GSTM1 and CYP1A1 polymorphisms, tobacco, air pollution, and lung cancer: a study in rural Thailand.
OBJECTIVE
The Lampang Province is situated in the northern region of Thailand. Incidence rates of lung cancer are high for Asian standards, particularly in women. This study was conducted to quantify the risk of lung cancer associated with exposures prevalent in the area and to investigate possible interactions with genetic susceptibility. The presence of several large open-cast coal mines from 1955 close to electricity-generating plants was a particular focus of concern.


METHODS
Two-hundred and eleven cases of primary lung cancers diagnosed in 1993 to 1995 and residents in the province were recruited at the Lampang Provincial Hospital (main referral center for treatment of the disease). Two sets of controls, frequency-matched to the cases by sex and age, were recruited (a) from the resident population (202 interviewed) and (b) from patients admitted to the hospital for diseases predominantly unrelated to tobacco smoking (211 interviewed). Sociodemographic information, complete residential history, and characteristics of the household (place of cooking, cooking fuel, and heating fuels), occupational history, and history of tobacco smoking were obtained by interview. Cases and controls ( approximately 50% of the population-based series) provided a blood sample. A point source air pollution exposure index was calculated for each village/township reported in residential histories based on the linear distance from the Mae Moh Center (the area of the electricity-generating plants), the year-specific gaseous (SO(2) and NO(2)) or total suspended particulate emissions from the Mae Moh Power Plant, and the percentage of wind from the center. Odds ratios (OR) for the disease associated with categorical variables were estimated within unconditional logistic regression. Extraction of genomic DNA and genotyping of variants in CYP1A1 and GSTM1 were conducted to assess the extent of modification of risk by these genes that are involved in the metabolism of polycyclic aromatic hydrocarbons, a common component of the exposures.


RESULTS
Overall, there was no evidence of relevant differences in the socioeconomic level of the three groups. The two control sets were similar with respect to lifelong tobacco habit and were subsequently pooled in analyses. Never-smokers were 7% of men and 33% of women. Smoking of local traditional products unfiltered and high in tar content is a common habit in the rural female population. ORs associated with smoking increased with duration of the habit and average daily amount, being 4.9 [95% confidence interval (95% CI), 2.5-9.7] for smokers of > or =7 cigarettes/d and 3.3 (95% CI, 1.7-6.2) for duration of 41 years or longer compared with nonsmokers. Smoking of local products was associated with an independent OR of 3.1 (95% CI, 1.7-5.6) adjusted for lifelong cumulative amount of tobacco smoked. Although most smokers had the habit for at least 16 years, the daily consumption was low compared with Western standards. Other potential sources of exposure to lung carcinogens (emission from the power-generating plants and domestic burning of coal and wood for cooking and heating) were not associated with increased risk of lung cancer. None of the three polymorphisms examined increased the risk of lung cancer or modified the risk associated with tobacco smoking.


CONCLUSIONS
In this rural population, 96% of male and 64% of female lung cancer incidence were explained by tobacco smoking. None of the potential sources of air pollution deriving from the combustion of coal and wood, or polymorphisms in the CYP1A1 gene or deletion of the GSTM1 had an effect on the risk of lung cancer, either together or separately.
Pisani
Paola
P
Descriptive Epidemiology Group, IARC, Lyons, France. pisani@iarc.fr
Srivatanakul
Petcharin
P
Randerson-Moor
Juliette
J
Vipasrinimit
Sutee
S
Lalitwongsa
Somkiat
S
Unpunyo
Piyapong
P
Bashir
Saghir
S
Bishop
D Timothy
DT
D000367:Age Factors; D000368:Aged; D016902:Air Pollution, Indoor / Q000009:adverse effects*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012424:Rural Population; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013785:Thailand / Q000453:epidemiology; D014026:Nicotiana
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase