Influence of TGFB1+869T>C functional polymorphism in non-small cell lung cancer (NSCLC) risk.
OBJECTIVE
Lung cancer is the third most common type of cancer in Europe and is the first cause of death by cancer worldwide. Non-small cell lung cancer accounts for 75-85% of all histological types of LC. The transforming growth factor beta 1 is a multifunctional regulatory polypeptide that controls many aspects of cellular function (cellular proliferation, differentiation, migration, apoptosis, immune surveillance). TGFB1+869T>C is a functional polymorphism described in TGFB1 gene and this transition has been associated with higher circulating levels of TGFß1 that may modulate cellular microenvironment and consequently LC development and prognosis.


METHODS
We studied TGFB + 869T > C functional polymorphism by allelic discrimination using 7300 real-time polymerase chain reaction system in 305 patients with NSCLC and 380 healthy individuals.


RESULTS
We found an increased risk for C carriers to develop NSCLC, both epidermoid NSCLC and non-epidermoid NSCLC (odds ratio (OR) = 2.03, P < 0.0001, OR = 2.37, P < 0.001 and OR = 1.83, P = 0.001, respectively). TGFB1+869T>C functional polymorphism may influence NSCLC susceptibility with impact in cellular microenvironment.


CONCLUSIONS
Our results suggest that individual differences influence the susceptibility to LC and tumoral behavior. This genetic profiling may help define higher risk groups for an individualized chemoprevention strategy and therapy.
Teixeira
Ana L
AL
Molecular Oncology GRP-CI, Portuguese Institute of Oncology, Porto Centre, Edifício Laboratórios, 4º piso, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
Araújo
António
A
Coelho
Ana
A
Ribeiro
Ricardo
R
Gomes
Mónica
M
Pereira
Carina
C
Medeiros
Rui
R
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
Dis Markers. 2005;21(3):157-65
16276011
J Clin Oncol. 2005 Mar 20;23(9):2078-93
15774796
Cancer Genet Cytogenet. 2006 Aug;169(1):39-44
16875935
Nat Rev Cancer. 2003 Nov;3(11):807-21
14557817
Expert Opin Biol Ther. 2003 Apr;3(2):251-61
12662140
J Cancer Res Clin Oncol. 2008 Mar;134(3):345-51
17680270
Cancer Res. 1999 Oct 1;59(19):4834-42
10519393
Cancer Biol Ther. 2004 Mar;3(3):276-83
15034302
Lung Cancer. 2006 Apr;52(1):1-7
16499994
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1303-5
17548703
Circulation. 2000 Jun 20;101(24):2783-7
10859282
Clin Cancer Res. 2008 Aug 1;14(15):4961-70
18676771
Cancer Epidemiol Biomarkers Prev. 2004 May;13(5):759-64
15159307
Cancer Res. 1996 Dec 15;56(24):5583-5
8971158
Curr Cancer Drug Targets. 2006 Nov;6(7):565-78
17100564
Cancer Res. 1996 Jun 15;56(12):2718-20
8665501
Microsc Res Tech. 2001 Feb 15;52(4):363-73
11170295
Cell Biochem Funct. 2008 Apr;26(3):283-90
17654453
Cancer. 1999 Nov 1;86(9):1712-9
10547543
Carcinogenesis. 2007 Sep;28(9):1965-70
17615257
Clin Chim Acta. 2007 May 1;380(1-2):165-9
17368597
Anticancer Res. 1999 Jan-Feb;19(1A):301-6
10226558
Carcinogenesis. 2004 Feb;25(2):237-40
14604900
Curr Opin Pulm Med. 2004 Jul;10(4):279-83
15220752
Pharmacogenomics J. 2009 Oct;9(5):341-6
19488063
N Engl J Med. 2004 Jan 22;350(4):379-92
14736930
Hum Mol Genet. 1999 Jan;8(1):93-7
9887336
Int J Cancer. 2004 Oct 20;112(1):94-9
15305380
Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):412-5
15006917