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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Elevated risk of squamous-cell carcinoma of the lung in heavy smokers carrying the variant alleles of the TP53
Odilia Popanda1, Lutz Edler, Peter Waas
1Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. o.popanda@dkfz-heidelberg.de
Abstract:
Alterations in cell cycle regulation and apoptosis leading to malignant transformation could be caused by common genetic variants in tumor suppressor genes. The effects of the TP53 polymorphism Arg72Pro on lung cancer risk have been investigated in numerous studies with, however, conflicting results. In many studies, important risk modifiers such as smoking or tumor histology were not taken into account. We therefore investigated the combined effects of polymorphisms in TP53 (Arg72Pro) and p21/CDKN1A (Ser31Arg) and smoking on lung cancer risk. Our case-control study consisted of 405 patients with lung cancer, mainly squamous-cell carcinoma (185) and adenocarcinoma (177) and 404 unmatched tumor-free hospital controls. Multivariate regression analysis showed a moderate but statistically significant risk of lung cancer overall and especially of squamous-cell carcinoma (OR, 1.65; CI, 1.10-2.47) for TP53 72Pro allele carriers. The risk was markedly increased in heavy smokers (>20 pack-years) with squamous-cell carcinoma (OR, 2.80 in patients homozygous for 72Pro; CI, 1.19-6.58), but not in light smokers (
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