Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway.
The genetic susceptibility hypothesis has been used to explain why only a minority of smokers develop lung cancer. Only few studies have studied the role of polymorphisms in phase-I and II metabolizing genes, among young lung cancer patients. We have pooled the individual data of three studies from Denmark and Norway, including 320 patients diagnosed with non-small cell lung cancer at age 59 or below, and 618 age and gender matched controls. A questionnaire was used to determine relevant demographic and lifestyle characteristics, and polymorphisms in following genotypes were determined GSTM1, GSTM3, GSTP1, GSTT1, GPX1, MPO, NQO1 and NAT2. Based on the literature, the alleles of the genotypes were categorised as high- or low-risk alleles. No individual effect of the genotypes was found on the risk of lung cancer. Given a smoking exposure, the presence of high-risk alleles (or phenotypes) was generally found to increase the risk of lung cancer, although the effect modification did not reach statistical significance. A pattern of stronger protective effect was observed in carriers of more than one allele associated with lower risk of lung cancer, and a higher risk of lung cancer in carriers of one or more alleles associated with higher risk of lung cancer, but the results did not reach statistical significance. The effect modification was generally strongest at lower levels of smoking.
Skuladottir
Halla
H
Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark. halla@cancer.dk
Autrup
Herman
H
Autrup
Judith
J
Tjoenneland
Anne
A
Overvad
Kim
K
Ryberg
David
D
Haugen
Aage
A
Olsen
Jørgen H
JH
D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D004785:Environmental Pollutants / Q000378:metabolism* / Q000506:poisoning*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D014166:Transferases / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism* / Q000506:poisoning*
D004785:Environmental Pollutants; D015262:Xenobiotics; D010544:Peroxidases; D014166:Transferases