Genome-Wide Association Studies of Multiple Keratinocyte Cancers.
There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs...
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doaj-705d1067632243c5ad01bc2b30bfc1c82020-11-25T01:45:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016987310.1371/journal.pone.0169873Genome-Wide Association Studies of Multiple Keratinocyte Cancers.Luba M PardoWen-Qing LiShih-Jen HwangJoris A C VerkouterenAlbert HofmanAndré G UitterlindenPeter KraftConstance TurmanJiali HanEunyoung ChoJoanne M MurabitoDaniel LevyAbrar A QureshiTamar NijstenThere is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene.http://europepmc.org/articles/PMC5231365?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luba M Pardo Wen-Qing Li Shih-Jen Hwang Joris A C Verkouteren Albert Hofman André G Uitterlinden Peter Kraft Constance Turman Jiali Han Eunyoung Cho Joanne M Murabito Daniel Levy Abrar A Qureshi Tamar Nijsten |
spellingShingle |
Luba M Pardo Wen-Qing Li Shih-Jen Hwang Joris A C Verkouteren Albert Hofman André G Uitterlinden Peter Kraft Constance Turman Jiali Han Eunyoung Cho Joanne M Murabito Daniel Levy Abrar A Qureshi Tamar Nijsten Genome-Wide Association Studies of Multiple Keratinocyte Cancers. PLoS ONE |
author_facet |
Luba M Pardo Wen-Qing Li Shih-Jen Hwang Joris A C Verkouteren Albert Hofman André G Uitterlinden Peter Kraft Constance Turman Jiali Han Eunyoung Cho Joanne M Murabito Daniel Levy Abrar A Qureshi Tamar Nijsten |
author_sort |
Luba M Pardo |
title |
Genome-Wide Association Studies of Multiple Keratinocyte Cancers. |
title_short |
Genome-Wide Association Studies of Multiple Keratinocyte Cancers. |
title_full |
Genome-Wide Association Studies of Multiple Keratinocyte Cancers. |
title_fullStr |
Genome-Wide Association Studies of Multiple Keratinocyte Cancers. |
title_full_unstemmed |
Genome-Wide Association Studies of Multiple Keratinocyte Cancers. |
title_sort |
genome-wide association studies of multiple keratinocyte cancers. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene. |
url |
http://europepmc.org/articles/PMC5231365?pdf=render |
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