787d4ee2-5392-467a-b29f-4c0ede068ecb
title
Polymorphisms in DNA double-strand break repair genes and skin cancer risk.
7d887035-7a41-4f37-9331-3a20dfd8a3b2
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   18085T (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.