Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a...

Area of Science:

• Genetics and Cancer Epidemiology
• Molecular Biology and Disease Mechanisms

Background:

• Numerous studies have explored the link between Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms (Asp312Asn and Lys751Gln) and bladder cancer risk.
• Existing research presents conflicting conclusions, necessitating a comprehensive meta-analysis to clarify these associations.

Purpose of the Study:

• To conduct a meta-analysis evaluating the association between XPD Asp312Asn (rs1799793) and Lys751Gln (rs13181) polymorphisms and bladder cancer risk.
• To investigate the impact of these polymorphisms on XPD gene expression across different ethnicities.

Main Methods:

• Systematic literature search of PubMed, Embase, and CBM databases.
• Meta-analysis of 11 studies (3,797 cases, 5,094 controls) for Asp312Asn and 21 studies (6,360 cases, 7,894 controls) for Lys751Gln.
• Calculation of odds ratios (ORs) and 95% confidence intervals (CIs); gene expression analysis based on imputed genotypes.

Main Results:

• The Asp312Asn polymorphism was significantly associated with increased bladder cancer risk across multiple genetic models (ORs ranging from 1.23 to 1.51).
• The Lys751Gln polymorphism showed an association with increased bladder cancer risk specifically under the recessive model (OR = 1.14).
• Stratification revealed increased risk for Asians and in hospital-based studies for Asp312Asn, and for Caucasians for Lys751Gln. Both polymorphisms influenced XPD mRNA levels in specific ethnic groups.

Conclusions:

• Polymorphisms in the XPD gene, particularly Asp312Asn and Lys751Gln, are implicated in bladder cancer susceptibility.
• The findings suggest a potential role for XPD variants in the development of bladder cancer.
• Further validation through large prospective studies is recommended to confirm these associations.