The p53 codon 72 polymorphism and lung cancer risk

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• The p53 tumor suppressor gene is frequently mutated in human carcinomas.
• A common polymorphism in p53 at codon 72 (Arg/Pro) is linked to lung cancer susceptibility, but findings are inconsistent.
• This polymorphism may influence individual responses to environmental carcinogens like tobacco smoke.

Purpose of the Study:

• To investigate the association between the p53 codon 72 polymorphism and lung adenocarcinoma risk.
• To determine if smoking modifies the risk associated with the p53 Pro/Pro genotype.
• To assess the role of p53 germ-line variation in heritable susceptibility to smoke-induced lung cancer.

Main Methods:

• A large case-control study involving 482 lung cancer cases and 510 controls.
• Analysis of DNA from peripheral blood samples using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
• Statistical adjustment for relevant variables, including smoking pack-years.

Main Results:

• Pro/Pro homozygotes were more frequent in lung adenocarcinoma cases (16.4%) than controls (12.0%), P = 0.03.
• The Pro/Pro genotype prevalence increased with higher smoking pack-years.
• The combined Arg/Pro and Pro/Pro genotypes showed a 1.45-fold increased risk of adenocarcinoma (95% CI = 1.01-2.06, P = 0.04) compared to Arg/Arg, particularly with increased tobacco exposure.

Conclusions:

• The p53 codon 72 polymorphism (Arg/Pro) contributes to heritable susceptibility for smoke-induced lung adenocarcinoma.
• Smoking significantly modifies the risk associated with p53 genotypes, increasing susceptibility.
• p53 germ-line variations may modulate the impact of environmental carcinogens on lung adenocarcinoma development.