Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors

65Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

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. Copyright © 2007 American Association for Cancer Research.

References Powered by Scopus

Haploview: Analysis and visualization of LD and haplotype maps

12731Citations
N/AReaders
Get full text

p53 mutations in human cancers

7873Citations
N/AReaders
Get full text

A new statistical method for haplotype reconstruction from population data

6672Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Biomarker development in the precision medicine era: Lung cancer as a case study

444Citations
N/AReaders
Get full text

A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms

305Citations
N/AReaders
Get full text

Lung cancer epigenetics and genetics

215Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Mechanic, L. E., Bowman, E. D., Welsh, J. A., Khan, M. A., Hagiwara, N., Enewold, L., … Harris, C. C. (2007). Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors. Cancer Epidemiology Biomarkers and Prevention, 16(2), 214–222. https://doi.org/10.1158/1055-9965.EPI-06-0790

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 13

62%

Researcher 5

24%

Professor / Associate Prof. 3

14%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 7

32%

Medicine and Dentistry 7

32%

Biochemistry, Genetics and Molecular Bi... 7

32%

Computer Science 1

5%

Save time finding and organizing research with Mendeley

Sign up for free