In Xuan Wei County, Yunnan Province, lung cancer mortality is among China's highest and, especially in females, is more closely associated with indoor burning of "smoky" coal, as opposed to wood or "smokeless" coal, than with tobacco smoking. Indoor air samples were collected during the burning of all three fuels. In contrast to wood and smokeless coal emissions, smoky coal emission has high concentrations of submicron particles containing mutagenic organics, especially in aromatic and polar fractions. These studies suggested an etiologic link between domestic smoky coal burning and lung cancer in Xuan Wei.

The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR 5 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR 5 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR 5 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs. ' 2005 Wiley-Liss, Inc.Key words: lung cancer; DNA repair; single nucleotide polymorphism; nucleotide excision repair; polycyclic aromatic hydrocarbon Lung cancer is the leading cause of death from cancer worldwide, with an estimated mortality in 2000 of 31.4 per 100,000 for men and 9.5 per 100,000 for women. 1 Overall, lung cancer incidence and mortality rates are higher for males than females, due largely to the higher prevalence of tobacco smoking among men. Compared to worldwide patterns and those in China, lung cancer has distinctive characteristics in rural Xuan Wei County, Yunnan Province, China. Lung cancer mortality in Xuan Wei has been reported to be 8 times the Chinese national average for women and 4 times that for men. 2 Although very few women smoke, the lung cancer mortality rates in Xuan Wei County were similar between men and women (27.7 and 25.3 per 100,000 for males and females, respectively). 2 This pattern has been attributed to burning smoky coal indoors for heating and cooking without adequate ventilation with high exposure time, particularly among women, accounting for >90% of lung cancer cases for both men and women. 2,3 When smoky coal is burned, the indoor air concentration of particulate matter and extractable organic matter may be as high as 24.4 and 17.6 mg/m 3 , 2 respectively, and the corresponding benzo[a]pyrene concentration, an indicator of carcinogenic PAHs, can reach as high as 19.3 lg/m 3 , 4 which is comparable to exposure levels experien...

The lung cancer mortality rate in Xuan Wei (XW) county, China, is 5-fold the national average of China; the rate for women is the highest in China. Xuan Wei residents have been exposed to unvented coal or wood smoke during cooking or heating in homes. This study investigated indoor air exposure and dosimetry of polycyclic aromatic hydrocarbons (PAHs) in XW residents using smoky coal. Indoor air particles collected during cooking in four XW homes using smoky coal were analyzed for PAHs by GC/MS. Urine samples from 16 XW non-smoking women and six XW smoking men, eight Kunming non-smoking controls and four non-smoking Chinese American controls were analyzed for PAHs and hydroxy-PAHs by GC/MS. The results showed that XW residents were exposed to PAHs at occupational levels. The potent carcinogen, dibenzo[a,l] pyrene (4.9 +/- 1.3 micrograms/m3) was found in the indoor air of the XW homes. The levels of urinary hydroxy-PAH were higher than those of the parent compounds in most subjects, indicating that most PAHs were metabolized. In urine, the mean levels of 9-hydroxy BaP (BaP) and BaP are 1.5 +/- 0.5 mumol/mol creatinine and 0.5 +/- 0.3 microns/mol for XW men, 1.9 +/- 0.9 microns/mol and 0.5 +/- 0.3 microns/mol for XW women. In general, the levels of PAH metabolites in urine were higher in the XW residents than in Kunming and Chinese American controls; however only the concentrations of 9-hydroxy BaP in XW women showed statistically significant difference from the Kunming controls (P < 0.05 by ranking test). The mean levels of 3 methylated-PAHs analyzed were 4.8-fold higher than that of the parent PAHs in XW subjects. This is consistent with previous findings that alkylated PAHs are the major mutagens in the XW indoor air and may be etiologically important in XW lung cancer.