Genome-wide association studies of multiple keratinocyte cancers

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 genomewide 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 (pvalue ≤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 (pvalue = 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.

Original languageEnglish (US)
Article numbere0169873
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Genome-Wide Association Study
keratinocytes
Polymorphism
Keratinocytes
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genes
neoplasms
Neoplasms
Health
nurses
Nurses
genome-wide association study
Chromosomes, Human, Pair 9
genes
Neoplasm Genes
Basal Cell Carcinoma
Genetic Association Studies
health care workers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pardo, L. M., Li, W. Q., Hwang, S. J., Verkouteren, J. A. C., Hofman, A., Uitterlinden, A. G., ... Nijsten, T. (2017). Genome-wide association studies of multiple keratinocyte cancers. PLoS One, 12(1), [e0169873]. https://doi.org/10.1371/journal.pone.0169873

Genome-wide association studies of multiple keratinocyte cancers. / Pardo, Luba M.; Li, Wen Qing; Hwang, Shih Jen; Verkouteren, Joris A.C.; Hofman, Albert; Uitterlinden, André G.; Kraft, Peter; Turman, Constance; Han, Jiali; Cho, Eunyoung; Murabito, Joanne M.; Levy, Daniel; Qureshi, Abrar A.; Nijsten, Tamar.

In: PLoS One, Vol. 12, No. 1, e0169873, 01.01.2017.

Research output: Contribution to journalArticle

Pardo, LM, Li, WQ, Hwang, SJ, Verkouteren, JAC, Hofman, A, Uitterlinden, AG, Kraft, P, Turman, C, Han, J, Cho, E, Murabito, JM, Levy, D, Qureshi, AA & Nijsten, T 2017, 'Genome-wide association studies of multiple keratinocyte cancers', PLoS One, vol. 12, no. 1, e0169873. https://doi.org/10.1371/journal.pone.0169873
Pardo LM, Li WQ, Hwang SJ, Verkouteren JAC, Hofman A, Uitterlinden AG et al. Genome-wide association studies of multiple keratinocyte cancers. PLoS One. 2017 Jan 1;12(1). e0169873. https://doi.org/10.1371/journal.pone.0169873
Pardo, Luba M. ; Li, Wen Qing ; Hwang, Shih Jen ; Verkouteren, Joris A.C. ; Hofman, Albert ; Uitterlinden, André G. ; Kraft, Peter ; Turman, Constance ; Han, Jiali ; Cho, Eunyoung ; Murabito, Joanne M. ; Levy, Daniel ; Qureshi, Abrar A. ; Nijsten, Tamar. / Genome-wide association studies of multiple keratinocyte cancers. In: PLoS One. 2017 ; Vol. 12, No. 1.
@article{c352798788b44465b638ad4073b2a427,
title = "Genome-wide association studies of multiple keratinocyte cancers",
abstract = "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 genomewide 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 (pvalue ≤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 (pvalue = 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.",
author = "Pardo, {Luba M.} and Li, {Wen Qing} and Hwang, {Shih Jen} and Verkouteren, {Joris A.C.} and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and Peter Kraft and Constance Turman and Jiali Han and Eunyoung Cho and Murabito, {Joanne M.} and Daniel Levy and Qureshi, {Abrar A.} and Tamar Nijsten",
year = "2017",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0169873",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Genome-wide association studies of multiple keratinocyte cancers

AU - Pardo, Luba M.

AU - Li, Wen Qing

AU - Hwang, Shih Jen

AU - Verkouteren, Joris A.C.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Kraft, Peter

AU - Turman, Constance

AU - Han, Jiali

AU - Cho, Eunyoung

AU - Murabito, Joanne M.

AU - Levy, Daniel

AU - Qureshi, Abrar A.

AU - Nijsten, Tamar

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 genomewide 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 (pvalue ≤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 (pvalue = 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.

AB - 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 genomewide 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 (pvalue ≤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 (pvalue = 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.

UR - http://www.scopus.com/inward/record.url?scp=85009420590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009420590&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0169873

DO - 10.1371/journal.pone.0169873

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0169873

ER -