Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype

Abstract

A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.

Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

“…Several studies exhibit this deviation in the control (Jin et al, 1995;Makni et al, 2000) or patients group (Kawajiri et al, 1993;Tandle et al, 2001). This cannot be attributed to methodological problems.…”

A P53 Genetic Polymorphism As A Modulator of Hepatocellular Carcinoma Risk in Relation to Chronic Liver Disease, Familial Tendency, and Cigarette Smoking in Hepatitis B Carriers

“…[25][26][27] We therefore hypothesized that the risk of HCC in relation to the p53 polymorphism may depend on individuals' smoking status and genotypes of enzymes involved in the metabolic activation or detoxification of procarcinogens in tobacco smoke. No notable interaction was identified between cigarette smoking and the p53 genotypes.…”

“…31 Polymorphisms in the intron 3, exon 4 (codon 72), and intron 6 of the gene have been evaluated in case-control studies for risk of various cancers, and the results have been mixed. [25][26][27][28][29][30][31][32] No functional significance of these polymorphisms is currently known. The hypothesized relationship of the codon 72 p53 polymorphism to cancer susceptibility does not yet have a mechanistic basis.…”

“…[25][26][27][28][29] For Japanese, risk increased approximately twofold for smoking-related lung cancer among individuals carrying the Pro/Pro genotype compared with those with other genotypes of the codon 72 p53 polymorphism. 25 Among blacks and Mexicans in the United States, the OR of lung cancer associated with the Pro/Pro genotype was significantly elevated only among younger patients and light smokers.…”

“…The functional significance of the variant is unknown, but the Pro variant allele of this p53 polymorphism has been studied as a potential risk factor for cancer of the lung, breast, and large bowel, with inconsistent results. [25][26][27][28][29][30][31][32] This study was performed to examine whether the p53 codon 72 polymorphism was associated with susceptibil-ity to HCC using a case-control study nested in a large cohort study of men with chronic HBV infection. Also evaluated were any interactions of the p53 polymorphism with putative HCC risk factors in hepatocarcinogenesis.…”