Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors
Open Access
- 1 February 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 16 (2), 214-222
- https://doi.org/10.1158/1055-9965.epi-06-0790
Abstract
Lung cancer is primarily caused by tobacco smoking, but susceptibility is likely modified by common genetic variation. In response to many forms of cellular stress, including DNA damage, the p53 protein functions to induce cell cycle arrest, DNA repair, senescence, or apoptosis. We hypothesized that common TP53 haplotypes modulate pathways of lung carcinogenesis and lung cancer susceptibility or prognosis. To investigate our hypothesis, 14 polymorphisms in TP53, including haplotype tagging and coding single nucleotide polymorphisms, were genotyped in two studies from the greater Baltimore, Maryland area. One study is a case-control study and the second is a case-only study for which TP53 mutational spectra data are available. African Americans with Pro-T-A-G-G haplotypes of the combined TP53 polymorphisms TP53_01 (rs1042522), TP53_65 (rs9895829), TP53_66 (rs2909430), TP53_16 (rs1625895), and TP53_11 (rs12951053) had both an increased risk for lung cancer (odds ratio, 2.32; 95% confidence interval, 1.18-4.57) and a worsened lung cancer prognosis (hazards ratio, 2.38; 95% confidence interval, 1.38-4.10) compared with those with Arg-T-A-G-T haplotypes. No associations of TP53 polymorphisms with lung cancer were observed in Caucasians. In the case-only study, several polymorphisms in TP53 and TP53 haplotypes, overlapping regions of TP53 associated with risk and prognosis in African Americans, were associated with increased odds of somatic TP53 mutation in lung tumors in Caucasians. In conclusion, common genetic variation in TP53 could modulate lung cancer pathways, as suggested by the association with lung cancer in African Americans and somatic TP53 mutation frequency in lung tumors. (Cancer Epidemiol Biomarkers Prev 2007;16(2):214–22)This publication has 49 references indexed in Scilit:
- Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the WorldJournal of Clinical Oncology, 2006
- Molecular Epidemiology of Non-Small Cell Lung CancerSeminars in Respiratory and Critical Care Medicine, 2005
- Risk assessment of p53 genotypes and haplotypes in tobacco‐associated leukoplakia and oral cancer patients from eastern indiaInternational Journal of Cancer, 2005
- p53 polymorphisms in Russia and Belarus: correlation of the 2-1-1 haplotype frequency with longitudeMolecular Genetics and Genomics, 2005
- Evaluating associations of haplotypes with traitsGenetic Epidemiology, 2004
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- Detailed computational study of p53 and p16: using evolutionary sequence analysis and disease-associated mutations to predict the functional consequences of allelic variantsOncogene, 2003
- Haplotype and Linkage Disequilibrium Architecture for Human Cancer-Associated GenesGenome Research, 2002
- Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancersOncogene, 2002
- Mutations in the p53 gene occur in diverse human tumour typesNature, 1989