[Survival in Lung Cancer among Female Never-smokers in Rural Xuanwei 
and Fuyuan Counties in Eastern Yunnan Province, China].

BACKGROUND: Lung cancer rates among women in rural Xuanwei and Fuyuan counties in eastern Yunnan province, China, are among the highest in the world, even though almost all women are non-smokers, and they tend to develop lung cancer at a younger age than other locations by roughly 5 yr-10 yr. This study investigated the survival of lung cancer patients among female never-smokers. METHODS: The female never-smokers, who had lived for many years in Xuanwei and Fuyuan counties, with lung cancer newly-diagnosed between July 2006 to March 2010, were followed up through the end of 2016. Age-standardized relative survival for all cases was calculated using local life table. The Kaplan-Meier method and Log-rank test were used to analyze the relationship between the variables and the prognosis in univariate analysis. Cox regression analysis was employed in the multivariate analysis. RESULTS: Among 1,250 total subjects, 1,075 died and the remaining 175 were censored during the follow-up, with a median follow-up period of 69 months (95%CI: 61.9-76.0). Overall, the mean age was (54.8 ±10.9) yr, with variable clinical stages: 3.5% of cases were stage I, 8.7% stage II, 20.7% stage III, 29.7% stage IV, and 37.4% stage unknown. The 645 patients(51.6%) with cyto-histological diagnosis contains 303 with Squamous cell carcinoma, and 231 with adenocarcinoma, 24 with small cell, 43 with other specified type and 39 with unknown histological type. Only 215 (17.2%) patients received surgery, 487 (39.0%) were treated without surgery, and 548 (43.8%) did not receive any specific anticancer therapy. The 5-year observed survival rate and age-standardized relative survival were 8.9% (95%CI: 7.0-10.6), and 10.1% (95%CI: 3.7-20.5) respectively, with a median survival of 13.2 months. The 5-year survival rates were 41.1% for stage I, 22.4% for stage II, 5.3% for stage III, 1.3% for stage IV, 11.2% for missing stage, 17.9% for adenocarcinoma, and 5.6% for squamous cell carcinoma respectively. Surgery significantly improved 5-year survival rate compared with non-surgery (34.8% vs 3.2%, P<0.001). The patients with non-treatment, aged 65 years and older, living in rural areas and farmer with low socioeconomic status had poorer survival, whereas the patients treated in provincial hospitals and chest X-ray screening had better survival. Cox multivariate analysis further showed that stage of tumor-node-metastasis (TNM), treatment status, hospital-level, and X-ray screening were factors correlated with survival. CONCLUSIONS: Patients with lung cancer among female never-smokers in Xuanwei and Fuyuan experience poorer survival, because they are less likely to be diagnosed at early stage, as well as less likely to receive surgery and comprehensive treatment. Furthermore low socioeconomic status and poor health security are also responsible for the low survival.

[Molecular epidemiology study in Xuanwei: the relationship among 
coal type, genotype and lung cancer risk].

BACKGROUND: It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County. METHODS: On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking history, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the association between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Software. RESULTS: Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3). There was marked heterogeneity in risk estimates for specific subtypes of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. The GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G) genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9 (1.1-3.3), respectively. Compared to subjects who with GSTM1-positive and used less than 130 tons of smoky coal during their lifetime, higher risks were closely associated with GSTM1-null and heavier users (≥130 tons), with the OR was 4.9 (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively. However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2), respectively. CONCLUSIONS: Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. The GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly associated with higher risk of lung cancer, especially among heavily exposed women.

Household air pollution and lung cancer in China: a review of studies in Xuanwei.

Over half of the world's population is exposed to household air pollution from the burning of solid fuels at home. Household air pollution from solid fuel use is a leading risk factor for global disease and remains a major public health problem, especially in low- and mid-income countries. This is a particularly serious problem in China, where many people in rural areas still use coal for household heating and cooking. This review focuses on several decades of research carried out in Xuanwei County, Yunnan Province, where household coal use is a major source of household air pollution and where studies have linked household air pollution exposure to high rates of lung cancer. We conducted a series of case-control and cohort studies in Xuanwei to characterize the lung cancer risk in this population and the factors associated with it. We found lung cancer risk to vary substantially between different coal types, with a higher risk associated with smoky (i.e., bituminous) coal use compared to smokeless (i.e., anthracite) coal use. The installation of a chimney in homes resulted in a substantial reduction in lung cancer incidence and mortality. Overall, our research underscores the need among existing coal users to improve ventilation, use the least toxic fuel, and eventually move toward the use of cleaner fuels, such as gas and electricity.

The potential role of lung microbiota in lung cancer attributed to household coal burning exposures.

Bacteria influence site-specific disease etiology and the host's ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH-rich household air pollution from burning coal. This study seeks to explore the role of lung microbiota in lung cancer among never smoking Xuanwei women and how coal burning may influence these associations. DNA from sputum and buccal samples of never smoking lung cancer cases (n = 8, in duplicate) and controls (n = 8, in duplicate) in two Xuanwei villages was extracted using a multi-step enzymatic and physical lysis, followed by a standardized clean-up. V1-V2 regions of 16S rRNA genes were PCR-amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. Bacterial diversity among cases and controls was similar in buccal samples (P = 0.46), but significantly different in sputum samples (P = 0.038). In sputum, Granulicatella (6.1 vs. 2.0%; P = 0.0016), Abiotrophia (1.5 vs. 0.085%; P = 0.0036), and Streptococcus (40.1 vs. 19.8%; P = 0.0142) were enriched in cases compared with controls. Sputum samples had on average 488.25 species-level OTUs in the flora of cases who used smoky coal (PAH-rich) compared with 352.5 OTUs among cases who used smokeless coal (PAH-poor; P = 0.047). These differences were explained by the Bacilli species (Streptococcus infantis and Streptococcus anginosus). Our small study suggests that never smoking lung cancer cases have differing sputum microbiota than controls. Further, bacteria found in sputum may be influenced by environmental exposures associated with the type of coal burned in the home.

Smoky coal, tobacco smoking, and lung cancer risk in Xuanwei, China.

OBJECTIVES: Lung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used. MATERIALS AND METHODS: We conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression. RESULTS: Use of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0-3 tons: OR: 1.09; 95% CI: 1.03-1.17; >3 tons: OR: 0.99; 95% CI: 0.95-1.03). Among more hazardous coal users, attenuation occurred at even low levels of usage (>0-3 tons: OR: 1.02; 95% CI: 0.91-1.14; >3 tons: OR: 0.94; 95% CI: 0.97-1.03). CONCLUSION: We found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as China's population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere.

History of lung disease and risk of lung cancer in a population with high household fuel combustion exposures in rural China.

History of chronic lung diseases and household coal use for heating and cooking are established risk factors of lung cancer; however, few studies have been able to explore these risk factors simultaneously. Xuanwei, China, has some of the highest rates of lung cancer in China and most residents experience substantial in-home coal smoke exposures. Using a population-based case-control study of 498 lung cancer cases and 498 age-matched controls, we evaluated the risk of lung cancer in relation to coal smoke exposure and history of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), chronic bronchitis, and emphysema. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression adjusting for potential confounders. We observed an increased risk of lung cancer with history of any chronic lung disease among males (OR = 14.2; 95%CI = 4.3-46.9), females (OR = 2.6; 95%CI = 1.1-6.3), smokers (OR = 12.7; 95%CI = 3.5-45.8), and nonsmokers (OR = 2.6; 95%CI = 1.1-6.4). Specifically, TB (OR = 83.7; 95%CI = 11.0-634.7), COPD (OR = 3.2; 95%CI = 1.7-6.0), and emphysema and chronic bronchitis (OR = 3.3; 95%CI = 1.7-6.4) were associated with increased risks. These findings suggest that history of chronic lung diseases may also increase risk of lung cancer in populations with indoor coal smoke exposures.

Coal mining is associated with lung cancer risk in Xuanwei, China.

BACKGROUND: Xuanwei, China, experiences some of the highest rates of lung cancer in China. While lung cancer risk has been linked to the household use of bituminous coal, no study has comprehensively evaluated the risk of lung cancer associated with the mining of this coal in Xuanwei. In Xuanwei, coal is typically extracted from underground mines, without ventilation, and transported to the surface using carts powered by manpower or electricity. METHODS: We evaluated the risk of lung cancer and working as a coal miner, in the absence of diesel exhaust exposure, in a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls with information on occupational histories. Odds ratios (ORs) and 95% confidence intervals (CIs) for working as a coal miner and years of working as a coal miner were calculated by conditional logistic regression, adjusting for potential confounders, such as smoking and household coal use. RESULTS: We observed an increased risk of lung cancer among coal miners (OR = 2.7; 95%CI = 1.3-5.6) compared to noncoal miners. Further, a dose-response relationship was observed for the risk of lung cancer and the number of years working as a coal miner (P(trend) = 0.02), with those working as miners for more than 10 years experiencing an almost fourfold increased risk (OR = 3.8; 95%CI = 1.4-10.3) compared to noncoal miners. CONCLUSIONS: These findings suggest that coal mining in Xuanwei may be a risk factor for lung cancer.

PTEN identified as important risk factor of chronic obstructive pulmonary disease.

Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P=0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (OR(TT)=0.12, 95% CI=0.03-0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures.

Well water arsenic exposure, arsenic induced skin-lesions and self-reported morbidity in Inner Mongolia.

Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 microg/L-10 microg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease.

Increased mortality associated with well-water arsenic exposure in Inner Mongolia, China.

We conducted a retrospective mortality study in an Inner Mongolian village exposed to well water contaminated by arsenic since the 1980s. Deaths occurring between January 1, 1997 and December 1, 2004 were classified according to underlying cause and water samples from household wells were tested for total arsenic. Heart disease mortality was associated with arsenic exposure, and the association strengthened with time exposed to the water source. Cancer mortality and all-cause mortality were associated with well-water arsenic exposure among those exposed 10-20 years. This is the first study to document increased arsenic-associated mortality in the Bayingnormen region of Inner Mongolia.

Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility.

Telomeres are responsible for the protection of the chromosome ends and shortened telomere length has been associated with risk of multiple cancers. Genetic variation in telomere-related genes may alter cancer risk associated with telomere length. Using lung cancer cases (n=120) and population-based controls (n=110) from Xuanwei, China, we analyzed telomere length separately and in conjunction with single nucleotide polymorphisms in the telomere maintenance genes POT1, TERT, and TERF2, which we have previously reported were associated with risk of lung cancer in this study. POT1 rs10244817, TERT rs2075786, and TERF2 rs251796 were significantly associated with lung cancer (p(trend)< or =0.05). The shortest tertile of telomere length was not significantly associated with risk of lung cancer (OR=1.58; 95% CI=0.79-3.18) when compared to the longest tertile of telomere length. When stratified by genotype, there was a suggestion of a dose-response relationship between tertiles of telomere length and risk of lung cancer among the POT1 rs10244817 common variant carriers (OR (95% CI)=1.33 (0.47-3.75), 3.30 (1.14-9.56), respectively) but not among variant genotype carriers (p(interaction)=0.05). Our findings provide evidence that telomere length and genetic variation in telomere maintenance genes may be associated with risk of lung cancer susceptibility and warrant replication in larger studies.

Coal use, stove improvement, and adult pneumonia mortality in Xuanwei, China: a retrospective cohort study.

BACKGROUND: In Xuanwei County, China, unvented indoor coal burning is strongly associated with increased risk of lung cancer and chronic obstructive pulmonary disease. However, the impact of coal burning and stove improvement on risk of pneumonia is not clear. METHODS: We conducted a retrospective cohort study among all farmers born 1917 through 1951 and living in Xuanwei as of 1 January 1976. The analysis included a total of 42,422 cohort members. Follow-up identified all deaths in the cohort from 1976 through 1996. Ages at entry into and at exit from follow-up ranged from 24 to 59 years and from 25 to 80 years, respectively. The record search detected 225 deaths from pneumonia, and 32,332 (76%) were alive as of 31 December 1996. We constructed multivariable Cox models (time variable = age) to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Use of coal, especially smokeless coal, was positively associated with pneumonia mortality. Annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality. Stove improvement was associated with a 50% reduction in pneumonia deaths (smoky coal users: HR, 0.521; 95% CI, 0.340-0.798; smokeless coal users: HR, 0.449; 95% CI, 0.215-0.937). CONCLUSIONS: Our analysis is the first to suggest that indoor air pollution from unvented coal burning is an important risk factor for pneumonia death in adults and that improving ventilation by installing a chimney is an effective measure to decrease it.

Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.

The high incidence of lung cancer in Xuanwei County, China has been attributed to exposure to indoor smoky coal emissions that contain polycyclic aromatic hydrocarbons (PAHs). The inflammatory response induced by coal smoke components may promote lung tumor development. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung cancer risk in a population-based case-control study (122 cases and 122 controls) in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% CI: 0.16-0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk globally (false discovery rate value <0.15). In addition, there were positive interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P-interaction = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P-interaction = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes may play a role in the genesis of lung cancer caused by PAH-containing coal smoke. Integrin/receptor and complement pathways as well as IgE regulation are particularly noteworthy.

Mitochondrial DNA content and lung cancer risk in Xuan Wei, China.

Smoky coal contains polycyclic aromatic hydrocarbons (PAHs) and has been strongly implicated in etiology of lung cancer in Xuan Wei, China. While PAHs form bulky adducts in nuclear DNA, they have a 40-90-fold greater affinity for mitochondrial DNA (mtDNA). mtDNA content may increase to compensate for mtDNA damage. We conducted a population-based case-control study of lung cancer in Xuan Wei, China hypothesizing that mtDNA content is positively associated with lung cancer risk. Cases (n=122) and controls (n=121) were individually matched on age (+/-2 years), sex, village of residence, and current fuel type. Lifetime smoky coal use and potential confounders were determined with questionnaires. mtDNA was extracted from sputum and mtDNA content was determined with quantitative PCR. ORs and 95% CIs were calculated with unconditional logistic regression. mtDNA content >157 copies per cell was associated with lung cancer risk (OR=1.8; 95% CI=1.0-3.2) compared with those with

Tuberculosis and subsequent risk of lung cancer in Xuanwei, China.

Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios [HRs] ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.

Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.

Common genetic variation may play an important role in altering lung cancer risk. We conducted a pathway-based candidate gene evaluation to identify genetic variations that may be associated with lung cancer in a population-based case-control study in Xuan Wei, China (122 cases and 111 controls). A total of 1260 single-nucleotide polymorphisms (SNPs) in 380 candidate genes for lung cancer were successfully genotyped and assigned to one of 10 pathways based on gene ontology. Logistic regression was used to assess the marginal effect of each SNP on lung cancer susceptibility. The minP test was used to identify statistically significant associations at the gene level. Important pathways were identified using a test of proportions and the rank truncated product methods. The cell cycle pathway was found as the most important pathway (P = 0.044) with four genes significantly associated with lung cancer (PLA2G6 minP = 0.001, CCNA2 minP = 0.006, GSK3 beta minP = 0.007 and EGF minP = 0.013), after adjusting for multiple comparisons. Interestingly, most cell cycle genes that were associated with lung cancer in this analysis were concentrated in the AKT signaling pathway, which is essential for regulation of cell cycle progression and cellular survival, and may be important in lung cancer etiology in Xuan Wei. These results should be viewed as exploratory until they are replicated in a larger study.

Variation in lung cancer risk by smoky coal subtype in Xuanwei, China.

Lung cancer rates in Xuanwei County have been among the highest in China for both males and females and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with the use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age (+/-2 years) and sex to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was positively and statistically significantly associated with lung cancer risk, when compared with the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore, there was a marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p = 5.17 x 10(-10)). Estimates were highest for coal of the Laibin (OR = 24.8, 95% CI = 12.4-49.6) and Longtan (OR = 11.6, 95% CI = 5.0-27.2) coal types and lower for coal from other subtypes. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source.

Dietary factors, food contamination and lung cancer risk in Xuanwei, China.

BACKGROUND: In rural Xuanwei County, China, the high incidence of lung cancer is attributable largely to burning smoky coal indoors for heating and cooking without adequate ventilation. Such burning generates very high levels of indoor air pollutants, including carcinogenic polycyclic aromatic hydrocarbons, which could contaminate foodstuffs in the home. Thus, residents could be exposed to carcinogenic coal emissions not only via inhalation but also via ingestion of these foodstuffs. METHODS: A population-based case-control study of 498 lung cancer patients and 498 controls was conducted from 1985 through 1990 in Xuanwei. The interviewer-administered study questionnaire queried the frequency of food items commonly consumed in this region. Overall and sex-specific multiple logistic regression models were constructed to estimate Odds ratios (OR) and 95% confidence intervals (CI) for consumption of these foods. RESULTS: Intake of rice, green vegetables, mushrooms and fresh meat was associated with an increased risk of lung cancer. In contrast, intake of corn, buckwheat, radishes, peppers, melons, pickled vegetables, and salt-preserved meats was associated with reduced risk. The detrimental effect of ingesting green vegetables (OR, 2.39; 95% CI, 1.28-4.48) is consistent with previous reports. CONCLUSIONS: These findings suggest that in Xuanwei, food contamination by environmental polycyclic aromatic hydrocarbons may be an important risk factor for lung cancer, and that differential contamination of foods by polycyclic aromatic hydrocarbons possibly explained the different associations with lung cancer risk.

A report of cytokine polymorphisms and COPD risk in Xuan Wei, China.

Indoor air pollution has been documented as an important risk factor for chronic obstructive pulmonary disease (COPD), and inflammation is central to the development and progression of COPD. Single nucleotide polymorphisms (SNP) in some cytokine genes have been reported to be associated with COPD. We examined the association between 18 SNPs in 10 cytokine genes and COPD risk in a case-control study conducted in a population with high exposure to indoor smoky coal emissions. The study included 53 COPD cases and 122 healthy community controls. Carriers of the CSF2 117Ile allele had a 2.4-fold higher risk of COPD than the wild type (Thr/Thr) carriers (OR: 2.44; 95% CI: 1.10-5.41), and the AA genotype at IL8 -351 was associated with an increased risk of COPD (OR: 2.71; 95% CI: 1.04-7.04). When the combined effects of CSF2 117Ile and IL8 -351A were examined, individuals carrying at least one variant in both genes had a five-fold increased risk of COPD (OR: 5.14, 95% CI: 1.32-29.86). This study suggests that polymorphisms in both CSF2 and IL8 may play a role in the pathogenesis of COPD, at least in highly exposed populations. However, in view of our relatively small sample size, this study should be replicated in other populations with substantial exposure to indoor air pollutants such as polycyclic aromatic hydrocarbons (PAH) and particulate matter.

Genotype frequency and F ST analysis of polymorphisms in immunoregulatory genes in Chinese and Caucasian populations.

Selection and genetic drift can create genetic differences between populations. Cytokines and chemokines play an important role in both hematopoietic development and the inflammatory response. We compared the genotype frequencies of 45 SNPs in 30 cytokine and chemokine genes in two healthy Chinese populations and one Caucasian population. Several SNPs in IL4 had substantial genetic differentiation between the Chinese and Caucasian populations (F ST approximately 0.40), and displayed a strikingly different haplotype distribution. To further characterize common genetic variation in worldwide populations at the IL4 locus, we genotyped 9 SNPs at the IL4 gene in the Human Diversity Panel's (N = 1056) individuals from 52 world geographic regions. We observed low haplotype diversity, yet strikingly different haplotype frequencies between non-African populations, which may indicate different selective pressures on the IL4 gene in different parts of the world. SNPs in CSF2, IL6, IL10, CTLA4, and CX3CR1 showed moderate genetic differentiation between the Chinese and Caucasian populations (0.15 < F ST < 0.25). These results suggest that there is substantial genetic diversity in immune genes and exploration of SNP associations with immune-related diseases that vary in incidence across these two populations may be warranted.