Abstract
BackgroundXeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive.Methodology/Principal FindingsIn this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR = 0.87, 95% CI = 0.76–1.00, P = 0.049, P = 0.723 for heterogeneity test, I2 = 0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student’s t test for a recessive model: P = 0.046). No publication bias was found by using the funnel plot and Egger’s test.ConclusionThis meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.
Highlights
Nucleotide excision repair (NER) is the most versatile, well studied DNA repair mechanism in humans, mainly responsible for repairing bulky DNA damage, such as DNA adducts caused by UV radiation, mutagenic chemicals, or chemotherapeutic drugs [1]
This meta-analysis suggests a lack of statistical evidence for the association between the four xeroderma pigmentosum complementation group F (XPF) SNPs and overall risk of cancers
XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies
Summary
Nucleotide excision repair (NER) is the most versatile, well studied DNA repair mechanism in humans, mainly responsible for repairing bulky DNA damage, such as DNA adducts caused by UV radiation, mutagenic chemicals, or chemotherapeutic drugs [1]. One of the NER genes, xeroderma pigmentosum complementation group F (XPF), called excision repair cross-complimentary group 4 (ERCC4), is located on chromosome 16p13.12, contains 11 exons and spans approximately 28.2 kb (Figure 1B) [5]. It is a key component involved in the 59 incision made during NER [2]. In addition to NER, this complex is suggested to play a role in removal of DNA interstrand cross-links (ICL) [10] and DNA double-strand breaks (DSB) as well [11]. Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive
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