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The effect on melanoma risk of genes previously associated with telomere length.

Iles MM, Bishop DT, Taylor JC, Hayward NK, Brossard M, Cust AE, Dunning AM, Lee JE, Moses EK, Akslen LA, AMFS InvestigatorsAndresen PA, Avril MF, Azizi E, Scarrà GB, Brown KM, Dębniak T, Elder DE, Friedman E, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Harland M, Helsing P, Hočevar M, Höiom V, IBD investigatorsIngvar C, Kanetsky PA, Landi MT, Lang J, Lathrop GM, Lubiński J, Mackie RM, Martin NG, Molven A, Montgomery GW, Novaković S, Olsson H, Puig S, Puig-Butille JA, QMEGA and QTWIN InvestigatorsRadford-Smith GL, Randerson-Moor J, SDH Study Groupvan der Stoep N, van Doorn R, Whiteman DC, MacGregor S, Pooley KA, Ward SV, Mann GJ, Amos CI, Pharoah PD, Demenais F, Law MH, Newton Bishop JA, Barrett JH, GenoMEL Consorti - J. Natl. Cancer Inst. (2014)

Bottom Line: Telomere length has been associated with risk of many cancers, but results are inconsistent.A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk.This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality.

View Article: PubMed Central - PubMed

Affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK (MMI, DTB, JCT, MHa, JRM, JANB, JHB); Oncogenomics (NKH), Genetic Epidemiology (NGM), Inflammatory Bowel Diseases Laboratory (GLRS), Cancer Control Group (DCW), Statistical Genetics (SM, MHL), and Molecular Epidemiology (GWM), QIMR Berghofer Medical Research Institute, Brisbane, Australia; INSERM, UMR-946, Genetic Variation and Human Diseases Unit, Paris, France (MB, FD); Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France (MB, FD); Cancer Epidemiology and Services Research, Sydney School of Public Health, University of Sydney, Australia (AEC); Department of Oncology, University of Cambridge, Cambridge, UK (AMD, PDPP); Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (JEL); Centre for Genetic Origins of Health and Disease, Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley, Australia (EKM, SVW); Centre for Cancer Biomarkers CCBIO (LAA) and Gade Laboratory for Pathology (AM), Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway (LAA); Department of Pathology, Molecular Pathology (PAA) and Department of Dermatology (PH), Oslo University Hospital, Rikshospitalet, Oslo, Norway; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Dermatologie, Université Paris Descartes, Paris, France (MFA); Department of Dermatology (EA) and Oncogenics Unit (EA, EF), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel (EA); Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy (GBS, EFPG); Laboratory of Genetics of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy (GBS, EFPG); Division of Cancer Epidemiology and Gene

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Forest plot of estimated effect size (with a 95% confidence interval indicated by horizontal bars) for telomere score on melanoma risk in nine geographic regions (and combined result). The relative sample size of each group is indicated by the size of the squares. Exact effect sizes (betas from SNPTEST2) are given in the right hand column.
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Figure 1: Forest plot of estimated effect size (with a 95% confidence interval indicated by horizontal bars) for telomere score on melanoma risk in nine geographic regions (and combined result). The relative sample size of each group is indicated by the size of the squares. Exact effect sizes (betas from SNPTEST2) are given in the right hand column.

Mentions: We found a strong association between increased telomere score and increased risk of melanoma (P = 8.92×10−9) that was consistent across geographic regions (Figure 1). Categorizing telomere score into quartiles, we observed a linear effect on melanoma risk; those in the highest quartile are estimated to be at 1.29 times the risk of melanoma of those in the lowest quartile (Supplementary Figure 3, available online).


The effect on melanoma risk of genes previously associated with telomere length.

Iles MM, Bishop DT, Taylor JC, Hayward NK, Brossard M, Cust AE, Dunning AM, Lee JE, Moses EK, Akslen LA, AMFS InvestigatorsAndresen PA, Avril MF, Azizi E, Scarrà GB, Brown KM, Dębniak T, Elder DE, Friedman E, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Harland M, Helsing P, Hočevar M, Höiom V, IBD investigatorsIngvar C, Kanetsky PA, Landi MT, Lang J, Lathrop GM, Lubiński J, Mackie RM, Martin NG, Molven A, Montgomery GW, Novaković S, Olsson H, Puig S, Puig-Butille JA, QMEGA and QTWIN InvestigatorsRadford-Smith GL, Randerson-Moor J, SDH Study Groupvan der Stoep N, van Doorn R, Whiteman DC, MacGregor S, Pooley KA, Ward SV, Mann GJ, Amos CI, Pharoah PD, Demenais F, Law MH, Newton Bishop JA, Barrett JH, GenoMEL Consorti - J. Natl. Cancer Inst. (2014)

Forest plot of estimated effect size (with a 95% confidence interval indicated by horizontal bars) for telomere score on melanoma risk in nine geographic regions (and combined result). The relative sample size of each group is indicated by the size of the squares. Exact effect sizes (betas from SNPTEST2) are given in the right hand column.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4196080&req=5

Figure 1: Forest plot of estimated effect size (with a 95% confidence interval indicated by horizontal bars) for telomere score on melanoma risk in nine geographic regions (and combined result). The relative sample size of each group is indicated by the size of the squares. Exact effect sizes (betas from SNPTEST2) are given in the right hand column.
Mentions: We found a strong association between increased telomere score and increased risk of melanoma (P = 8.92×10−9) that was consistent across geographic regions (Figure 1). Categorizing telomere score into quartiles, we observed a linear effect on melanoma risk; those in the highest quartile are estimated to be at 1.29 times the risk of melanoma of those in the lowest quartile (Supplementary Figure 3, available online).

Bottom Line: Telomere length has been associated with risk of many cancers, but results are inconsistent.A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk.This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality.

View Article: PubMed Central - PubMed

Affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK (MMI, DTB, JCT, MHa, JRM, JANB, JHB); Oncogenomics (NKH), Genetic Epidemiology (NGM), Inflammatory Bowel Diseases Laboratory (GLRS), Cancer Control Group (DCW), Statistical Genetics (SM, MHL), and Molecular Epidemiology (GWM), QIMR Berghofer Medical Research Institute, Brisbane, Australia; INSERM, UMR-946, Genetic Variation and Human Diseases Unit, Paris, France (MB, FD); Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France (MB, FD); Cancer Epidemiology and Services Research, Sydney School of Public Health, University of Sydney, Australia (AEC); Department of Oncology, University of Cambridge, Cambridge, UK (AMD, PDPP); Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (JEL); Centre for Genetic Origins of Health and Disease, Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley, Australia (EKM, SVW); Centre for Cancer Biomarkers CCBIO (LAA) and Gade Laboratory for Pathology (AM), Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway (LAA); Department of Pathology, Molecular Pathology (PAA) and Department of Dermatology (PH), Oslo University Hospital, Rikshospitalet, Oslo, Norway; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Dermatologie, Université Paris Descartes, Paris, France (MFA); Department of Dermatology (EA) and Oncogenics Unit (EA, EF), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel (EA); Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy (GBS, EFPG); Laboratory of Genetics of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy (GBS, EFPG); Division of Cancer Epidemiology and Gene

Show MeSH
Related in: MedlinePlus