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1. Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Author

Sugier, P.E., Lucotte, E.A., Domenighetti, C., Law, M.H., Iles, M.M., Brown, K., Amos, C., McKay, J.D., Hung, R.J., Karimi, M., Bacq-Daian, D., Boland-Augé, A., Olaso, R., Deleuze, J.F., Lesueur, F., Ostroumova, E., Kesminiene, A., Vathaire, F. de, Guénel, P., Sreelatha, A.A.K., Schulte, C., Grover, S., May, P., Bobbili, D.R., Radivojkov-Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Koks, S., Taba, P., Lesage, S., Brice, A., Corvol, J.C., Chartier-Harlin, M.C., Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Nakayama, A., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y. J., Kolber, P., Warrenburg, B.P.C. van de, Bloem, B.R., Aasly, J., Toft, M., Pihlstrøm, L., Guedes, L.C., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez-Fairen, M., Wirdefeldt, K., Pedersen, N., Ran, C., Belin, A.C., Puschmann, A., Rödström, E.Y., Clarke, C.E., Morrison, K.E., Tan, M., Krainc, D., Burbulla, L.F., Farrer, M.J., Kruger, R., Gasser, T., Sharma, M., Truong, T., Elbaz, A., Sugier, P.E., Lucotte, E.A., Domenighetti, C., Law, M.H., Iles, M.M., Brown, K., Amos, C., McKay, J.D., Hung, R.J., Karimi, M., Bacq-Daian, D., Boland-Augé, A., Olaso, R., Deleuze, J.F., Lesueur, F., Ostroumova, E., Kesminiene, A., Vathaire, F. de, Guénel, P., Sreelatha, A.A.K., Schulte, C., Grover, S., May, P., Bobbili, D.R., Radivojkov-Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Koks, S., Taba, P., Lesage, S., Brice, A., Corvol, J.C., Chartier-Harlin, M.C., Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Nakayama, A., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y. J., Kolber, P., Warrenburg, B.P.C. van de, Bloem, B.R., Aasly, J., Toft, M., Pihlstrøm, L., Guedes, L.C., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez-Fairen, M., Wirdefeldt, K., Pedersen, N., Ran, C., Belin, A.C., Puschmann, A., Rödström, E.Y., Clarke, C.E., Morrison, K.E., Tan, M., Krainc, D., Burbulla, L.F., Farrer, M.J., Kruger, R., Gasser, T., Sharma, M., Truong, T., and Elbaz, A.

Abstract

Item does not contain fulltext, BACKGROUND: Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. OBJECTIVE: We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. METHODS: We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. RESULTS: We confirmed a previously reported positive genetic correlation of PD with melanoma (G(corr) = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G(corr) = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driv

Published
2023

3. Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity*.

Author

Laskar R., Ferreiro-Iglesias A., Kanetsky P.A., Law M.H., Goldstein A.M., Robbins H.A., Mann G.J., Cust A.E., Schmid H., Hopper J.L., Aitken J.F., Armstrong B.K., Giles G.G., Holland E., Kefford R.F., Jenkins M.A., Newton Bishop J.A., Affleck P., Barrett J.H., Bishop D.T., Harrison J., Iles M.M., Randerson-Moor J., Harland M., Taylor J.C., Whittaker L., Kukalizch K., Leake S., Karpavicius B., Haynes S., Mack T., Chan M., Taylor Y., Davies J., King P., Laskar R., Ferreiro-Iglesias A., Kanetsky P.A., Law M.H., Goldstein A.M., Robbins H.A., Mann G.J., Cust A.E., Schmid H., Hopper J.L., Aitken J.F., Armstrong B.K., Giles G.G., Holland E., Kefford R.F., Jenkins M.A., Newton Bishop J.A., Affleck P., Barrett J.H., Bishop D.T., Harrison J., Iles M.M., Randerson-Moor J., Harland M., Taylor J.C., Whittaker L., Kukalizch K., Leake S., Karpavicius B., Haynes S., Mack T., Chan M., Taylor Y., Davies J., and King P.

Abstract

Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. Objective(s): We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. Method(s): We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. Result(s): When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0.001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0.04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. Conclusion(s): We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.Copyright © 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Published
2021

4. Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

Author

Armstrong B.K., Laskar R., Ferreiro-Iglesias A., Kanetsky P.A., Law M.H., Goldstein A.M., Robbins H.A., Mann G.J., Cust A.E., Schmid H., Hopper J.L., Aitken J.F., Randerson-Moor J., Harland M., Taylor J.C., Whittaker L., Kukalizch K., Leake S., Karpavicius B., Haynes S., Mack T., Chan M., Taylor Y., Davies J., King P., Barrett J.H., Giles G.G., Holland E., Kefford R.F., Jenkins M.A., Newton Bishop J.A., Affleck P., Bishop D.T., Harrison J., Iles M.M., Armstrong B.K., Laskar R., Ferreiro-Iglesias A., Kanetsky P.A., Law M.H., Goldstein A.M., Robbins H.A., Mann G.J., Cust A.E., Schmid H., Hopper J.L., Aitken J.F., Randerson-Moor J., Harland M., Taylor J.C., Whittaker L., Kukalizch K., Leake S., Karpavicius B., Haynes S., Mack T., Chan M., Taylor Y., Davies J., King P., Barrett J.H., Giles G.G., Holland E., Kefford R.F., Jenkins M.A., Newton Bishop J.A., Affleck P., Bishop D.T., Harrison J., and Iles M.M.

Abstract

Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. Objective(s): We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. Method(s): We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. Result(s): When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0.001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0.04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. Conclusion(s): We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.Copyright © 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Published
2021

5. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Landi, M.T. Bishop, D.T. MacGregor, S. Machiela, M.J. Stratigos, A.J. Ghiorzo, P. Brossard, M. Calista, D. Choi, J. Fargnoli, M.C. Zhang, T. Rodolfo, M. Trower, A.J. Menin, C. Martinez, J. Hadjisavvas, A. Song, L. Stefanaki, I. Scolyer, R. Yang, R. Goldstein, A.M. Potrony, M. Kypreou, K.P. Pastorino, L. Queirolo, P. Pellegrini, C. Cattaneo, L. Zawistowski, M. Gimenez-Xavier, P. Rodriguez, A. Elefanti, L. Manoukian, S. Rivoltini, L. Smith, B.H. Loizidou, M.A. Del Regno, L. Massi, D. Mandala, M. Khosrotehrani, K. Akslen, L.A. Amos, C.I. Andresen, P.A. Avril, M.-F. Azizi, E. Soyer, H.P. Bataille, V. Dalmasso, B. Bowdler, L.M. Burdon, K.P. Chen, W.V. Codd, V. Craig, J.E. Dębniak, T. Falchi, M. Fang, S. Friedman, E. Simi, S. Galan, P. Garcia-Casado, Z. Gillanders, E.M. Gordon, S. Green, A. Gruis, N.A. Hansson, J. Harland, M. Harris, J. Helsing, P. Henders, A. Hočevar, M. Höiom, V. Hunter, D. Ingvar, C. Kumar, R. Lang, J. Lathrop, G.M. Lee, J.E. Li, X. Lubiński, J. Mackie, R.M. Malt, M. Malvehy, J. McAloney, K. Mohamdi, H. Molven, A. Moses, E.K. Neale, R.E. Novaković, S. Nyholt, D.R. Olsson, H. Orr, N. Fritsche, L.G. Puig-Butille, J.A. Qureshi, A.A. Radford-Smith, G.L. Randerson-Moor, J. Requena, C. Rowe, C. Samani, N.J. Sanna, M. Schadendorf, D. Schulze, H.-J. Simms, L.A. Smithers, M. Song, F. Swerdlow, A.J. van der Stoep, N. Kukutsch, N.A. Visconti, A. Wallace, L. Ward, S.V. Wheeler, L. Sturm, R.A. Hutchinson, A. Jones, K. Malasky, M. Vogt, A. Zhou, W. Pooley, K.A. Elder, D.E. Han, J. Hicks, B. Hayward, N.K. Kanetsky, P.A. Brummett, C. Montgomery, G.W. Olsen, C.M. Hayward, C. Dunning, A.M. Martin, N.G. Evangelou, E. Mann, G.J. Long, G. Pharoah, P.D.P. Easton, D.F. Barrett, J.H. Cust, A.E. Abecasis, G. Duffy, D.L. Whiteman, D.C. Gogas, H. De Nicolo, A. Tucker, M.A. Newton-Bishop, J.A. Peris, K. Chanock, S.J. Demenais, F. Brown, K.M. Puig, S. Nagore, E. Shi, J. Iles, M.M. Law, M.H. GenoMEL Consortium Q-MEGA QTWIN Investigators ATHENS Melanoma Study Group 23andMe The SDH Study Group IBD Investigators Essen-Heidelberg Investigators AMFS Investigators MelaNostrum Consortium

Abstract

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2020

6. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Author

Houlston R., Choudhury P.P., Easton D.F., Milne R.L., Simard J., Hall P., Michailidou K., Dennis J., Schmidt M.K., Chang-Claude J., Gharahkhani P., Whiteman D., O'Mara T.A., Spurdle A.B., Thompson D.J., Tomlinson I., De Vivo I., Campbell P.T., Hoffmeister M., Jenkins M., Peters U., Hsu L., Gruber S.B., Casey G., Schmit S.L., Landi M.T., Law M.H., Iles M.M., Demenais F., Kumar R., MacGregor S., Bishop D.T., Ward S.V., Bondy M.L., Wiencke J.K., Melin B., Barnholtz-Sloan J., Kinnersley B., Wrensch M.R., Hung R.J., Caporaso N.E., Berndt S.I., Birmann B.M., Camp N.J., Kraft P., Rothman N., Slager S.L., Berchuck A., Pharoah P.D.P., Sellers T.A., Gayther S.A., Pearce C.L., Goode E.L., Schildkraut J.M., Moysich K.B., Amos C.I., Brennan P., McKay J., Amundadottir L.T., Jacobs E.J., Klein A.P., Petersen G.M., Risch H.A., Stolzenberg-Solomon R.Z., Wolpin B.M., Li D., Eeles R.A., Haiman C.A., Kote-Jarai Z., Schumacher F.R., Al Olama A.A., Purdue M.P., Scelo G., Dalgaard M.D., Greene M.H., Grotmol T., Kanetsky P.A., McGlynn K.A., Nathanson K.L., Turnbull C., Wiklund F., Chanock S.J., Chatterjee N., Garcia-Closas M., Zhang Y.D., Hurson A.N., Zhang H., Houlston R., Choudhury P.P., Easton D.F., Milne R.L., Simard J., Hall P., Michailidou K., Dennis J., Schmidt M.K., Chang-Claude J., Gharahkhani P., Whiteman D., O'Mara T.A., Spurdle A.B., Thompson D.J., Tomlinson I., De Vivo I., Campbell P.T., Hoffmeister M., Jenkins M., Peters U., Hsu L., Gruber S.B., Casey G., Schmit S.L., Landi M.T., Law M.H., Iles M.M., Demenais F., Kumar R., MacGregor S., Bishop D.T., Ward S.V., Bondy M.L., Wiencke J.K., Melin B., Barnholtz-Sloan J., Kinnersley B., Wrensch M.R., Hung R.J., Caporaso N.E., Berndt S.I., Birmann B.M., Camp N.J., Kraft P., Rothman N., Slager S.L., Berchuck A., Pharoah P.D.P., Sellers T.A., Gayther S.A., Pearce C.L., Goode E.L., Schildkraut J.M., Moysich K.B., Amos C.I., Brennan P., McKay J., Amundadottir L.T., Jacobs E.J., Klein A.P., Petersen G.M., Risch H.A., Stolzenberg-Solomon R.Z., Wolpin B.M., Li D., Eeles R.A., Haiman C.A., Kote-Jarai Z., Schumacher F.R., Al Olama A.A., Purdue M.P., Scelo G., Dalgaard M.D., Greene M.H., Grotmol T., Kanetsky P.A., McGlynn K.A., Nathanson K.L., Turnbull C., Wiklund F., Chanock S.J., Chatterjee N., Garcia-Closas M., Zhang Y.D., Hurson A.N., and Zhang H.

Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.Copyright © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2020

8. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways (vol 9, 4774, 2018)

Author

Duffy, D.L., Zhu, G., Li, X., Sanna, M., Iles, M.M., Jacobs, L.C., Evans, D.M., Yazar, S., Beesley, J., Law, M.H., Kraft, P., Visconti, A., Taylor, J.C., Liu, F., Wright, M.J., Henders, A.K., Bowdler, L., Glass, D., Ikram, M.A., Uitterlinden, A.G., Madden, P.A., Heath, A.C., Nelson, E.C., Green, A.C., Chanock, S., Barrett, J.H., Brown, M.A., Hayward, N.K., MacGregor, S., Sturm, R.A., Hewitt, A.W., Kayser, M., Hunter, D.J., Bishop, J.A.N., Spector, T.D., Montgomery, G.W., Mackey, D.A., Smith, G.D., Nijsten, T.E., Bishop, D.T., Bataille, V., Falchi, M., Han, J., Martin, N.G., Lee, J.E., Brossard, M., Moses, E.K., Song, F., Kumar, R., Easton, D.F., Pharoah, P.D.P., Swerdlow, A.J., Kypreou, K.P., Harland, M., Randerson-Moor, J., Akslen, L.A., Andresen, P.A., Avril, M.F., Azizi, E., Scarra, G.B., Brown, K.M., Debniak, T., Elder, D.E., Fang, S.Y., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E.M., Goldstein, A.M., Gruis, N.A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Ingvar, C., Kanetsky, P.A., Chen, W.V., Landi, M.T., Lang, J., Lathrop, G.M., Lubinski, J., Mackie, R.M., Mann, G.J., Molven, A., Novakovic, S., Olsson, H., Puig, S., Puig-Butille, J.A., Radford-Smith, G.L., Stoep, N. van der, Doorn, R. van, Whiteman, D.C., Craig, J.E., Schadendorf, D., Simms, L.A., Burdon, K.P., Nyholt, D.R., Pooley, K.A., Orr, N., Stratigos, A.J., Cust, A.E., Ward, S.V., Schulze, H.J., Dunning, A.M., Demenais, F., Amos, C.I., and Melanoma GWAS Consortium

Published
2019

10. Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

Author

Laskar, R., Ferreiro‐Iglesias, A., Bishop, D.T., Iles, M.M., Kanetsky, P.A., Armstrong, B.K., Law, M.H., Goldstein, A.M., Aitken, J.F., Giles, G.G., Robbins, H.A., and Cust, A.E.

Subjects
MELANOMA, ULTRAVIOLET radiation, HETEROGENEITY, SKIN examination, NECK, RADIATION exposure, LOGISTIC regression analysis
Abstract

Summary: Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. Objectives: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. Methods: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population‐based case–control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway‐specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. Results: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P‐heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P‐heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. Conclusions: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices. What is already known about this topic?Two main biological pathways have been proposed for the aetiology of melanoma – determined by naevi and type of sun exposure and related to the anatomical site at which melanoma develops.Risk factors for melanoma may differ by anatomical site, but analyses are often limited by study sample size and most have focused on sun exposure. What does this study add?This study provides an examination of a comprehensive set of risk factors for melanoma by anatomical site, using a harmonized dataset from two population‐based studies with 3592 participants.The presence of increased numbers of naevi was more strongly associated with melanomas on the trunk and limbs than on the head and neck.Very fair skin was more weakly related to melanoma on the trunk than on other sites.The association of pathway‐specific polygenic risk scores with melanoma did not differ by anatomical site. Linked Comment: Ghiasvand. Br J Dermatol 2021; 184:995–996. [ABSTRACT FROM AUTHOR]

Published
2021
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11. Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure

Author

Visconti, A. (Alessia), Duffy, D.L. (David), Liu, F. (Fan), Zhu, G. (Gu), Wu, W. (Wenting), Yan, C. (Chen), Hysi, P.G. (Pirro), Zeng, C. (Changqing), Sanna, M. (Marianna), Iles, M.M. (Mark M.), Kanetsky, P.P. (Peter P.), Demenais, F. (Florence), Hamer, M.A. (Merel), Uitterlinden, A.G. (André), Ikram, M.A. (Arfan), Nijsten, T.E.C. (Tamar), Martin, N.G. (Nicholas), Kayser, M.H. (Manfred), Spector, T.D. (Timothy), Han, J. (Jiali), Bataille, V. (Veronique), Falchi, M. (Mario), Visconti, A. (Alessia), Duffy, D.L. (David), Liu, F. (Fan), Zhu, G. (Gu), Wu, W. (Wenting), Yan, C. (Chen), Hysi, P.G. (Pirro), Zeng, C. (Changqing), Sanna, M. (Marianna), Iles, M.M. (Mark M.), Kanetsky, P.P. (Peter P.), Demenais, F. (Florence), Hamer, M.A. (Merel), Uitterlinden, A.G. (André), Ikram, M.A. (Arfan), Nijsten, T.E.C. (Tamar), Martin, N.G. (Nicholas), Kayser, M.H. (Manfred), Spector, T.D. (Timothy), Han, J. (Jiali), Bataille, V. (Veronique), and Falchi, M. (Mario)

Abstract

The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant associat

Published
2018
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12. Does polygenic risk influence associations between sun exposure and melanoma? A prospective cohort analysis.

Author

Olsen, C.M., Pandeya, N., Law, M.H., MacGregor, S., Iles, M.M., Thompson, B.S., Green, A.C., Neale, R.E., and Whiteman, D.C.

Subjects
COHORT analysis, GENOTYPE-environment interaction, MELANOMA, BIRTHPLACES, SKIN aging, ULTRAVIOLET radiation, CYCLIN-dependent kinase inhibitor-2A
Abstract

Summary: Background: Melanoma develops as the result of complex interactions between sun exposure and genetic factors. However, data on these interactions from prospective studies are scant. Objectives: To quantify the association between ambient and personal ultraviolet exposure and incident melanoma in a large population‐based prospective study of men and women residing in a setting of high ambient ultraviolet radiation, and to examine potential gene–environment interactions. Methods: Data were obtained from the QSkin Sun and Health Study, a prospective cohort study of men and women aged 40–69 years, randomly sampled from the Queensland population in 2011. Participants were genotyped and assessed for ultraviolet exposure. Results: Among participants with genetic data (n = 15 373), 420 (2·7%) developed cutaneous melanoma (173 invasive, 247 in situ) during a median follow‐up time of 4·4 years. Country of birth, age at migration, having > 50 sunburns in childhood or adolescence, and a history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk. Conclusions: An interaction with polygenic risk was suggested: among people at low polygenic risk, markers of cumulative sun exposure (as measured by actinic damage) were associated with melanoma. In contrast, among people at high polygenic risk, markers of high‐level early‐life ambient exposure (as measured by place of birth) were associated with melanoma (hazard ratio for born in Australia vs. overseas 3·16, 95% confidence interval 1·39–7·22). These findings suggest interactions between genotype and environment that are consistent with divergent pathways for melanoma development. What's already known about this topic? The relationship between sun exposure and melanoma is complex, and exposure effects are highly modified by host factors and behaviours.The role of genotype on the relationship between ultraviolet radiation exposure and melanoma risk is poorly understood. What does this study add? We found that country of birth, age at migration, sunburns in childhood or adolescence, and history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk, while other measures of continuous or more intermittent patterns of sun exposure were not.We found evidence for gene–environment interactions that are consistent with divergent pathways for melanoma development. Linked Comment: Cust. Br J Dermatol 2020; 183:205–206. Plain language summary available online [ABSTRACT FROM AUTHOR]

Published
2020
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13. Is there a causal relationship between vitamin D and melanoma risk? A Mendelian randomization study.

Author

Liyanage, U.E., Law, M.H., Barrett, J.H., Iles, M.M., and MacGregor, S.

Subjects
VITAMIN D, MELANOMA, VITAMIN D deficiency, SINGLE nucleotide polymorphisms, ONLINE comments
Abstract

Summary: Background: Several preclinical studies have identified the antiproliferative effects of 25‐hydroxyvitamin D [25(OH)D; vitamin D]. Ultraviolet radiation (UVR) is essential for vitamin D synthesis yet increases the risk of melanoma. Observational studies on the association of vitamin D levels with melanoma risk have reported inconclusive results, and are difficult to interpret owing to the potential confounding from the dual role of UVR. Objectives: To determine whether there is a causal association between genetically predicted 25(OH)D concentrations and melanoma using a Mendelian randomization (MR) approach. Methods: We performed MR using summary data from a large genome‐wide association study (GWAS) meta‐analysis of melanoma risk, consisting of 12 874 cases and 23 203 controls. Five single nucleotide polymorphisms associated with 25(OH)D concentration – rs12785878, rs10741657, rs2282679, rs6013897 and rs116970203 – were selected as instrumental variables. An inverse variance weighted method was used to access the evidence for causality. MR results from the melanoma meta‐analysis were combined with results from an MR study based on a melanoma risk GWAS using UK Biobank data. Results: A 20 nmol L−1 decrease in 25(OH)D was not associated with melanoma risk [odds ratio (OR) 1·06, 95% confidence interval (CI) 0·95–1·19]. Results from the UK Biobank were concordant with this, with meta‐analysis of our and UK Biobank‐derived MR causal estimates showing no association (OR 1·02, 95% CI 0·92–1·13 for a 20 nmol L−1 decrease). Conclusions: The results suggest that vitamin D levels may not be causally associated with the risk of melanoma. What's already known about this topic? Antitumour activity of vitamin D has been identified in preclinical studies.Observational studies link vitamin D deficiency with an increased risk of a range of cancers.There is a growing public interest for vitamin D supplementation.Observational studies of melanoma are fraught with difficulties because while higher ultraviolet radiation levels increase vitamin D levels, such exposure is also associated with increased melanoma risk.Results from observational studies are inconclusive regarding the effect of vitamin D on melanoma risk. What does this study add? Using Mendelian randomization, an approach to causal inference, which is analogous to a natural randomized controlled trial, we found no causal association between vitamin D levels and melanoma. Plain language summary available online Linked Comment: Bell. Br J Dermatol 2020; 182:13–14. [ABSTRACT FROM AUTHOR]

Published
2020
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14. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

Author

Haycock, P.C., Burgess, S., Nounu, A., Zheng, J., Okoli, G.N., Bowden, J., Wade, K.H., Timpson, N.J., Evans, D.M., Willeit, P., Aviv, A., Gaunt, T.R., Hemani, G., Mangino, M., Ellis, H.P., Kurian, K.M., Pooley, K.A., Eeles, R.A., Lee, J.E., Fang, S., Chen, W.V., Law, M.H., Bowdler, L.M., Iles, M.M., Yang, Q., Worrall, B.B., Markus, H.S., Hung, R.J., Amos, C.I., Spurdle, A.B., Thompson, D.J., O'Mara, T.A., Wolpin, B., Amundadottir, L., Stolzenberg-Solomon, R., Trichopoulou, A., Onland-Moret, N.C., Lund, E., Duell, E.J., Canzian, F., Severi, G., Overvad, K., Gunter, M.J., Tumino, R., Svenson, U., Rij, A. van, Baas, A.F., Bown, M.J., Samani, N.J., t'Hof, F.N.G. van, Tromp, G., Jones, G.T., Kuivaniemi, H., Elmore, J.R., Johansson, M., McKay, J., Scelo, G., Carreras-Torres, R., Gaborieau, V., Brennan, P., Bracci, P.M., Neale, R.E., Olson, S.H., Gallinger, S., Li, D., Petersen, G.M., Risch, H.A., Klein, A.P., Han, J., Abnet, C.C., Freedman, N.D., Taylor, P.R., Maris, J.M., Aben, K.K.H., Kiemeney, L.A., Vermeulen, S.H., Wiencke, J.K., Walsh, K.M., Wrensch, M., Rice, T., Turnbull, C., Litchfield, K., Paternoster, L., Standl, M., Abecasis, G.R., SanGiovanni, J.P., Li, Y., Mijatovic, V., Sapkota, Y., Low, S.K., Zondervan, K.T., Montgomery, G.W., Nyholt, D.R., Heel, D.A. van, Hunt, K., Arking, D.E., Ashar, F.N., Sotoodehnia, N., Woo, D., et al., Haycock, P.C., Burgess, S., Nounu, A., Zheng, J., Okoli, G.N., Bowden, J., Wade, K.H., Timpson, N.J., Evans, D.M., Willeit, P., Aviv, A., Gaunt, T.R., Hemani, G., Mangino, M., Ellis, H.P., Kurian, K.M., Pooley, K.A., Eeles, R.A., Lee, J.E., Fang, S., Chen, W.V., Law, M.H., Bowdler, L.M., Iles, M.M., Yang, Q., Worrall, B.B., Markus, H.S., Hung, R.J., Amos, C.I., Spurdle, A.B., Thompson, D.J., O'Mara, T.A., Wolpin, B., Amundadottir, L., Stolzenberg-Solomon, R., Trichopoulou, A., Onland-Moret, N.C., Lund, E., Duell, E.J., Canzian, F., Severi, G., Overvad, K., Gunter, M.J., Tumino, R., Svenson, U., Rij, A. van, Baas, A.F., Bown, M.J., Samani, N.J., t'Hof, F.N.G. van, Tromp, G., Jones, G.T., Kuivaniemi, H., Elmore, J.R., Johansson, M., McKay, J., Scelo, G., Carreras-Torres, R., Gaborieau, V., Brennan, P., Bracci, P.M., Neale, R.E., Olson, S.H., Gallinger, S., Li, D., Petersen, G.M., Risch, H.A., Klein, A.P., Han, J., Abnet, C.C., Freedman, N.D., Taylor, P.R., Maris, J.M., Aben, K.K.H., Kiemeney, L.A., Vermeulen, S.H., Wiencke, J.K., Walsh, K.M., Wrensch, M., Rice, T., Turnbull, C., Litchfield, K., Paternoster, L., Standl, M., Abecasis, G.R., SanGiovanni, J.P., Li, Y., Mijatovic, V., Sapkota, Y., Low, S.K., Zondervan, K.T., Montgomery, G.W., Nyholt, D.R., Heel, D.A. van, Hunt, K., Arking, D.E., Ashar, F.N., Sotoodehnia, N., Woo, D., and et al.

Abstract

Contains fulltext : 174181.pdf (publisher's version ) (Closed access), Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420081 cases (median cases, 2526 per disease) and 1093105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cance

Published
2017

15. A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte growth via regulation of MITF

Author

Choi, J.Y., Xu, M., Makowski, M.M., Zhang, T.W., Law, M.H., Kovacs, M.A., Granzhan, A., Kim, W.D.J., Parikh, H., Gartside, M., Trent, J.M., Teulade-Fichou, M.P., Iles, M.M., Newton-Bishop, J.A., Bishop, D.T., MacGregor, S., Hayward, N.K., Vermeulen, M., Brown, K.M., Choi, J.Y., Xu, M., Makowski, M.M., Zhang, T.W., Law, M.H., Kovacs, M.A., Granzhan, A., Kim, W.D.J., Parikh, H., Gartside, M., Trent, J.M., Teulade-Fichou, M.P., Iles, M.M., Newton-Bishop, J.A., Bishop, D.T., MacGregor, S., Hayward, N.K., Vermeulen, M., and Brown, K.M.

Abstract

Contains fulltext : 177722.pdf (publisher's version ) (Closed access)

Published
2017

16. Association between telomere length and risk of cancer and non-neoplastic diseases a mendelian randomization study

Author

Haycock, P. (Philip), Burgess, S. (Stephen), Nounu, A. (Aayah), Zheng, J. (Jie), Okoli, G.N. (George N.), Bowden, J., Wade, K.H. (Kaitlin Hazel), Timpson, N.J. (Nicholas J.), Evans, D.M. (David M.), Willeit, P. (Peter), Aviv, A. (Abraham), Gaunt, T.R. (Tom), Hemani, G., Mangino, M. (Massimo), Ellis, H.P. (Hayley Patricia), Kurian, K.M. (Kathreena M.), Pooley, K.A. (Karen A.), Eeles, R. (Rosalind), Lee, J.E. (Jeffrey E.), Fang, S. (Shenying), Chen, W.V. (Wei V.), Law, M.H. (Matthew H.), Bowdler, L.M. (Lisa M.), Iles, M.M. (Mark M.), Yang, Q. (Qiong Fang), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh), Hung, R.J. (Rayjean J.), Amos, W., Spurdle, A.B. (Amanda), Thompson, D. (Deborah), O'Mara, T.A. (Tracy A.), Wolpin, B. (Brian), Amundadottir, L. (Laufey), Stolzenberg-Solomon, R. (Rachael), Trichopoulou, A. (Antonia), Onland-Moret, N.C. (Charlotte), Lund, E. (Eiliv), Duell, E.J. (Eric), Canzian, F. (Federico), Severi, G. (Gianluca), Overvad, K. (Kim), Gunter, M.J. (Marc J.), Tumino, R. (Rosario), Svenson, U. (Ulrika), Rij, A.M. (Andre) van, Baas, A.F. (Annette), Bown, N., Samani, N.J. (Nilesh), Van t'Hof, F.N.G. (Femke N.G.), Tromp, G. (Gerard), Jones, G.T. (Gregory T.), Kuivaniemi, H. (Helena), Elmore, J.R. (James R.), Johansson, M. (Mattias), Mckay, J. (James), Scelo, G. (Ghislaine), Carreras-Torres, R. (Robert), Gaborieau, V. (Valerie), Brennan, P. (Paul), Bracci, P.M. (Paige M.), Neale, R.E. (Rachel E.), Olson, S.H. (Sara H.), Gallinger, S. (Steve), Li, D. (Donghui), Olson, S.H. (Sara), Risch, H. (Harvey), Klein, A.P. (Alison P.), Han, J., Abnet, C.C. (Christian C.), Freedman, N.D. (Neal D.), Taylor, P.R. (Phil R.), Maris, J.M. (John), Aben, K.K.H. (Katja), Kiemeney, L.A.L.M. (Bart), Vermeulen, S.H.H.M. (Sita), Wiencke, J.K. (John K.), Walsh, K.M. (Kyle M.), Wrensch, M. (Margaret), Rice, T. (Terri), Turnbull, C. (Clare), Litchfield, K. (Kevin), Paternoster, L. (Lavinia), Standl, M. (Marie), Abecasis, G.R. (Gonçalo), SanGiovanni, J.P. (John Paul), Li, Y. (Yong), Mijatovic, V. (Vladan), Sapkota, Y. (Yadav), Low, S.-K. (Siew-Kee), Zondervan, K.T. (Krina), Montgomery, G.W. (Grant W.), Nyholt, D.R. (Dale), Heel, D.A. (David) van, Hunt, K. (Karen), Arking, D.E. (Dan), Ashar, F.N. (Foram N.), Sotoodehnia, N. (Nona), Woo, D. (Daniel), Rosand, J. (Jonathan), Comeau, M.E. (Mary E.), Brown, W.M. (W. Mark), Silverman, E. (Edwin), Hokanson, J.E. (John E.), Cho, M.H. (Michael), Hui, J. (Jennie), Ferreira, M.A. (Manuel A.), Thompson, P.J. (Philip J.), Morrison, A.C. (Alanna), Felix, J.F. (Janine F.), Smith, N.L. (Nicholas L.), Christiano, A.M. (Angela), Petukhova, L. (Lynn), Betz, R.C. (Regina), Fan, X. (Xing), Zhang, X. (Xuejun), Zhu, C. (Caihong), Langefeld, C.D. (Carl), Thompson, S.D. (Susan D.), Wang, F. (Feijie), Lin, X. (Xu), Schwartz, D.A. (David A.), Fingerlin, T.E. (Tasha E.), Rotter, J.I. (Jerome I.), Cotch, M.F. (Mary Frances), Jensen, R.A. (Richard A.), Munz, M. (Matthias), Dommisch, H. (Henrik), Schaefer, A. (Antje), Han, F. (Fang), Ollila, H.M., Hillary, R.P. (Ryan P.), Albagha, O.M.E. (Omar M.), Ralston, S.H. (Stuart), Zeng, C. (Chenjie), Zheng, W. (Wei), Shu, X.-O. (Xiao-Ou), Reis, A. (André), Uebe, S. (Steffen), Hüffmeier, U. (Ulrike), Kawamura, Y. (Yoshiya), Otowa, T. (Takeshi), Sasaki, T. (Tsukasa), Hibberd, M.L. (Martin), Davila, S. (Sonia), Xie, G. (Gang), Siminovitch, K.A. (Katherine), Bei, J.-X. (Jin-Xin), Zeng, Y.X., Försti, A. (Asta), Chen, B. (Bowang), Landi, S. (Stefano), Franke, A. (Andre), Fischer, A. (Annegret), Ellinghaus, D. (David), Flores, C. (Carlos), Noth, I. (Imre), Ma, S.-F. (Shwu-Fan), Foo, J.-N. (Jia-Nee), Liu, J. (Jianjun), Kim, J.-W. (Jong-Won), Cox, D.G. (David), Delattre, O. (Olivier), Mirabeau, O. (Olivier), Skibola, C.F. (Christine F.), Tang, C.S. (Clara S.), Garcia-Barcelo, M., Chang, K.-P. (Kai-Ping), Su, W.-H. (Wen-Hui), Chang, Y.-S. (Yu-Sun), Martin, N.G. (Nicholas G.), Gordon, S.D. (Scott D.), Wade, T.D. (Tracey D.), Lee, C. (Chaeyoung), Kubo, M. (Michiaki), Cha, P.-C. (Pei-Chieng), Nakamura, Y. (Yusuke), Levy, D. (Daniel), Kimura, M. (Masayuki), Hwang, S.-J. (Shih-Jen), Hunt, S.C. (Steven), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Manichaikul, A.W. (Ani W.), Barr, R.G. (Graham), Kahali, B. (Bratati), Speliotes, E.K. (Elizabeth), Yerges-Armstrong, L.M. (Laura), Cheng, C-Y. (Ching-Yu), Jonas, J.B. (Jost B.), Wong, T.Y. (Tien Yin), Fogh, I. (Isabella), Lin, K. (Kuang), Powell, J. (John), Rice, K. (Kenneth), Relton, C.L. (Caroline), Martin, R.M. (Richard M.), Smith, A.V. (Davey), Haycock, P. (Philip), Burgess, S. (Stephen), Nounu, A. (Aayah), Zheng, J. (Jie), Okoli, G.N. (George N.), Bowden, J., Wade, K.H. (Kaitlin Hazel), Timpson, N.J. (Nicholas J.), Evans, D.M. (David M.), Willeit, P. (Peter), Aviv, A. (Abraham), Gaunt, T.R. (Tom), Hemani, G., Mangino, M. (Massimo), Ellis, H.P. (Hayley Patricia), Kurian, K.M. (Kathreena M.), Pooley, K.A. (Karen A.), Eeles, R. (Rosalind), Lee, J.E. (Jeffrey E.), Fang, S. (Shenying), Chen, W.V. (Wei V.), Law, M.H. (Matthew H.), Bowdler, L.M. (Lisa M.), Iles, M.M. (Mark M.), Yang, Q. (Qiong Fang), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh), Hung, R.J. (Rayjean J.), Amos, W., Spurdle, A.B. (Amanda), Thompson, D. (Deborah), O'Mara, T.A. (Tracy A.), Wolpin, B. (Brian), Amundadottir, L. (Laufey), Stolzenberg-Solomon, R. (Rachael), Trichopoulou, A. (Antonia), Onland-Moret, N.C. (Charlotte), Lund, E. (Eiliv), Duell, E.J. (Eric), Canzian, F. (Federico), Severi, G. (Gianluca), Overvad, K. (Kim), Gunter, M.J. (Marc J.), Tumino, R. (Rosario), Svenson, U. (Ulrika), Rij, A.M. (Andre) van, Baas, A.F. (Annette), Bown, N., Samani, N.J. (Nilesh), Van t'Hof, F.N.G. (Femke N.G.), Tromp, G. (Gerard), Jones, G.T. (Gregory T.), Kuivaniemi, H. (Helena), Elmore, J.R. (James R.), Johansson, M. (Mattias), Mckay, J. (James), Scelo, G. (Ghislaine), Carreras-Torres, R. (Robert), Gaborieau, V. (Valerie), Brennan, P. (Paul), Bracci, P.M. (Paige M.), Neale, R.E. (Rachel E.), Olson, S.H. (Sara H.), Gallinger, S. (Steve), Li, D. (Donghui), Olson, S.H. (Sara), Risch, H. (Harvey), Klein, A.P. (Alison P.), Han, J., Abnet, C.C. (Christian C.), Freedman, N.D. (Neal D.), Taylor, P.R. (Phil R.), Maris, J.M. (John), Aben, K.K.H. (Katja), Kiemeney, L.A.L.M. (Bart), Vermeulen, S.H.H.M. (Sita), Wiencke, J.K. (John K.), Walsh, K.M. (Kyle M.), Wrensch, M. (Margaret), Rice, T. (Terri), Turnbull, C. (Clare), Litchfield, K. (Kevin), Paternoster, L. (Lavinia), Standl, M. (Marie), Abecasis, G.R. (Gonçalo), SanGiovanni, J.P. (John Paul), Li, Y. (Yong), Mijatovic, V. (Vladan), Sapkota, Y. (Yadav), Low, S.-K. (Siew-Kee), Zondervan, K.T. (Krina), Montgomery, G.W. (Grant W.), Nyholt, D.R. (Dale), Heel, D.A. (David) van, Hunt, K. (Karen), Arking, D.E. (Dan), Ashar, F.N. (Foram N.), Sotoodehnia, N. (Nona), Woo, D. (Daniel), Rosand, J. (Jonathan), Comeau, M.E. (Mary E.), Brown, W.M. (W. Mark), Silverman, E. (Edwin), Hokanson, J.E. (John E.), Cho, M.H. (Michael), Hui, J. (Jennie), Ferreira, M.A. (Manuel A.), Thompson, P.J. (Philip J.), Morrison, A.C. (Alanna), Felix, J.F. (Janine F.), Smith, N.L. (Nicholas L.), Christiano, A.M. (Angela), Petukhova, L. (Lynn), Betz, R.C. (Regina), Fan, X. (Xing), Zhang, X. (Xuejun), Zhu, C. (Caihong), Langefeld, C.D. (Carl), Thompson, S.D. (Susan D.), Wang, F. (Feijie), Lin, X. (Xu), Schwartz, D.A. (David A.), Fingerlin, T.E. (Tasha E.), Rotter, J.I. (Jerome I.), Cotch, M.F. (Mary Frances), Jensen, R.A. (Richard A.), Munz, M. (Matthias), Dommisch, H. (Henrik), Schaefer, A. (Antje), Han, F. (Fang), Ollila, H.M., Hillary, R.P. (Ryan P.), Albagha, O.M.E. (Omar M.), Ralston, S.H. (Stuart), Zeng, C. (Chenjie), Zheng, W. (Wei), Shu, X.-O. (Xiao-Ou), Reis, A. (André), Uebe, S. (Steffen), Hüffmeier, U. (Ulrike), Kawamura, Y. (Yoshiya), Otowa, T. (Takeshi), Sasaki, T. (Tsukasa), Hibberd, M.L. (Martin), Davila, S. (Sonia), Xie, G. (Gang), Siminovitch, K.A. (Katherine), Bei, J.-X. (Jin-Xin), Zeng, Y.X., Försti, A. (Asta), Chen, B. (Bowang), Landi, S. (Stefano), Franke, A. (Andre), Fischer, A. (Annegret), Ellinghaus, D. (David), Flores, C. (Carlos), Noth, I. (Imre), Ma, S.-F. (Shwu-Fan), Foo, J.-N. (Jia-Nee), Liu, J. (Jianjun), Kim, J.-W. (Jong-Won), Cox, D.G. (David), Delattre, O. (Olivier), Mirabeau, O. (Olivier), Skibola, C.F. (Christine F.), Tang, C.S. (Clara S.), Garcia-Barcelo, M., Chang, K.-P. (Kai-Ping), Su, W.-H. (Wen-Hui), Chang, Y.-S. (Yu-Sun), Martin, N.G. (Nicholas G.), Gordon, S.D. (Scott D.), Wade, T.D. (Tracey D.), Lee, C. (Chaeyoung), Kubo, M. (Michiaki), Cha, P.-C. (Pei-Chieng), Nakamura, Y. (Yusuke), Levy, D. (Daniel), Kimura, M. (Masayuki), Hwang, S.-J. (Shih-Jen), Hunt, S.C. (Steven), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Manichaikul, A.W. (Ani W.), Barr, R.G. (Graham), Kahali, B. (Bratati), Speliotes, E.K. (Elizabeth), Yerges-Armstrong, L.M. (Laura), Cheng, C-Y. (Ching-Yu), Jonas, J.B. (Jost B.), Wong, T.Y. (Tien Yin), Fogh, I. (Isabella), Lin, K. (Kuang), Powell, J. (John), Rice, K. (Kenneth), Relton, C.L. (Caroline), Martin, R.M. (Richard M.), and Smith, A.V. (Davey)

Abstract

IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer ca

Published
2017
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17. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Author

Fang, J. (Jun), Jia, J. (Jinping), Makowski, M. (Matthew), Xu, M. (Mai), Wang, Z. (Zhaoming), Zhang, T. (Tongwu), Hoskins, J.W. (Jason W.), Choi, J. (Jiyeon), Han, Y. (Younghun), Zhang, M. (Mingfeng), Thomas, J. (Janelle), Kovacs, M. (Michael), Collins, I. (Irene), Dzyadyk, M. (Marta), Thompson, A. (Abbey), O'Neill, M. (Maura), Das, S. (Sudipto), Lan, Q. (Qi), Koster, R. (Roelof), Stolzenberg-Solomon, R.S. (Rachael S.), Kraft, P. (Peter), Wolpin, B.M. (Brian M.), Jansen, P., Olson, S. (Sara), McGlynn, K.A., Kanetsky, P.P. (Peter P.), Chatterjee, N. (Nilanjan), Barrett, J.H. (Jennifer H.), Dunning, A.M. (Alison), Taylor, J.C. (John C.), Newton Bishop, J.A. (Julia), Timothy Bishop, D. (D.), Andresson, T. (Thorkell), Petersen, G.M. (Gloria M.), Amos, W., Iles, M.M. (Mark M.), Nathanson, K.L. (Katherine), Landi, M.T. (Maria Teresa), Vermeulen, M. (Michiel), Brown, K.M. (Kevin M.), Amundadottir, L.T. (Laufey T.), Fang, J. (Jun), Jia, J. (Jinping), Makowski, M. (Matthew), Xu, M. (Mai), Wang, Z. (Zhaoming), Zhang, T. (Tongwu), Hoskins, J.W. (Jason W.), Choi, J. (Jiyeon), Han, Y. (Younghun), Zhang, M. (Mingfeng), Thomas, J. (Janelle), Kovacs, M. (Michael), Collins, I. (Irene), Dzyadyk, M. (Marta), Thompson, A. (Abbey), O'Neill, M. (Maura), Das, S. (Sudipto), Lan, Q. (Qi), Koster, R. (Roelof), Stolzenberg-Solomon, R.S. (Rachael S.), Kraft, P. (Peter), Wolpin, B.M. (Brian M.), Jansen, P., Olson, S. (Sara), McGlynn, K.A., Kanetsky, P.P. (Peter P.), Chatterjee, N. (Nilanjan), Barrett, J.H. (Jennifer H.), Dunning, A.M. (Alison), Taylor, J.C. (John C.), Newton Bishop, J.A. (Julia), Timothy Bishop, D. (D.), Andresson, T. (Thorkell), Petersen, G.M. (Gloria M.), Amos, W., Iles, M.M. (Mark M.), Nathanson, K.L. (Katherine), Landi, M.T. (Maria Teresa), Vermeulen, M. (Michiel), Brown, K.M. (Kevin M.), and Amundadottir, L.T. (Laufey T.)

Abstract

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365- C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.

Published
2017
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18. Association between putative functional variants in the PSMB9 gene and risk of melanoma re-analysis of published melanoma genome-wide association studies

Author

Qian, J., Liu, H.L., Wei, S., Liu, Z.S., Li, Y.K., Wang, L.E., Chen, W.V., Amos, C.I., Lee, J.E., Iles, M.M., Law, M.H., Cust, A.E., Barrett, J.H., Montgomery, G.W., Taylor, J., Bishop, J.A.N., MacGregor, S., Bishop, D.T., Mann, G.J., Hayward, N.K., Wei, Q.Y., GenoMEL Investigators, and Q-MEGA AMFS Investigators

Subjects
PSMB9, Molecular Sequence Data, Single-nucleotide polymorphism, Genome-wide association study, Dermatology, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, polymorphism, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, medicine, melanoma, SNP, Humans, Genetic Predisposition to Disease, RNA, Messenger, Promoter Regions, Genetic, Gene, 030304 developmental biology, Genetics, 0303 health sciences, genome-wide association study, Base Sequence, Melanoma, Publications, Case-control study, Australia, Reproducibility of Results, medicine.disease, 3. Good health, Gene Expression Regulation, Neoplastic, Cysteine Endopeptidases, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, cell cycle
Abstract

To mine possibly hidden causal single nucleotide polymorphisms (SNPs) in the etiology of melanoma, we investigated the association of SNPs in 76 M/G1 transition genes with melanoma risk using our published genome-wide association study (GWAS) dataset with 1804 melanoma cases and 1,026 cancer-free controls. We found multiple SNPs with P < 0.01 and performed validation studies for 18 putative functional SNPs in PSMB9 in other two GWAS datasets. Two SNPs (rs1351383 and rs2127675) were associated with melanoma risk in the GenoMEL dataset (P = 0.013 and 0.004, respectively), but failed validation in the Australia dataset. Genotype-phenotype analysis revealed these two SNPs were significantly correlated with mRNA expression levels of PSMB9. Further experiments revealed that the promoter SNP rs2071480, which is in high LD with rs1351383 and rs2127675, involved in influencing transcription factor binding and gene expression. Taken together, our data suggested that functional variants in PSMB9 may contribute to melanoma susceptibility.

Published
2013

20. Genome-wide association study identifies three new melanoma susceptibility loci

Author

Barrett, J.H., Iles, M.M., Harland, M., Taylor, J.C., Aitken, J.F., Andresen, P.A., Akslen, L.A., Armstrong, B.K., Avril, M.F., Azizi, E., Bakker, B., Bergman, W., Bianchi-Scarra, G., Bressac-de Paillerets, B., Calista, D., Cannon-Albright, L.A., Corda, E., Cust, A.E., Debniak, T., Duffy, D., Dunning, A.M., Easton, D.F., Friedman, E., Galan, P., Ghiorzo, P., Giles, G.G., Hansson, J., Hocevar, M., Hoiom, V., Hopper, J.L., Ingvar, C., Janssen, B., Jenkins, M.A., Jonsson, G., Kefford, R.F., Landi, G., Landi, M.T., Lang, J., Lubinski, J., Mackie, R., Malvehy, J., Martin, N.G., Molven, A., Montgomery, G.W., Nieuwpoort, F.A. van, Novakovic, S., Olsson, H., Pastorino, L., Puig, S., Puig-Butille, J.A., Randerson-Moor, J., Snowden, H., Tuominen, R., VanBelle, P., Stoep, N. van der, Whiteman, D.C., Zelenika, D., Han, J.L., Fang, S.Y., Lee, J.E., Wei, Q.Y., Lathrop, G.M., Gillanders, E.M., Brown, K.M., Goldstein, A.M., Kanetsky, P.A., Mann, G.J., MacGregor, S., Elder, D.E., Amos, C.I., Hayward, N.K., Gruis, N.A., Demenais, F., Bishop, J.A.N., Bishop, D.T., and GenoMEL Consortium

Published
2011

21. Genome-wide association study identifies three loci associated with melanoma risk

Author

Bishop, D.T., Demenais, F., Iles, M.M., Harland, M., Taylor, J.C., Corda, E., Randerson-Moor, J., Aitken, J.F, Avril, M.-F., Azizi, E., Bakker, B., Bianchi-Scarrà, G., Bressac-de Paillerets, B., Calista, D., Cannon-Albright, L.A., Chin-A-Woeng, T., Dębniak, T., Galore-Haskel, G., Ghiorzo, P., Gut, I., Hansson, J., Hočevar, M., Höiom, V., Hopper, J.L., Ingvar, C., Kanetsky, P.A., Kefford, R.F., Landi, M.T., Lang, J., Lubiński, J., Mackie, R., Malvehy, J., Mann, G.J., Martin, N.G., Montgomery, G.W., van Nieuwpoort, F.A., Novakovic, S., Olsson, H., Puig, S., Weiss, M., van Workum, W., Zelenika, D., Brown, K.M., Goldstein, A.M., Gillanders, E.M., Boland, A., Galan, P., Elder, D.E., Gruis, N.A., Hayward, N.K., Lathrop, G.M., Barrett, J.H., and Newton Bishop, J.A.

Subjects
RC0254
Abstract

We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 times 10-7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 times 10-27 for rs258322), 11q14-q21 encompassing TYR (P = 2.41 times 10-14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 times 10-7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.

Published
2009

22. Genomewide association analysis of coronary artery disease

Author

Samani, N.J., Erdmann, J., Hall, A.S., Hengstenberg, C., Mangino, M., Mayer, B., Dixon, R.J., Meitinger, T., Braund, P., Wichmann, H.-E., Barrett, J.H., König, I.R., Stevens, S.E., Szymczak, S., Tregouet, D.A., Iles, M.M., Pahlke, F., Pollard, H., Lieb, W., Cambien, F., Fischer, M., Ouwehand, W., Blankenberg, S., Balmforth, AJ., Baessler, A., Ball, S.G., Strom, T.M., Braenne, I., Gieger, C., Deloukas, P., Tobin, M.D., Ziegler, A., Thompson, J.R., Schunkert, H., Wellcome Trust Case Consortium (WTCCC) (), and CARDIOGENICS Consortium ()

Abstract

Modern genotyping platforms permit a systematic search for inherited components of complex diseases. We performed a joint analysis of two genomewide association studies of coronary artery disease. METHODS: We first identified chromosomal loci that were strongly associated with coronary artery disease in the Wellcome Trust Case Control Consortium (WTCCC) study (which involved 1926 case subjects with coronary artery disease and 2938 controls) and looked for replication in the German MI [Myocardial Infarction] Family Study (which involved 875 case subjects with myocardial infarction and 1644 controls). Data on other single-nucleotide polymorphisms (SNPs) that were significantly associated with coronary artery disease in either study (P80%) of a true association: chromosomes 1p13.3 (rs599839), 1q41 (rs17465637), 10q11.21 (rs501120), and 15q22.33 (rs17228212). CONCLUSIONS: We identified several genetic loci that, individually and in aggregate, substantially affect the risk of development of coronary artery disease.

Published
2007

23. A variant in FTO shows association with melanoma risk not due to BMI

Author

Iles, M.M., Law, M.H., Stacey, S.N., Han, J., Fang, S., Pfeiffer, R., Harland, M., MacGregor, S., Taylor, J.C., Aben, K.K.H., Akslen, L.A., Avril, M.F., Azizi, E., Bakker, B., Benediktsdottir, K.R., Bergman, W., Scarra, G.B., Brown, K.M., Calista, D., Chaudru, V., Fargnoli, M.C., Cust, A.E., Demenais, F., Waal, A.C. de, Debniak, T., Elder, D.E., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E.M., Goldstein, A.M., Gruis, N.A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Hopper, J.L., Ingvar, C., Janssen, M., Jenkins, M.A., Kanetsky, P.A., Kiemeney, L.A.L.M., Lang, J., Lathrop, G.M., Leachman, S., Lee, J.E., Lubinski, J., Mackie, R.M., Mann, G.J., Martin, N.G., Mayordomo, J.I., Molven, A., Mulder, S., Nagore, E., Novakovic, S., Okamoto, I., Olafsson, J.H., Olsson, H., Pehamberger, H., Peris, K., Grasa, M.P., Planelles, D., Puig, S., Puig-Butille, J.A., Randerson-Moor, J., Requena, C., Rivoltini, L., Rodolfo, M., Santinami, M., Sigurgeirsson, B., Snowden, H., Song, F., Sulem, P., Thorisdottir, K., Tuominen, R., Belle, P. Van, Stoep, N. van der, Rossum, M.M. van, Wei, Q., Wendt, J., Zelenika, D., Zhang, M., Landi, M.T., Thorleifsson, G., Bishop, D.T., Amos, C.I., Hayward, N.K., Stefansson, K., Bishop, J.A., Barrett, J.H., et al., Iles, M.M., Law, M.H., Stacey, S.N., Han, J., Fang, S., Pfeiffer, R., Harland, M., MacGregor, S., Taylor, J.C., Aben, K.K.H., Akslen, L.A., Avril, M.F., Azizi, E., Bakker, B., Benediktsdottir, K.R., Bergman, W., Scarra, G.B., Brown, K.M., Calista, D., Chaudru, V., Fargnoli, M.C., Cust, A.E., Demenais, F., Waal, A.C. de, Debniak, T., Elder, D.E., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E.M., Goldstein, A.M., Gruis, N.A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Hopper, J.L., Ingvar, C., Janssen, M., Jenkins, M.A., Kanetsky, P.A., Kiemeney, L.A.L.M., Lang, J., Lathrop, G.M., Leachman, S., Lee, J.E., Lubinski, J., Mackie, R.M., Mann, G.J., Martin, N.G., Mayordomo, J.I., Molven, A., Mulder, S., Nagore, E., Novakovic, S., Okamoto, I., Olafsson, J.H., Olsson, H., Pehamberger, H., Peris, K., Grasa, M.P., Planelles, D., Puig, S., Puig-Butille, J.A., Randerson-Moor, J., Requena, C., Rivoltini, L., Rodolfo, M., Santinami, M., Sigurgeirsson, B., Snowden, H., Song, F., Sulem, P., Thorisdottir, K., Tuominen, R., Belle, P. Van, Stoep, N. van der, Rossum, M.M. van, Wei, Q., Wendt, J., Zelenika, D., Zhang, M., Landi, M.T., Thorleifsson, G., Bishop, D.T., Amos, C.I., Hayward, N.K., Stefansson, K., Bishop, J.A., Barrett, J.H., and et al.

Abstract

Contains fulltext : 118658.pdf (publisher's version ) (Closed access), We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.

Published
2013

24. Assessment of melanoma candidate genes in a meta‐analysis of 16 534 melanoma cases.

Author

Ntritsos, G., Dimou, N., Kypreou, K., Stefanaki, I., Loizidou, M.A., Hadjisavvas, A., Kyriacou, K., MacGregor, S., Law, M.H., Iles, M.M., Stratigos, A.J., and Evangelou, E.

Subjects
MELANOMA, META-analysis, GENES, GENETIC databases, SKIN cancer
Abstract

Assessment of melanoma candidate genes in a meta-analysis of 16 534 melanoma cases Cutaneous melanoma (CM) accounts for the majority of deaths from skin cancer and its development is an interplay between phenotypic characteristics,[1] environmental exposures[2] and genetic risk factors.[3] Several genetic variants have been found to be strongly associated with risk of melanoma using a candidate gene approach. GLO:3NZ/01oct19:jdv15662-fig-0001.jpg PHOTO (COLOR): Summary of the GWAS meta-analysis and three replication studies for the association of one SNP in Lymphotoxin Alpha gene with cutaneous melanoma. gl. [Extracted from the article]

Published
2019
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25. 维生素 D 水平能否影响您的黑色素瘤风险?

Author

Liyanage, U.E., Law, M.H., Barrett, J.H., Iles, M.M., and MacGregor, S.

Subjects
RESEARCH
Abstract

Summary: 黑色素瘤是一种最致命的皮肤癌形式。根据澳大利亚癌症数据库统计数据, 2018 年, 黑色素瘤的发生率(意指病例数量)为 14778 例, 死亡人数为 1684 例。 在医学文献(如期刊)中关于维生素 D 可能对黑色素瘤风险发挥的作用存在很大争议。有些研究将维生素 D 缺乏症(意指维生素 D 水平较低)与许多不同癌症的风险增加相关联。 对黑色素瘤的研究充满困难, 这是因为虽然阳光中较高的紫外线辐射 (UVR) 水平使体内维生素 D 水平增加,但 UVR 暴露也会增加黑色素瘤的风险。 在本项目中, 作者旨在确定维生素 D 水平是否会影响黑色素瘤风险。他们进行了孟德尔随机化分析 (MR),这是一种分析不同基因变体的方法,其可用于确定因果关系(原因和效果)。这项研究使用了欧洲血统基因数据,并结合将遗传标志物与维生素 D 水平相关联的数据。 作者表明, 即使预测的维生素 D 水平变化很大(20 nmol/L 下降),也仅对黑色素瘤风险产生轻微影响。虽然有些研究表明, 改变维生素 D 水平可能会降低黑色素瘤风险, 但这项研究未提供证据证明, 基因确定的维生素 D 与黑色素瘤风险存在因果关系(相关联)。 This summary relates to the study: 维生素 D 与黑色素瘤风险之间是否存在因果关系?一项孟德尔随机化分析研究。 Linked Article: Liyanage et al. Br J Dermatol 2020; 182:97–103 [ABSTRACT FROM AUTHOR]

Published
2020
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26. Can vitamin D levels affect your risk of melanoma?

Author

Liyanage, U.E., Law, M.H., Barrett, J.H., Iles, M.M., and MacGregor, S.

Subjects
VITAMIN D, MELANOMA, VITAMIN D deficiency, SUNBURN, SKIN cancer, NUMERIC databases, GENETIC markers, BRAF genes
Abstract

Summary: Melanoma, the most lethal form of skin cancer. According to Australian cancer database statistics, the incidence (meaning number of cases) of melanoma in 2018 was 14,778 and the number of deaths was 1,684. There is considerable debate in the medical literature (e.g. journals) on the role that vitamin D may play in melanoma risk. Some studies link vitamin D deficiency, meaning lower levels of vitamin D, with an increased risk of a range of different cancers. Studies into melanoma are fraught with difficulties because while higher ultraviolet radiation levels (UVR) from the sun increase the body's vitamin D levels, UVR exposure can also increase the risk of melanoma. In this project, the authors aimed to determine if vitamin D levels can affect melanoma risk. They performed Mendelian randomization (MR), a way of analysing different variants of genes that can be used to determine causality (cause and effect). The study used European ancestry genetic data, together with data linking genetic markers to vitamin D levels. The authors showed that even large predicted changes in vitamin D levels (a 20 nmol/L decrease), only negligibly affected melanoma risk. Whilst some studies have suggested that modifying vitamin D levels may reduce melanoma risk, this study provides no evidence that genetically determined vitamin D is causally associated (linked) with melanoma risk. This summary relates to the study: Is there a causal relationship between vitamin D and melanoma risk? A Mendelian randomization study Linked Article: Liyanage et al. Br J Dermatol 2020; 182:97–103 [ABSTRACT FROM AUTHOR]

Published
2020
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