Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

被引：11

作者：

Bonilla, Carolina ^{[1
,2
]}

Bertoni, Bernardo ^{[3
]}

Min, Josine L. ^{[2
,4
]}

Hemani, Gibran ^{[2
,4
]}

Elliott, Hannah R. ^{[2
,4
]}

机构：

[1] Univ Sao Paulo, Fac Med, Dept Med Prevent, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP, Brazil

[2] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[3] Univ Republica, Fac Med, Dept Genet, Montevideo, Uruguay

[4] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

来源：

PIGMENT CELL & MELANOMA RESEARCH | 2021年 / 34卷 / 05期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

ALSPAC; ASIP; DNA methylation; GoDMC; MC1R; pigmentation; skin cancer; EXPRESSION; MC1R; RISK;

D O I：

10.1111/pcmr.12948

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.

引用

页码：892 / 904

页数：14

共 38 条

[21] Disentangling molecular relationships with a causal inference test [J].

Millstein, Joshua ;

Zhang, Bin ;

Zhu, Jun ;

Schadt, Eric E. .

BMC GENETICS, 2009, 10

[22] Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability [J].

Morgan, Michael D. ;

Pairo-Castineira, Erola ;

Rawlik, Konrad ;

Canela-Xandri, Oriol ;

Rees, Jonathan ;

Sims, David ;

Tenesa, Albert ;

Jackson, Ian J. .

NATURE COMMUNICATIONS, 2018, 9

[23] MC1R, Eumelanin and Pheomelanin: Their Role in Determining the Susceptibility to Skin Cancer [J].

Nasti, Tahseen H. ;

Timares, Laura .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2015, 91 (01) :188-200

[24] Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer [J].

Nikolouzakis, Taxiarchis Konstantinos ;

Falzone, Luca ;

Lasithiotakis, Konstantinos ;

Kruger-Krasagakis, Sabine ;

Kalogeraki, Alexandra ;

Sifaki, Maria ;

Spandidos, Demetrios A. ;

Chrysos, Emmanuel ;

Tsatsakis, Aristidis ;

Tsiaoussis, John .

JOURNAL OF CLINICAL MEDICINE, 2020, 9 (09) :1-21

[25] Genetic evidence for the convergent evolution of light skin in Europeans and east Asians [J].

Norton, Heather L. ;

Kittles, Rick A. ;

Parra, Esteban ;

McKeigue, Paul ;

Mao, Xianyun ;

Cheng, Keith ;

Canfield, Victor A. ;

Bradley, Daniel G. ;

McEvoy, Brian ;

Shriver, Mark D. .

MOLECULAR BIOLOGY AND EVOLUTION, 2007, 24 (03) :710-722

[26] The Genetics of Human Skin and Hair Pigmentation [J].

Pavan, William J. ;

Sturm, Richard A. .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 20, 2019, 2019, 20 :41-72

[27] Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms [J].

Pierce, Brandon L. ;

Tong, Lin ;

Argos, Maria ;

Demanelis, Kathryn ;

Jasmine, Farzana ;

Rakibuz-Zaman, Muhammad ;

Sarwar, Golam ;

Islam, Md. Tariqul ;

Shahriar, Hasan ;

Islam, Tariqul ;

Rahman, Mahfuzar ;

Yunus, Md. ;

Kibriya, Muhammad G. ;

Chen, Lin S. ;

Ahsan, Habibul .

NATURE COMMUNICATIONS, 2018, 9

[28] Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood [J].

Qi, Ting ;

Wu, Yang ;

Zeng, Jian ;

Zhang, Futao ;

Xue, Angli ;

Jiang, Longda ;

Zhu, Zhihong ;

Kemper, Kathryn ;

Yengo, Loic ;

Zheng, Zhili ;

Marioni, Riccardo E. ;

Montgomery, Grant W. ;

Deary, Ian J. ;

Wray, Naomi R. ;

Visscher, Peter M. ;

McRae, Allan F. ;

Yang, Jian .

NATURE COMMUNICATIONS, 2018, 9

[29] Shades of complexity: New perspectives on the evolution and genetic architecture of human skin [J].

Quillen, Ellen E. ;

Norton, Heather L. ;

Parra, Esteban J. ;

Lona-Durazo, Frida ;

Ang, Khai C. ;

Mircea Illiescu, Florin ;

Pearson, Laurel N. ;

Shriver, Mark D. ;

Lasisi, Tina ;

Gokcumen, Omer ;

Starr, Izzy ;

Lin, Yen-Lung ;

Martin, Alicia R. ;

Jablonski, Nina G. .

AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, 2019, 168 :4-26

[30] Non Melanoma Skin Cancer and Subsequent Cancer Risk [J].

Rees, Judy R. ;

Zens, M. Scot ;

Gui, Jiang ;

Celaya, Maria O. ;

Riddle, Bruce L. ;

Karagas, Margaret R. .

PLOS ONE, 2014, 9 (06)

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