Cancer and industrial activities in China

Associations between pollution and life expectancy, infant mortality, and cardiorespiratory disease are documented in China. Yet, less is known about environmental drivers of Chinese cancers. Here, we systematically link polluting industrial activity to cancer incidence, cancer mortality, and cancer cluster designations. We investigate county-level associations between industrial production and age-adjusted incidence and mortality reported in official cancer registries. We then combine the locations of roughly 3 million enterprises with administrative data from roughly 600,000 villages and cancer cluster documentation from 380 villages. We show that county-level value-added from industry is associated with age-adjusted incidence and mortality for all cancers; bronchus, trachea, and lung cancers; stomach cancers; and esophageal cancers. We show that the odds that a village contains a documented cancer cluster increase 3-4 times if the village contains a pollution-intensive industrial facility. Leather, chemical, and dye enterprises appear to drive results. All else equal, smaller facilities increase the odds of cancer clusters.

Cancer cluster among small village residents near the fertilizer plant in Korea

Objectives In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001–2017) and whether living in the village was associated with a higher risk of cancer. Methods Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. Results Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. Conclusions The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation.

A Cluster-Based Approach for Identifying Prognostic microRNA Signatures in Digestive System Cancers

Cancer remains the second leading cause of death all over the world. Aberrant expression of miRNA has shown diagnostic and prognostic value in many kinds of cancer. This study aims to provide a novel strategy to identify reliable miRNA signatures and develop improved cancer prognostic models from reported cancer-associated miRNAs. We proposed a new cluster-based approach to identify distinct cluster(s) of cancers and corresponding miRNAs. Further, with samples from TCGA and other independent studies, we identified prognostic markers and validated their prognostic value in prediction models. We also performed KEGG pathway analysis to investigate the functions of miRNAs associated with the cancer cluster of interest. A distinct cluster with 28 cancers and 146 associated miRNAs was identified. This cluster was enriched by digestive system cancers. Further, we screened out 8 prognostic miRNA signatures for STAD, 5 for READ, 18 for PAAD, 24 for LIHC, 12 for ESCA and 18 for COAD. These identified miRNA signatures demonstrated strong abilities in discriminating the overall survival time between high-risk group and low-risk group (p-value < 0.05) in both TCGA training and test datasets, as well as four independent Gene Expression Omnibus (GEO) validation datasets. We also demonstrated that these cluster-based miRNA signatures are superior to signatures identified in single cancers for prognosis. Our study identified significant miRNA signatures with improved prognosis accuracy in digestive system cancers. It also provides a novel method/strategy for cancer prognostic marker selection and offers valuable methodological directions to similar research topics.

Spatio-temporal mapping of breast and prostate cancers in South Iran from 2014-2017

Background:The most common gender-specific malignancies are cancers of the breast and the prostate. In developing countries, cancer screening of all at risk is impractical because of healthcare resource limitations. Thus, determining high-risk areas might be an important first screening step. This study explores incidence patterns of potential high-risk clusters of breast and prostate cancers in southern Iran.Methods:This cross-sectional study was conducted in the province of Kerman, South Iran. Patient data were aggregated at the county and district levels calculating the incidence rate per 100,000 people both for cancers of the breast and the prostate. We used the natural-break classification with five classes to produce descriptive maps. A spatial clustering analysis (Anselin Local Moran’s I) was used to identify potential clusters and outliers in the pattern of these cancers from 2014 to 2017.Results:There were 1,350 breast cancer patients (including, 42 male cases) and 478 prostate cancer patients in the province of Kerman, Iran during the study period. After 45 years of age, the number of men with diagnosed prostate cancer increased similarly to that of breast cancer for women after 25 years of age. The age-standardised incidence rate of breast cancer for women showed an increase from 29.93 to 32.27 cases per 100,000 people and that of prostate cancer from 13.93 to 15.47 cases per 100,000 during 2014-2017. Cluster analysis at the county level identified high-high clusters of breast cancer in the north-western part of the province for all years studied, but the analysis at the district level showed high-high clusters for only two of the years. With regard to prostate cancer, cluster analysis at the county and district levels identified high-high clusters in this area of the province for two of the study years.Conclusions:North-western Kerman had a significantly higher incidence rate of both breast and prostate cancer than the average, which should help in designing tailored screening and surveillance systems. Furthermore, this study generates new hypotheses regarding the potential relationship between increased incidence of cancers in certain geographical areas and environmental risk factors.

Spatio-temporal mapping of breast and prostate cancers in South Iran from 2014 to 2017

Background The most common gender-specific malignancies are cancers of the breast and the prostate. In developing countries, cancer screening of all at risk is impractical because of healthcare resource limitations. Thus, determining high-risk areas might be an important first screening step. This study explores incidence patterns of potential high-risk clusters of breast and prostate cancers in southern Iran. Methods This cross-sectional study was conducted in the province of Kerman, South Iran. Patient data were aggregated at the county and district levels calculating the incidence rate per 100,000 people both for cancers of the breast and the prostate. We used the natural-break classification with five classes to produce descriptive maps. A spatial clustering analysis (Anselin Local Moran’s I) was used to identify potential clusters and outliers in the pattern of these cancers from 2014 to 2017. Results There were 1350 breast cancer patients (including, 42 male cases) and 478 prostate cancer patients in the province of Kerman, Iran during the study period. After 45 years of age, the number of men with diagnosed prostate cancer increased similarly to that of breast cancer for women after 25 years of age. The age-standardised incidence rate of breast cancer for women showed an increase from 29.93 to 32.27 cases per 100,000 people and that of prostate cancer from 13.93 to 15.47 cases per 100,000 during 2014–2017. Cluster analysis at the county level identified high-high clusters of breast cancer in the north-western part of the province for all years studied, but the analysis at the district level showed high-high clusters for only two of the years. With regard to prostate cancer, cluster analysis at the county and district levels identified high-high clusters in this area of the province for two of the study years. Conclusions North-western Kerman had a significantly higher incidence rate of both breast and prostate cancer than the average, which should help in designing tailored screening and surveillance systems. Furthermore, this study generates new hypotheses regarding the potential relationship between increased incidence of cancers in certain geographical areas and environmental risk factors.

Spatio-temporal mapping of breast and prostate cancers in South Iran from 2014-2017

Background:The most common gender-specific malignancies are cancers of the breast and the prostate. In developing countries, cancer screening of all at risk is impractical because of healthcare resource limitations. Thus, determining high-risk areas might be an important first screening step. This study explores incidence patterns of potential high-risk clusters of breast and prostate cancers in southern Iran.Methods:This cross-sectional study was conducted in the province of Kerman, South Iran. Patient data were aggregated at the county and district levels calculating the incidence rate per 100,000 people both for cancers of the breast and the prostate. We used the natural-break classification with five classes to produce descriptive maps. A spatial clustering analysis (Anselin Local Moran’s I) was used to identify potential clusters and outliers in the pattern of these cancers from 2014 to 2017.Results:There were 1,350 breast cancer patients (including, 42 male cases) and 478 prostate cancer patients in the province of Kerman, Iran during the study period. After 45 years of age, the number of men with diagnosed prostate cancer increased similarly to that of breast cancer for women after 25 years of age. The age-standardised incidence rate of breast cancer showed an increase from 29.93 to 32.27 cases per 100,000 people and that of prostate cancer from 13.93 to 15.47 cases per 100,000 during 2014-2017. Cluster analysis at the county level identified high-high clusters of breast cancer in the north-western part of the province for all years studied, but the analysis at the district level showed high-high clusters for only two of the years. With regard to prostate cancer, cluster analysis at the county and district levels identified high-high clusters in this area of the province for two of the study years.Conclusions:North-western Kerman had a significantly higher incidence rate of both breast and prostate cancer than the average, which should help in designing tailored screening and surveillance systems. Furthermore, this study generates new hypotheses regarding the potential relationship between increased incidence of cancers in certain geographical areas and environmental risk factors.

Cancer cluster and citizen alarms: epidemiological and statistical approaches

Background Respond to alarms for possible cancer cluster is a public health problem, but the management of these alarms is difficult and sometime conflictual. Methods We reviewed the guidelines on the management of disease clusters developed in various countries and the approaches used in previous disease cluster episodes in Tuscany. Statistical approaches for cluster detection were also reviewed. We performed a clustering analysis (spatio or spatio-temporal when appropriate) on childhood leukemia using data from Tuscany Cancer Registry (RTT). We used spatial hierarchical Bayesian model on aggregate data at municipality level. We performed test for general clustering and cluster detection on individual data. Results More than 100 tests for clustering analysis has been identified in the literature. Bayesian analysis on aggregate data did not show areas at higher risk with the exception of the city of Florence for childhood cancer among males. We did not found clusters for leukemia. In previous studies on disease clusters in Tuscany, most investigations have been started from community concerns and in the majority of situations a multidisciplinary approach was used. In some case an increase of incidence rate was observed, but rarely specific cluster cancer tests were used. Conclusions Hierarchical Bayesian models to aggregate data provided useful to identify long range geographical patterns while clustering analysis on individual data is a useful tool for small scale patterns. Both represent important tools for epidemiological surveillance studies particularly on childhood cancer. The best test for all situations doesn't exist, but the choice is determined by the type of question being asked from the data, by different situations and by different approaches. The Tuscany cancer clusters survey and the review of the guidelines on the management of clusters developed in different countries, give us the opportunity to formulate some suggestions for the health agencies. Key messages Respond to alarms for cluster of cancer and suggest recommendations for epidemiological and statistical standardized approaches is a public health issue. Tuscany cancer clusters survey and the review of the guidelines on the management of clusters developed in different countries, give the opportunity to formulate some suggestions for health agencies.

Assessing the variations in breast/ovarian cancer risk for Chinese BRCA1/2 carriers

Background: Cancer risks vary in different BRCA1/2 mutations. Previous studies based on Caucasian population have identified regions associated with elevated/reduced risks of breast/ovarian cancers. Since ethnic differences are known to affect BRCA1/2 mutation spectra, we are interested in defining Chinese-specific ovarian/breast cancer cluster regions (OCCR/BCCR) and comparing with previously reported Caucasian-based cluster regions. We also aim to characterize the distribution and estimate the cancer risks of different Chinese recurrent mutations. Methods: 7,919 (3,641 unselected cancer-free women + 4,278 female cancer patients) individuals were included in the study. Germline BRCA1/2 status were detected with amplicon-based next-generation sequencing. BRCA1/2 carriers were defined as bearing likely pathogenic or pathogenic mutations. We calculated odds ratio (OR) of breast cancer and OR of ovarian cancer, and their ratio of the two ORs (ROR) for each region. ROR > 1 indicated elevated odds of breast cancer and/or decreasing odds of ovarian cancer; ROR < 1 indicated increasing odds of ovarian cancer and/or decreasing breast cancer odds. The frequency, distribution and penetrance of six known Chinese founder mutations were characterize respectively. Haplotype analysis and age estimation were performed on the most prevalent and widely-spread founder mutation BRCA1:c.5470_5477del. Results: A total of 729 subjects were detected with germline BRCA1/2 deleterious mutations, including 236 BRCA1 and 122 BRCA2 mutations. The putative Chinese OCCR/BCCR are partially overlapped with Caucasian-based OCCR/BCCR and shared structural-functional characteristics. The six known Chinese founder mutations vary greatly in both distribution and penetrance. The two most prevalent and widely-spread mutations are estimated to convey low penetrance, while the area-restricted founder mutations seemed to confer higher or nearly complete penetrance. The most prevalent founder mutation BRCA1:c.5470_5477del accounting for 9.5% - 18% of BRCA1 carriers is estimated to have emerged ~2,090 years ago (70 B.C.) during the Han Dynasty, about 290 years (~14.5 generations) prior to the Three Kingdoms Period when a major population migration occurred. Conclusion: BRCA1/2 carriers with different genotypes have significantly different cancer risks. Hence ideally risk assessment should be mutation-specific, rather than concerning a single figure. The probably most ancient Chinese founder mutation may have originated more than 2,000 years ago.