Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study.
OBJECTIVE
Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk.


METHODS
We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).


RESULTS
Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66-3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend=0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear associations were observed for GSTT1 genotypes.


CONCLUSIONS
Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer.
Lam
Tram Kim
TK
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Ruczinski
Ingo
I
Helzlsouer
Kathy
K
Shugart
Yin Yao
YY
Li
Kelly E
KE
Clipp
Sandra
S
Strickland
Paul T
PT
Alberg
Anthony J
AJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D004522:Educational Status; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1