTL at age 60 was associated with four genetic variants of the hTERT gene (rs2736100, rs2853672, rs2853677, and rs2853676), two of which reported to be associated with cancer risk. Two alleles (rs12696304, rs16847897) near the hTERC gene were confirmed as also being associated with RTL at age 60. Our data suggest that hTERT and hTERC genotypes have an impact on TL of potential relevance and detectable first at higher ages, which gives us further insight to the complex regulation of TL.
Genetic Epidemiology 05/2012; 36(4):368-72. · 3.44 Impact Factor
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Sanjay Shete,
Ching C Lau,
Richard S Houlston,
Elizabeth B Claus,
Jill Barnholtz-Sloan,
Rose Lai,
Dora Il'yasova,
Joellen Schildkraut,
Siegal Sadetzki,
Christoffer Johansen, [......],
Eastwood Hon-chiu Leung,
Caleb Davis,
Rita Cheng,
Fay J Hosking,
Georgina N Armstrong,
Yanhong Liu,
Robert K Yu,
Roger Henriksson, Beatrice S Melin,
Melissa L Bondy
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ABSTRACT: Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma.
Cancer Research 12/2011; 71(24):7568-75. · 7.86 Impact Factor
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Carl Wibom,
Sara Sjöström,
Roger Henriksson,
Thomas Brännström,
Helle Broholm,
Patrik Rydén,
Christoffer Johansen,
Helle Collatz-Laier,
Sara Hepworth,
Patricia A McKinney,
Lara Bethke,
Richard S Houlston,
Ulrika Andersson, Beatrice S Melin
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ABSTRACT: Patient outcome from glioma may be influenced by germline variation. Considering the importance of DNA repair in cancer biology as well as in response to treatment, we studied the relationship between 1458 SNPs, which captured the majority of the common genetic variation in 136 DNA repair genes, in 138 glioblastoma samples from Sweden and Denmark. We confirmed our findings in an independent cohort of 121 glioblastoma patients from the UK. Our analysis revealed nine SNPs annotating MSH2, RAD51L1 and RECQL4 that were significantly (p < 0.05) associated with glioblastoma survival.
Acta oncologica (Stockholm, Sweden) 10/2011; 51(3):325-32. · 2.27 Impact Factor
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Sabine Rohrmann,
Jakob Linseisen,
Susen Becker,
Naomi Allen,
Brigitte Schlehofer,
Kim Overvad,
Anja Olsen,
Anne Tjønneland, Beatrice S Melin,
Eiliv Lund, [......],
Petra H M Peeters,
Kay-Tee Khaw,
Nicholas J Wareham,
Timothy J Key,
Sabina Rinaldi,
Isabelle Romieux,
Valentina Gallo,
Dominique S Michaud,
Elio Riboli,
Rudolf Kaaks
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ABSTRACT: Insulin-like growth factor-1 (IGF-I) is important in normal brain development but in the adult brain, IGF-I overexpression may be a risk factor for tumor development.
We examined the association between circulating concentrations of IGF-I and IGFBP-3 in relation to risk of gliomas (74 low-grade, 206 high-grade gliomas), meningiomas (n = 174) and acoustic neuromas (n = 49) by using a case-control design nested in the European Prospective Investigation into Cancer and Nutrition. IGF-I and IGFBP-3 were measured by ELISAs.Conditional logistic regression was used to compute ORs and corresponding 95% CIs.
The risk of low-grade gliomas was elevated with increased IGF-I (OR = 3.60, 95% CI: 1.11-11.7; top vs. bottom quartile) and decreased with elevated IGFBP-3 concentrations (OR = 0.28, 95% CI: 0.09-0.84) after mutual adjustment of these two factors; these results became nonsignificant after exclusion of the first year of follow-up. No association was observed for high-grade gliomas or meningiomas. Both high IGF-I and IGFBP-3 concentrations were associated with risk of acoustic neuromas (IGF-I: OR = 6.63, 95% CI: 2.27-19.4, top vs. bottom tertile; IGFBP-3: OR = 7.07, 95% CI: 2.32-21.6), even after excluding the first year of follow-up.
High concentrations of IGF-I might be positively associated with risk of low-grade gliomas and acoustic neuromas, although we cannot exclude reverse causation, in particular for low-grade gliomas.
Factors of the IGF axis might be involved in the etiology of some types of brain tumors.
Cancer Epidemiology Biomarkers & Prevention 08/2011; 20(10):2174-82. · 4.12 Impact Factor
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ABSTRACT: Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.
Cancer Causes and Control 06/2011; 22(9):1259-66. · 2.88 Impact Factor
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Shala Ghaderi Berntsson,
Carl Wibom,
Sara Sjöström,
Roger Henriksson,
Thomas Brännström,
Helle Broholm,
Christoffer Johansson,
Sarah J Fleming,
Patricia A McKinney,
Lara Bethke,
Richard Houlston,
Anja Smits,
Ulrika Andersson, Beatrice S Melin
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ABSTRACT: The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.
Journal of Neuro-Oncology 06/2011; 105(3):531-8. · 3.21 Impact Factor
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Bridget J McCarthy,
Kristin M Rankin,
Ken Aldape,
Melissa L Bondy,
Thomas Brännström,
Helle Broholm,
Maria Feychting,
Dora Il'yasova,
Peter D Inskip,
Christoffer Johansen, Beatrice S Melin,
Avima M Ruder,
Mary Ann Butler,
Michael E Scheurer,
Joachim Schüz,
Judith A Schwartzbaum,
Margaret R Wrensch,
Faith G Davis
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ABSTRACT: Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
Neuro-Oncology 02/2011; 13(2):242-50. · 5.72 Impact Factor
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ABSTRACT: In genome-wide association studies, inherited risk of glioma has been demonstrated for rare familial syndromes and with common variants from 3-5 chromosomal regions. To assess the degree of familial aggregation of glioma, the authors performed a pooled analysis of data from 2 large glioma case-control studies in the United States (MD Anderson Cancer Center, Houston, Texas (1994-2006) and University of California, San Francisco (1991-2004)) and from the Swedish Cancer Registry (1958-2006) to measure excess cases of cancer among first-degree relatives of glioma probands. This analysis included 20,377 probands with glioma and 52,714 first-degree relatives. No overall increase was found in the expected number of cancers among family members; however, there were 77% more gliomas than expected. There were also significantly more sarcoma and melanoma cases than expected, which is supported by evidence in the literature, whereas there were significantly fewer-than-expected cases of leukemia, non-Hodgkin lymphoma, and bladder, lung, pancreatic, prostate, and uterine cancers. This large pooled analysis provided sufficient numbers of related family members to examine the genetic mechanisms involved in the aggregation of glioma with other cancers in these families. However, misclassification due to unvalidated cancers among family members could account for the differences seen by study site.
American journal of epidemiology 11/2010; 172(10):1099-107. · 5.59 Impact Factor
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Dominique S Michaud,
Valentina Gallo,
Brigitte Schlehofer,
Anne Tjønneland,
Anja Olsen,
Kim Overvad,
Christina C Dahm,
Birgit Teucher,
Annekatrin Lukanova,
Heiner Boeing, [......], Beatrice S Melin,
Jonas Manjer,
Elisabet Wirfält,
Kay-Tee Khaw,
Nick Wareham,
Naomi E Allen,
Timothy J Key,
Isabelle Romieu,
Paolo Vineis,
Elio Riboli
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ABSTRACT: In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma.
The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC).
Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors.
We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant.
In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas.
American Journal of Clinical Nutrition 11/2010; 92(5):1145-50. · 6.67 Impact Factor
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Dominique S Michaud,
Valentina Gallo,
Brigitte Schlehofer,
Anne Tjønneland,
Anja Olsen,
Kim Overvad,
Christina C Dahm,
Rudolf Kaaks,
Annekatrin Lukanova,
Heiner Boeing, [......],
Jonas Manjer,
Signe Borgquist,
Kay-Tee Khaw,
Nick Wareham,
Naomi E Allen,
Konstantinos K Tsilidis,
Isabelle Romieu,
Sabina Rinaldi,
Paolo Vineis,
Elio Riboli
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ABSTRACT: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC).
After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI).
No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46).
Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation.
Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements.
Cancer Epidemiology Biomarkers & Prevention 10/2010; 19(10):2562-9. · 4.12 Impact Factor
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Lindsay B Robertson,
Georgina N Armstrong,
Bianca D Olver,
Amy L Lloyd,
Sanjay Shete,
Ching Lau,
Elizabeth B Claus,
Jill Barnholtz-Sloan,
Rose Lai,
Dora Il'yasova, [......],
Nicholas A Vick,
Christoffer Johansen,
Hanne Bødtcher,
Siegal Sadetzki,
Revital Bar-Sade Bruchim,
Galit Hirsh Yechezkel,
Ulrika Andersson, Beatrice S Melin,
Melissa L Bondy,
Richard S Houlston
Familial Cancer 06/2010; · 1.30 Impact Factor
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Lindsay B Robertson,
Georgina N Armstrong,
Bianca D Olver,
Amy L Lloyd,
Sanjay Shete,
Ching Lau,
Elizabeth B Claus,
Jill Barnholtz-Sloan,
Rose Lai,
Dora Il'yasova, [......],
Nicholas A Vick,
Christoffer Johansen,
Hanne Bødtcher,
Siegal Sadetzki,
Revital Bar-Sade Bruchim,
Galit Hirsh Yechezkel,
Ulrika Andersson, Beatrice S Melin,
Melissa L Bondy,
Richard S Houlston
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ABSTRACT: There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.
Familial Cancer 05/2010; 9(3):413-21. · 1.30 Impact Factor
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Yanhong Liu,
Sanjay Shete,
Carol J Etzel,
Michael Scheurer,
George Alexiou,
Georgina Armstrong,
Spyros Tsavachidis,
Fu-Wen Liang,
Mark Gilbert,
Ken Aldape,
Terri Armstrong,
Richard Houlston,
Fay Hosking,
Lindsay Robertson,
Yuanyuan Xiao,
John Wiencke,
Margaret Wrensch,
Ulrika Andersson, Beatrice S Melin,
Melissa Bondy
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ABSTRACT: Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment.
Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; <or= 12 months) and long-term survivors (LTS; >or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs.
We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years).
Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.
Journal of Clinical Oncology 04/2010; 28(14):2467-74. · 18.37 Impact Factor
