Pleiotropic and sex-specific effects of cancer GWAS SNPs on melanoma risk in the Population Architecture using Genomics and Epidemiology (PAGE) study. Kocarnik, J. M., Park, S. L., Han, J., Dumitrescu, L., Cheng, I., Wilkens, L. R., Schumacher, F. R., Kolonel, L., Carlson, C. S., Crawford, D. C., Goodloe, R. J., Dilks, H. H., Baker, P., Richardson, D., Matise, T. C., Ambite, J. L., Song, F., Qureshi, A. A., Zhang, M., Duggan, D., Hutter, C., Hindorff, L., Bush, W. S., Kooperberg, C., Le Marchand, L., & Peters, U. PloS one, 10:e0120491, 2015. ![Pleiotropic and sex-specific effects of cancer GWAS SNPs on melanoma risk in the Population Architecture using Genomics and Epidemiology (PAGE) study. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes.
@article{KocarnikParkHanEtAl2015,
abstract = {Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the {Population Architecture using Genomics and Epidemiology} (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This {SNP} is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes.},
author = {Kocarnik, Jonathan M. and Park, S. Lani and Han, Jiali and Dumitrescu, Logan and Cheng, Iona and Wilkens, Lynne R. and Schumacher, Fredrick R. and Kolonel, Laurence and Carlson, Chris S. and Crawford, Dana C. and Goodloe, Robert J. and Dilks, Holli H. and Baker, Paxton and Richardson, Danielle and Matise, Tara C. and Ambite, Jos{\'e} Luis and Song, Fengju and Qureshi, Abrar A. and Zhang, Mingfeng and Duggan, David and Hutter, Carolyn and Hindorff, Lucia and Bush, William S. and Kooperberg, Charles and Le Marchand, Loic and Peters, Ulrike},
chemicals = {CLPTM1L protein, human, Membrane Proteins, Neoplasm Proteins, TERT protein, human, Telomerase},
citation-subset = {IM},
completed = {2015-12-15},
country = {United States},
doi = {10.1371/journal.pone.0120491},
issn = {1932-6203},
issn-linking = {1932-6203},
issue = {3},
journal = {PloS one},
keywords = {Aged; Aged, 80 and over; Alleles; Case-Control Studies; Female; Genetic Pleiotropy; Genome-Wide Association Study; Genotype; Humans; Lung Neoplasms, genetics, pathology; Male; Melanoma, genetics, pathology; Membrane Proteins, genetics; Metagenomics; Middle Aged; Neoplasm Proteins, genetics; Polymorphism, Single Nucleotide; Prostatic Neoplasms, genetics, pathology; Risk; Sex Factors; Skin Neoplasms, genetics, metabolism; Telomerase, genetics},
nlm-id = {101285081},
owner = {NLM},
pages = {e0120491},
pii = {PONE-D-14-45087},
pmc = {PMC4366224},
pmid = {25789475},
url = {https://pubmed.ncbi.nlm.nih.gov/25789475/},
pubmodel = {Electronic-eCollection},
pubstate = {epublish},
revised = {2018-11-13},
title = {Pleiotropic and sex-specific effects of cancer {GWAS} {SNP}s on melanoma risk in the {Population Architecture using Genomics and Epidemiology} ({PAGE}) study.},
volume = {10},
year = {2015},
bdsk-url-1 = {https://pubmed.ncbi.nlm.nih.gov/25789475/},
bdsk-url-2 = {https://doi.org/10.1371/journal.pone.0120491}}
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We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. 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