Association between family history with lung cancer incidence and mortality risk in the Asia Cohort Consortium.

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Association of solid fuel use with cognitive function and the modifying role of lifestyle: A nationwide cohort study in China.

BACKGROUND: As opposed to a healthy lifestyle, indoor air pollution from solid fuel use may be harmful for cognitive function. However, the extent to which lifestyle modifies the association between solid fuel use and cognitive function remains unknown. METHODS: A total of 21,008 individuals aged 16 to 92 were enrolled in 2010 and followed up to 2014 in the China Family Panel Studies (CFPS). Cognitive function was assessed using standardized math and word tests in two waves. Solid fuel use at baseline was assessed by self-reporting of firewood, straw, or coal used for cooking. Lifestyle profile was classified into two groups (favorable vs. unfavorable) based on five modifiable lifestyle factors including alcohol drinking, smoking, body mass index, diet, and physical activity. Linear mixed-effects models were employed to assess the association of solid fuel use and lifestyle with cognitive function. The effect modification of lifestyle was analyzed. RESULTS: A total of 49.7% of the study population used solid fuels for cooking and 17.4% had a favorable lifestyle. Solid fuel use was associated with a significant decrease in cognitive function (ß = -0.29, 95% CI: -0.39, -0.19 for math test; ß = -0.62, 95% CI: -0.84, -0.41 for word test). Lifestyle significantly modified this association (p-interaction: 0.006 for math test; 0.016 for word test), with the corresponding association being less pronounced among participants adhering to a favorable lifestyle compared to those with an unfavorable lifestyle. CONCLUSION: A favorable lifestyle may attenuate the adverse association between solid fuel use and cognitive function. Adopting a favorable lifestyle has the potential to mitigate the adverse neurological effects due to indoor air pollution.

Age at menarche by birth cohort: A pooled analysis of half a million women in Asia.

OBJECTIVES: To evaluate changes in the age at menarche in Asian populations. STUDY DESIGN: Retrospective cohort study. METHODS: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country. RESULTS: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995. CONCLUSIONS: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns.

Exposure to cooking fumes is associated with perturbations in nasal microbiota composition: A pilot study.

Air pollution is one of the leading causes of overall mortality globally. Cooking emissions are a major source of fine particulate matter (PM2.5). However, studies on their potential perturbations on the nasal microbiota as well as their association with respiratory health are lacking. This pilot study aims to assess the environmental air quality among occupational cooks and its associations with nasal microbiota and respiratory symptoms. A total of 20 cooks (exposed) and 20 unexposed controls (mainly office workers), were recruited in Singapore from 2019 to 2021. Information on sociodemographic factors, cooking methods, and self-reported respiratory symptoms were collected using a questionnaire. Personal PM2.5 concentrations and reactive oxygen species (ROS) levels were measured using portable sensors and filter samplers. DNA was extracted from nasal swabs and sequenced using 16s sequencing. Alpha-diversity and beta-diversity were calculated, and between-group variation analysis of species was performed. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between exposure groups and self-reported respiratory symptoms. Higher daily mean PM2.5 (P = 2 × 10-7) and environmental ROS exposure (P = 3.25 × 10-7) were observed in the exposed group. Alpha diversity of the nasal microbiota between the two groups was not significantly different. However, beta diversity was significantly different (unweighted UniFrac P = 1.11 × 10-5, weighted UniFrac P = 5.42 × 10-6) between the two exposure groups. In addition, certain taxa of bacteria were slightly more abundant in the exposed group compared to unexposed controls. There were no significant associations between the exposure groups and self-reported respiratory symptoms. In summary, the exposed group had higher PM2.5 and ROS exposure levels and altered nasal microbiotas as compared to unexposed controls, though further studies are required to replicate these findings in a larger population.

Determinants of residential greenness and its association with prostate cancer risk: A case-control study in Singapore.

BACKGROUND: Exposure to greenness has been shown to be beneficial to health, but few studies have examined the association between residential greenness and prostate cancer (PCa) risk. Our main objectives were to identify the determinants of residential greenness, and to investigate if residential greenness was associated with PCa risk in Singapore. METHODS: The hospital-based case-control study was conducted between April 2007 and May 2009. The Singapore Prostate Cancer Study (SPCS) comprised 240 prostate cancer cases and 268 controls, whose demographics and residential address were collected using questionnaires. Residential greenness was measured by normalized difference vegetation index (NDVI) around the participants' homes using a buffer size of 1 km. Determinants of NDVI were identified using a multivariable linear regression model. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of associations between NDVI and PCa risk, adjusting for potential confounders. RESULTS: Having a BMI within the second quartile, as compared to the lowest quartile, was associated with higher levels of NDVI (ß-coefficient = 0.263; 95% CI = 0.040-0.485) after adjusting for covariates. Additionally, being widowed or separated, as compared to being married, was associated with lower levels of NDVI (ß-coefficient = -0.393; 95% CI = -0.723, -0.063). An interquartile range (IQR) increase in NDVI was positively associated with prostate cancer risk OR = 1.45; 95% CI = 1.02-2.07). Stratified analysis by tumour grade and stage showed that higher NDVI was associated with higher risk of low grade PCa. CONCLUSION: Our findings suggested that residential greenness was associated with higher risk of PCa in Singapore. Future studies on the quality and type of green spaces, as well as other factors of residential greenness, in association with PCa risk should be conducted to better understand this relationship.

Association between diesel exhaust exposure and mitochondrial DNA methylation.

OBJECTIVES: Diesel exhaust is an established human carcinogen, however the mechanisms by which it leads to cancer development are not fully understood. Mitochondrial dysfunction is an established contributor to carcinogenesis. Recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis. In this study, we aim to evaluate the association between diesel engine exhaust (DEE) exposure with mitochondrial DNA (mtDNA) methylation levels in workers exposed to DEE. METHODS: The study population consisted of 53 male workers employed at a diesel engine manufacturing facility in Northern China who were routinely exposed to diesel exhaust in their occupational setting, as well as 55 unexposed male control workers from other unrelated factories in the same geographic area. Exposure to DEE, elemental carbon, organic carbon, and particulate matter (PM2.5) were assessed. mtDNA methylation for CpG sites (CpGs) from seven mitochondrial genes (D-Loop, MT-RNR1, MT-CO2, MT-CO3, MT-ATP6, MT-ATP8, MT-ND5) was measured in blood samples. Linear regression models were used to estimate the associations between DEE, elemental carbon, organic carbon and PM2.5 exposures with mtDNA methylation levels, adjusting for potential confounders. RESULTS: DEE exposure was associated with decreased MT-ATP6 (difference = -35.6%, P-value = 0.019) and MT-ATP8 methylation (difference = -30%, P-value = 0.029) compared to unexposed controls. Exposures to elemental carbon, organic carbon, and PM2.5 were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05). CONCLUSIONS: Our findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.

Secondhand smoke in the densely populated urban setting: A cross-sectional survey of exposure, knowledge, attitudes, and respiratory symptoms.

Secondhand smoke (SHS) remains a common health threat in densely populated, urban settings. We estimated the prevalence of exposure and associated respiratory symptoms, knowledge, attitudes, and behaviors in a multi-ethnic, weighted sample of Singapore residents using a cross-sectional survey of 1806 adults. We weighted data to match the national population in terms of gender, ethnicity, and education level and analyzed data using descriptive statistics, bivariate analyses, multiple linear and logistic regressions, and a multinomial logistic regression model. About 88% of respondents reported regular SHS exposure. Nearly 57% reported exposure to neighbors' SHS at home. Respiratory symptoms were reported by 32.5% and significantly associated with exposure to daily (AOR = 2.63, 95% CI = 1.62-4.36), non-daily (AOR = 1.75, 95% CI = 1.14-2.77), and neighbors' (AOR = 1.37, 95% CI = 1.07-1.76) SHS. More knowledge of SHS was associated with male gender (ß = 0.28, p = 0.0009) and higher household income (linear trend; p = 0.0400). More negative attitudes to SHS were associated with older age (linear trend; p < 0.0001). Engaging in behaviors to avoid SHS was associated with a more negative attitude to SHS (AOR = 1.09-1.23). SHS exposure is common in Singapore's densely populated setting and associated with respiratory symptoms, even if exposure is non-daily or from neighboring homes.

Association between previous lung diseases and lung cancer risk: a systematic review and meta-analysis.

Previous lung diseases (PLD) are known risk factors for lung cancer. However, it remains unclear how the association varies by lung cancer subtype and socio-demographic characteristics. We conducted a systematic literature search in three electronic databases from the inception of each database up until 13 January 2021. A total of 73 studies (18 cohort and 55 case-control studies) consisting of 97 322 cases and 7 761 702 controls were included. Heterogeneity was assessed using the I2 statistic. Based on the heterogeneity, either the fixed-effects or random-effects model was used to estimate the pooled summary estimate (PSE) and 95% confidence interval (CI) for the association between PLD and lung cancer risk. A history of asthma, chronic bronchitis, emphysema, pneumonia, tuberculosis, and chronic obstructive pulmonary disease (COPD) was associated with higher lung cancer risk, with a history of COPD and emphysema having at least twofold relative risk. A history of hay fever was associated with lower lung cancer risk (PSE= 0.66, 95% CI= 0.54-0.81), particularly among ever-smokers (PSE= 0.55, 95% CI= 0.41-0.73). Individuals with a diagnosis of asthma, emphysema, or pneumonia within 1-10 years prior to lung cancer diagnosis were observed to have a higher lung cancer risk as compared to those who were diagnosed more than 10 years prior to lung cancer diagnosis. Ever-smokers with a history of COPD or emphysema were observed to have at least twofold relative risk of lung cancer compared to those without this history. Due to the observed association between PLD with higher risk of lung cancer, it is advisable that individuals with PLD should be closely monitored and prioritised for lung cancer screening.

Association between air quality, meteorological factors and COVID-19 infection case numbers.

The coronavirus disease (COVID-19) has become a global pandemic affecting many countries, including Singapore. Previous studies have investigated the relationship of air pollutant levels and meteorological factors with respiratory disease risk and hospital admission rates. However, associations between air pollutant concentrations and meteorological factors with COVID-19 infection have been equivocal. This study aimed to assess the association between core air pollutant concentrations, meteorological variables and daily confirmed COVID-19 case numbers in Singapore. Data on air pollutant levels (particulate matter [PM2.5, PM10], ozone [O3], carbon monoxide [CO], nitrogen dioxide [NO2], sulphur dioxide [SO2], pollutant standards index [PSI]) and meteorological factors (rainfall, humidity, temperature) was obtained from the Singapore National Environment Agency (NEA) from January 23, 2020 to April 6, 2020. The daily reported COVID-19 case numbers were retrieved from the Singapore Ministry of Health (MOH). Generalized linear models with Poisson family distribution and log-link were used to estimate the model coefficients and 95% confidence intervals (CIs) for the association between air pollutant concentrations and meteorological factors (8-day and 15-day moving averages (MA)) with COVID-19 case numbers, adjusting for humidity, rainfall and day of week. We observed significantly positive associations between NO2, PSI, PM2.5 and temperature with COVID-19 case numbers. Every 1-unit increase (15-day MA) in PSI, 1 µg/m3 increase (15-day MA) in PM2.5, NO2 and 0.1 °C increase in temperature were significantly associated with a 35.0% (95% CI: 29.7%-40.5%), 22.6% (95% CI: 12.0%-34.3%), 34.8% (95% CI: 29.3%-40.4%) and 28.6% (95% CI: 25.0%-32.4%) increase in the average daily number of COVID-19 cases respectively. On the contrary, PM10, O3, SO2, CO, rainfall and humidity were significantly associated with lower average daily numbers of confirmed COVID-19 cases. Similar associations were observed for the 8-day MAs. Future studies could explore the long-term consequences of the air pollutants on COVID-19 infection and recovery.

Behavioral impact of national health campaigns on healthy lifestyle practices among young adults in Singapore: a cross-sectional study.

BACKGROUND: National health campaigns are often used to improve lifestyle behaviors in the general population. However, evidence specifically in the young adult population is scarce. Given the general deterioration of healthy lifestyle practices from adolescence to young adulthood, it is imperative to study this age group. This study aimed to investigate the behavioral impact of a national health campaign in Singapore on the lifestyle practices of young adults, and whether sex or full-time working and schooling status affected lifestyle practices. METHODS: A total of 594 Singaporean respondents aged 18-39 years old were interviewed via a cross-sectional study in December 2019. Lifestyle practices assessed were diet, exercise, alcohol consumption, current tobacco use, and participation in health screening programs. Other factors investigated included exposure to the national health campaign "War on Diabetes" (WoD), sex, ethnicity, and working/schooling status. Multivariable modified Breslow-Cox proportional hazards models were used to estimate prevalence risk ratios (PRRs) as measures for the associations in this study, after adjusting for potential confounders. RESULTS: Exposure to the WoD campaign had a significant association with meeting dietary recommendations (PRR = 1.6, 95% CI: 1.0-2.5, p = 0.037), participation in screening (PRR = 1.2, 95% CI: 1.0-1.5, p = 0.028), and current tobacco use (PRR = 0.5, 95% CI: 0.3-0.8, p = 0.003). Males were significantly more likely to meet exercise recommendations (PRR = 2.0, 95% CI: 1.5-2.7, p < 0.001), currently use tobacco (PRR = 3.9, 95% CI: 2.2-6.9, p < 0.001), and consume alcohol excessively (PRR = 1.5, 95% CI: 1.0-2.3, p = 0.046), as compared to females. Working young adults were significantly less likely to meet exercise recommendations (PRR = 0.7, 95% CI: 0.5-0.9, p = 0.019) but significantly more likely to be current tobacco users (PRR = 1.8, 95% CI: 1.1-3.1, p = 0.024), as compared to those who were in school. CONCLUSIONS: While this paper affirms that national health campaigns have significant beneficial associations in diet, health screenings and current tobacco use, policymakers should acknowledge that young adults are an age group with different influences that impact their healthy lifestyle habits. Specific interventions that target these subgroups may be required for better health outcomes. Future studies should evaluate other socio-environmental factors that could play a role in modifying the effect of health campaigns among young adults.

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

Associations between tea and coffee beverage consumption and the risk of lung cancer in the Singaporean Chinese population.

BACKGROUND: Tea and coffee are widely consumed beverages. Tea flavonoids have been shown to inhibit lung tumorigenesis using in vitro and in vivo models. Conversely, coffee contains complex mixtures of biochemically active compounds, some of which may have genotoxic and mutagenic properties. However, previous epidemiologic studies have shown inconsistent results on tea and coffee in relation to lung cancer risk. METHODS: The Singapore Chinese Health Study is a population-based prospective cohort of 63,257 Singaporean Chinese men and women, with an average of 17.7 years of follow-up. Information on tea and coffee consumption and other lifestyle factors was collected through in-person interviews at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders. RESULTS: There were 1486 incident lung cancer cases. Compared to non-daily coffee drinkers, HRs (95% CIs) of lung cancer risk for those consuming one, two, and three or more cups of coffee per day were 1.18 (1.02-1.36), 1.21 (1.05-1.40), and 1.32 (1.08-1.62) respectively (P for trend = 0.0034). The highest category of black tea consumption (at least 2 cups per day) was inversely associated with risk of lung cancer [HR (95% CI) = 0.73 (0.53-0.99)], particularly among men [HR (95% CI) = 0.67 (0.47-0.95)], compared to less-than-weekly black tea drinkers, although the interaction by sex was not statistically significant. CONCLUSIONS: Coffee beverage consumption was associated with higher risk of developing lung cancer. On the other hand, black tea intake was associated with lower risk of lung cancer among men in our cohort, and further studies are needed to confirm this association.

Reproductive factors and lung cancer risk: a comprehensive systematic review and meta-analysis.

BACKGROUND: A number of studies have investigated the association between reproductive factors and lung cancer risk, however findings are inconsistent. This meta-analysis aimed to evaluate the association between female reproductive factors and lung cancer risk. METHODS: We conducted a comprehensive systematic search to identify relevant and eligible studies published before 18th December 2019. Inter-study heterogeneity was assessed using the Q test and I2 statistic. Based on the heterogeneity of each reproductive factor, fixed or random effects models were used to calculate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses by study design, lung cancer subtypes, smoking status, and ethnicity were also performed. RESULTS: A total of 66 studies with 20 distinct reproductive factors were included in this meta-analysis. Comparing the highest and lowest categories (reference) of each reproductive factor, parity (OR = 0.83, 95% CI = 0.72-0.96), menstrual cycle length (OR = 0.79, 95% CI = 0.65-0.96), and age at first birth (OR = 0.85, 95% CI = 0.74-0.98), were significantly associated with a lower risk of overall lung cancer. On the contrary, non-natural menopause was significantly associated with higher lung cancer risk (OR = 1.52, 95% CI = 1.25-1.86). Among never-smokers, a significant negative association was found between parity and lung cancer risk. Both parity and non-natural menopause were statistically significant in case-control studies. CONCLUSION: These results suggest that certain reproductive factors may be associated with lung cancer risk. Future studies should further validate the associations, and investigate the underlying mechanisms.

Lung cancer risk by geologic coal deposits: A case-control study of female never-smokers from Xuanwei and Fuyuan, China.

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous ("smoky") coal for heating and cooking. We conducted a population-based case-control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43-16.38) to OR = 33.40 (95% CI: 13.07-85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61-25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03-11.04, pdifference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

Household coal combustion, indoor air pollutants, and circulating immunologic/inflammatory markers in rural China.

The study aim was to investigate whether household bituminous ("smoky") coal use and personal exposure to combustion emissions were associated with immunologic/inflammatory marker levels. A cross-sectional study of healthy never-smoking women from rural Xuanwei and Fuyuan, China was conducted, which included 80 smoky coal and 14 anthracite ("smokeless") coal users. Personal exposure to fine particulate matter (PM2.5) and benzo[a]pyrene (BaP) was assessed using portable devices, while 67 circulating plasma immunologic/inflammatory markers were measured using multiplex bead-based assays. Multivariable linear regression models were employed to estimate associations between smoky coal versus smokeless coal use, indoor air pollutants, and immunologic/inflammatory markers. Six markers were altered among smoky coal users compared to smokeless coal, including significantly decreased interferon-inducible T-cell alpha chemoattractant (CXCL11/I-TAC), and increased serum amyloid P component (SAP). CXCL11/I-TAC was previously found to be reduced in workers exposed to high levels of diesel engine exhaust, which exhibits similar constituents as coal combustion emissions. Further, there was evidence that elevated PM2.5 and BaP exposure was associated with significantly diminished levels of the serum amyloid A (SAA); however, the false discovery rates (FDRs) were >0.2 after accounting for multiple comparisons. Inflammatory processes may thus mediate the carcinogenic effects attributed to smoky coal emissions.

HOXA9 is a novel myopia risk gene.

PURPOSE: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-ß that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. METHODS: The Singapore GUSTO birth cohort provides data on children's cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. RESULTS: A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-ß, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. CONCLUSION: Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.

Serologic markers of viral infection and risk of non-Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore.

Incidence rates of non-Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre-diagnostic blood and NHL risk in East Asians. We conducted a nested case-control study of 214 NHL cases and 214 matched controls from three population-based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead-based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA-D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10-3.81; ptrend = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96-4.89; ptrend = 0.008) Epstein-Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus-6 (HHV-6) antigen (OR = 1.85, 95% CI = 1.04-3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV-HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV-6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.