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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

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XPC polymorphisms play a role in tissue-specific carcinogenesis: a meta-analysis.

Guilherme Francisco¹, Paulo Rossi Menezes, José Eluf-Neto

¹Laboratório de Oncologia Experimental LIM-24, Departamento de Radiologia, Faculdade de Medicina da Universidade de São Paulo, Avenida Dr Arnaldo 455, São Paulo, SP, Brazil.

European Journal of Human Genetics : EJHG

|February 21, 2008

Summary

Genetic variations in the Xeroderma pigmentosum complement group C (XPC) gene are linked to DNA repair. This meta-analysis found XPC polymorphisms may increase susceptibility to lung, bladder, and other cancers.

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Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker

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Area of Science:

Genetics
Molecular Biology
Cancer Research

Background:

The Xeroderma pigmentosum complement group C (XPC) protein is crucial for DNA damage recognition in global genomic repair.
Previous studies on XPC gene polymorphisms and cancer risk have yielded conflicting results.
Clarifying the role of XPC variants in cancer susceptibility is important for understanding disease etiology.

Purpose of the Study:

To conduct a meta-analysis to clarify the impact of XPC gene polymorphisms on cancer risk.
To investigate the association between specific XPC polymorphisms (Lys939Gln and Ala499Val) and overall cancer risk.
To examine the association of these polymorphisms with the risk of specific cancer types, including lung, breast, and bladder cancer.

Main Methods:

A meta-analysis was performed, pooling data from 33 published case-control studies.
The study analyzed two common XPC polymorphisms: Lys939Gln and Ala499Val.
Statistical analyses included calculation of overall odds ratios (OR) and confidence intervals (CI) using various genetic models.

Main Results:

The Lys939Gln polymorphism showed a significant association with increased lung cancer risk under a recessive model (OR 1.30).
The Ala499Val polymorphism was associated with a significant overall increase in cancer risk (OR 1.15) and specifically with bladder cancer risk under both simple and recessive models (ORs 1.30 and 1.32, respectively).
No significant association was found for the Lys939Gln polymorphism with overall cancer risk or breast cancer risk.

Conclusions:

XPC gene polymorphisms, particularly Ala499Val, may act as low-penetrance susceptibility variants for several common cancers, including lung, bladder, head and neck, and breast cancer.
These findings suggest XPC is a potential candidate gene for further large-scale epidemiological studies.
Improved understanding of XPC's role in DNA repair and cancer susceptibility could aid in the management of prevalent cancers.