Abstract
Numerous studies have explored the influence of XPD Lys751Gln and/or Asp312Asn polymorphisms on skin cancer susceptibility. However, the results remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all available published studies and performed a meta-analysis. Electronic literature searches of the PubMed, CBM and CNKI databases were performed up to March 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Seventeen case-control studies were included with a total sample size of 6, 113 cases and 11, 074 controls for the XPD Lys751Gln polymorphism, and 10 studies (3, 840cases and 7, 637 controls) for the XPD Asp312Asn polymorphism were pooled for analysis. Overall, no significant associations were found between the XPD Lys751Gln polymorphism and skin cancer risk in any genetic model. On stratified analysis by tumor type, XPD Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: OR=1.15, 95%CI=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036). For the XPD Asp312Asn polymorphism, no significant association with skin cancer risk was observed in overall or subgroup analyses. The present meta-analysis suggests that the XPD Lys751Gln polymorphism may contribute to the risk of cutaneous melanoma from currently available evidence. Further investigations are needed to obtain more insight into possible roles of these two polymorphisms in skin carcinogenesis.
Highlights
Skin cancer, one of the most common neoplasms, has been an important public health problem in most Caucasian populations with the increasing incidence during the last few years (Leiter and Garbe, 2008)
On stratified analysis by tumor type, Xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: Odds ratios (ORs)=1.15, 95%confidence intervals (CIs)=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036)
Studies were required to comply with the following inclusion criteria: (1) case-control studies; (2) the studies should evaluate the association of XPD Lys751Gln and/or Asp312Asn polymorphisms with risk of skin cancer; (3) sufficient information to calculate odds ratios (ORs) with 95% confidence intervals (CIs); (4) For multiple publications reporting on overlapping data, only the most recent, largest or complete study was selected; and (5) the distributions of genotypes among controls conformed to the HardyWeinberg equilibrium (HWE) ( Salanti et al, 2005)
Summary
One of the most common neoplasms, has been an important public health problem in most Caucasian populations with the increasing incidence during the last few years (Leiter and Garbe, 2008). Numerous studies have explored the influence of XPD Lys751Gln and/or Asp312Asn polymorphisms on skin cancer susceptibility. To derive a more precise estimation, we conducted a comprehensive search to identify all available published studies and performed a meta-analysis. No significant associations were found between the XPD Lys751Gln polymorphism and skin cancer risk in any genetic model. On stratified analysis by tumor type, XPD Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: OR=1.15, 95%CI=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036). For the XPD Asp312Asn polymorphism, no significant association with skin cancer risk was observed in overall or subgroup analyses. Conclusions: The present meta-analysis suggests that the XPD Lys751Gln polymorphism may contribute to the risk of cutaneous melanoma from currently available evidence. Further investigations are needed to obtain more insight into possible roles of these two polymorphisms in skin carcinogenesis
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