Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years.
BACKGROUND
Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis.


METHODS
246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped.


RESULTS
Genetic associations or gene-smoking interactions was found for GPX1(Pro200Leu) and EPHX1(His113Tyr). Carriers of the Leu-allele of GPX1(Pro200Leu) showed a significant risk reduction of OR = 0.6 (95% CI: 0.4-0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1-0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of EPHX1(His113Tyr) for moderate smokers (OR = 0.2, 95% CI:0.1-0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07-0.60) for each protective allele.


CONCLUSIONS
Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of GPX1(Pro200Leu) and the C-Allele of EPHX1(His113Tyr) to play a protective role in early onset lung cancer susceptibility.
Rosenberger
Albert
A
Department of Genetic Epidemiology, Georg-August University of Göttingen, Medical School, Germany. arosenb@gwdg.de
Illig
Thomas
T
Korb
Katrin
K
Klopp
Norman
N
Zietemann
Vera
V
Wölke
Gabi
G
Meese
Eckart
E
Sybrecht
Gerhard
G
Kronenberg
Florian
F
Cebulla
Matthias
M
Degen
Maria
M
Drings
Peter
P
Gröschel
Andreas
A
Konietzko
Nikolaus
N
Kreymborg
Karsten Grosse
KG
Häussinger
Karl
K
Höffken
Gerd
G
Jilge
Bettina
B
Ko
You-Dschun
YD
Morr
Harald
H
Schmidt
Christine
C
Schmidt
E-Wilhelm
EW
Täuscher
Dagmar
D
Bickeböller
Heike
H
Wichmann
H-Erich
HE
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005858:Germany; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D000094765:Glutathione Peroxidase GPX1
D005819:Genetic Markers; D005979:Glutathione Peroxidase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human