Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk

Jiali Han, Graham A. Colditz, Leona D. Samson, David J. Hunter

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 1808ST (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.

Original languageEnglish (US)
Pages (from-to)3009-3013
Number of pages5
JournalCancer Research
Volume64
Issue number9
DOIs
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Double-Stranded DNA Breaks
Skin Neoplasms
Basal Cell Carcinoma
Alleles
Haplotypes
Genes
Squamous Cell Carcinoma
Melanoma
DNA Replication
DNA Damage
Single Nucleotide Polymorphism
Case-Control Studies
Nurses
Genotype
DNA
Health

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk. / Han, Jiali; Colditz, Graham A.; Samson, Leona D.; Hunter, David J.

In: Cancer Research, Vol. 64, No. 9, 01.05.2004, p. 3009-3013.

Research output: Contribution to journalArticle

Han, Jiali ; Colditz, Graham A. ; Samson, Leona D. ; Hunter, David J. / Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk. In: Cancer Research. 2004 ; Vol. 64, No. 9. pp. 3009-3013.
@article{8d7ed8663b8a485ab5fe9801ceb59411,
title = "Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk",
abstract = "UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 1808ST (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.",
author = "Jiali Han and Colditz, {Graham A.} and Samson, {Leona D.} and Hunter, {David J.}",
year = "2004",
month = "5",
day = "1",
doi = "10.1158/0008-5472.CAN-04-0246",
language = "English (US)",
volume = "64",
pages = "3009--3013",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk

AU - Han, Jiali

AU - Colditz, Graham A.

AU - Samson, Leona D.

AU - Hunter, David J.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 1808ST (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.

AB - UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 1808ST (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.

UR - http://www.scopus.com/inward/record.url?scp=2342512130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342512130&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-0246

DO - 10.1158/0008-5472.CAN-04-0246

M3 - Article

C2 - 15126335

AN - SCOPUS:2342512130

VL - 64

SP - 3009

EP - 3013

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 9

ER -