Excess Cancer Risk Research Articles

Condensable and filterable particulate matter emission of coal fired boilers and characteristics of PM2.5-bound polycyclic aromatic hydrocarbons in the vicinity

In this research, we simultaneously studied the characteristics of particulate matter-bound PAHs from two industrial coal fire boilers, one highway tunnel, and PAHs from the ambient air of each source. In the stack gas, condensable particulate matter (CPM) was 10–30 times higher than filterable particulate matter (FPM2.5). The content of PAHs in each mg of PM2.5 at emission stack (479 ± 284 ng BaPeq/mg) was reduced by 1.7 times at the industrial vicinity (282 ± 264 ng BaPeq/mg). Inside the tunnel, the PAH content was (138 ± 23.8 ng BaPeq/mg). Such value was reduced with the reduction of human activities from urban (40.8 ± 22.3 ng BaPeq/mg) to rural (34.4 ± 23.9 ng BaPeq/mg) and background areas (3.03 ± 1.94 ng BaPeq/mg). Indeno[1,2,3-cd]pyrene and Benzo[g,h,i]perylene were found to be the major contributor of PAHs from the industrial emission (25–30%) and traffic source (60%). Source apportionment in ambient PAHs found fossil fuel burning (for both industry and traffic purposes), incineration, and biomass burning was major contributors of PAHs in the ambient air in Taiwan. Excessive cancer risk in the vicinity of industrial areas and central regions of Taiwan was higher than the EPA standard threshold of 10−4.

Temporal variability of atmospheric particulate-bound polycyclic aromatic hydrocarbons (PAHs) over central east India: sources and carcinogenic risk assessment.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) are of significant interest owing to their high potential health effects, including mutagenicity and carcinogenicity. We report 16 PAHs measured in ambient PM2.5 from June 2018 to May 2019 over three different sites located in central east India. The annual average PM2.5 mass concentrations of 97.3 ± 18.1 µg m−3, 101.9 ± 19.4 µg m−3, and 93.9 ± 20.3 µg m−3 were measured at RCI (Ranchi), GHY (Gamharia), and BKR (Bokaro), respectively. The mass concentrations at all sampling sites are relatively higher than the annual average concentration of the National Ambient Air Quality Standard. Total annual PAH concentrations (ng m−3) are found to be comparable at BKR (797.9 ± 39.1 ng m−3) and RCI (887.7 ± 38.8 ng m−3); however, a relatively higher average is observed over GHY (1015.1 ± 42.7 ng m−3). Using PAH diagnostic ratios and principal component analysis (PCA), their major sources were attributed to coal and wood combustion as well as vehicular emission of diesel and gasoline at all sampling sites. Significant seasonal variability is observed for PAH composition and mainly attributed to change in emission sources. Summer and winter compositions were found to be impacted by the transport from Indo-Gangetic Plains (IGP). However, ambient level PAHs during the post-monsoon season were impacted by mixed sources from Indo-Gangetic Plain and eastern India. These observations are supported by the analysis of back-trajectory and fire count data. The excess life time cancer risk (ELCR) values estimated for the study sites are within acceptable limits suggesting acceptable risk levels at BKR, GHY, and RCI. This study highlights the significance of ambient aerosol concentration for health risks in the pre-COVID-19 scenario.Graphical

Gastric Mucosal Abnormality and Risk of Pancreatic Cancer: A Population-Based Gastric Biopsy Cohort Study in Sweden.

It remains open whether gastric precancerous lesions are associated with an elevated risk of pancreatic cancer. Our aim was to investigate the association between gastric mucosal status and pancreatic cancer risk. Patients with gastric biopsies [normal, minor changes, superficial gastritis, and atrophic gastritis/intestinal metaplasia/dysplasia (AG/IM/Dys)] from the Swedish histopathology registers during 1979 to 2011 were included. Cross-linkages with several nationwide registries allowed complete follow-up and identification of pancreatic cancer cases until 2014. Standardized incidence ratios (SIR) and HRs were estimated. During 3,438,248 person-years of follow-up with 318,653 participants, 3,540 cases of pancreatic cancer were identified. The same pattern of excess risk of pancreatic cancer compared with the general population was observed across all groups: a peak of 12- to 21-fold excess risk in the first year after biopsy [e.g., normal: SIR = 17.4; 95% confidence interval (CI), 15.7-19.3; AG/IM/Dys: SIR = 11.5; 95% CI, 9.9-13.4], which dropped dramatically during the second and third years, followed by 20% to 30% increased risk after the third year (e.g., normal: SIR = 1.2; 95% CI, 1.1-1.4; AG/IM/Dys: SIR = 1.3; 95% CI, 1.1-1.5). However, no significant excess risk was observed with the normal gastric mucosa as reference. This unique, large pathologic cohort study did not find evidence that abnormal gastric mucosal status is causally associated with a long-term pancreatic cancer risk. However, a highly increased short-term risk was observed for people undergoing gastroscopy with biopsy sampling compared with the general population. Further studies for a long-term risk of pancreatic cancer in patients with gastric biopsies are needed, with further adjustments.

Assessment of Background Radiation, Annual Effective Dose and Excess Lifetime Cancer Risk in Gonabad City

Purpose: Humans are always exposed to ionizing radiation from their environment, which can have destructive effects. This study aimed to measure background gamma radiation and estimate annual effective dose and excess cancer risk in Gonabad city. Materials and Methods: The dose rate due to indoor and outdoor background radiation was measured by RDS-30 radiation survey meter at five zones on the map, including North, South, East, West, and center. Then, the annual effective dose and excess lifetime cancer risk were calculated by associated equations. Results: Mean dose rates for outdoor and indoor spaces were 0.111 µSv/h and 0.139 µSv/h, respectively. The mean background dose rate of indoor space was significantly higher than that of outdoor space. Annual effective dose and excess lifetime cancer risk were obtained as 0.817 and 2.85×10-3, respectively. Conclusion: Background radiation dose, annual effective dose, and cancer risk for Gonabad city were higher than global ones. Further investigations are needed to encompass internal background radiation doses in annual effective dose.

А case of breast cancer in pms2 mutation carrier

Breast cancer (BC) is not a typical manifestation of Lynch syndrome. The existence and extent of excessive breast cancer risk in carriers of pathogenic mutations in the Lynch syndrome-associated genes (MLH1, MSH2, MSH6, PMS2) remains an open question. In addition, it is known that some of the breast neoplasms in patients with this syndrome are causally linked to the hereditary mutation, and some arise completely independently of the hereditary defect in the gene of the DNA mismatch repair system. In the case of accidental detection of such germline mutations in breast cancer patients, a thorough differential diagnosis between these categories of tumors is required, and the result of it is actionable, requiring changes in the management. This is a report of a case of breast cancer that arose in a carrier of a pathogenic mutation in the PMS2 gene, which was an accidental finding. The description of molecular genetic diagnostics is given: the microsatellite markers assessment and the detection of «loss of heterozygosity» allowed to classify the neoplasm in a category of cases that developed without any causal link to the patient's Lynch syndrome.

985Sex differences in the incidence of renal cell carcinoma: results from the EPIC cohort study

Abstract Background Incidence of renal cell carcinoma (RCC) is two-fold higher in men compared with women. This ratio has been remarkably stable, both geographically and over time. We investigated whether established risk factors for RCC can explain the higher incidence in men. Methods 230,399 participants in the EPIC cohort study with complete data for BMI, history of hypertension, and smoking variables were included. Cox regression models with age as the time-scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for sex. Results We identified 690 incident RCC cases. The marginal HR [95% CI] for men versus women was 2.30 [1.98, 2.69]. There was no strong evidence for interactions between hypertension, BMI, or smoking status and sex. Adjusting for BMI, hypertension and smoking variables did not materially affect the estimate (HR: 2.18 [1.85, 2.56]), accounting for only 10% of the observed excess risk. In contrast, smoking factors alone could account for 88% of the observed excess risk of lung cancer for men (marginal HR: 2.19 [2.02, 2.38]; adjusted HR: 1.14 [1.04, 1.25]) Conclusions The two-fold higher incidence of RCC in men compared with women cannot be explained by established risk factors. Key messages Whilst obesity, hypertension, and smoking are established risk factors for RCC, they cannot account for the greater incidence among men compared with women. This indicates the presence of as yet unknown factors to which men are more susceptible than women.

Analysis of Indoor Radon Level and its Health Risks Parameters in Three Selected Towns in Port Harcourt, Rivers State, Nigeria

Analysis of indoor radon level and its health risk parameters has been carried out in Borikiri (BT), Diobu (DR), and Rebisi (RB) towns in Port Harcourt, Rivers State, Nigeria. A pocket sized Corentium Arthings digital radon detector meter was used to record the indoor radon concentration levels. The geographical coordinates were recorded using a hand-held geographical positioning system (GPS) for the various sample points. A total of ten houses were measured for each town making a total of 30 sample points for the three communities. The results obtained show that for Borikiri town, the concentration level varied from 30.7100 - 19.9800 Bqm-3 with an average of 11.32 ± 2.59 Bqm-3 . The annual absorbed dose varied from 7.7478 - 1.1202 mSv/yr with a mean value of 2.59 ± 0.65 mSv/yr while the annual equivalent dose rate varied from 0.829 - 0.336 mSv/yr with an average of 0.69 ± 0.16 mSv/yr The excess life time cancer risk calculated for seventy years (70yrs) varied from 6.510 - 0.941 with an average of 2.45 ± 1.71. The results of the indoor concentration level for Diobu town ranged from 37.74 - 5.9200 Bqm ?3 with a mean value of 12.95 ± 2.91 Bqm-3 . The annual absorbed dose for the area ranged from 9.5214 - 1.1494 with an average of 3.26 ± 0.73 mSv/yr, the annual equivalent dose rate varied from 0.694-0.359 with a mean of 0.78±0.8, the excess life time cancer risk calculated for seventy years ranged from 8.000-1.725 with a mean of 2.91±0.61. The indoor concentration level for Rebisi town ranged from 12.9500?4.0700 Bqm-3 with an average of 8.55 ± 1.00, the annual absorbed dose ranged from 3.2671 - 1.0268 mSv/yr, the annual equivalent dose rate varied from 0.784 - 0.269 with an average of 0.52 ± 0.06, the excess life time cancer risk of 2.745 - 0.863 with an average of 1.82 ± 0.21. The results of the indoor concentration levels, the annual absorbed dose and the annual effective dose rate are all below the ICRP safe limit. However, the results of the excess life time cancer risk are all higher than the ICRP safe standard limit of 0.029 × 10-3 .

Indoor radon measurement in buildings of a university campus in central Iran and estimation of its effective dose and health risk assessment.

Indoor radon is a serious health concern and contributes about 10% of deaths from lung cancer in the USA and Europe. In this study, radon and thoron levels of 20 multi-floor buildings on the campus of Isfahan University of Medical Sciences were measured in cold and hot seasons of a year. SARAD- RTM1688 radon and thoron monitor was used for measurement. The annual effective dose of radon exposure was also estimated for residences on the campus. The results showed that radon concentration was below the WHO guideline (100 Bq m- 3) in most of the buildings. The ranges of radon were from 3 ± 10% to 322 ± 15% Bq m- 3 in winter and from below the detectable level to 145 ± 8% Bq m- 3 in summer. Mostly, the radon concentration in the basement or ground floors was higher than upper floors, however, exceptions were observed in some locations. For thoron, no special trends were observed, and in the majority of buildings, its concentration was below the detectable level. However, in a few locations besides radon, thoron was also measured at a high level during both seasons. The average annual effective dose via radon exposure was estimated to be 0.261 ± 0.339 mSv y- 1. The mean excess lung cancer risk (ELCR) was estimated to be 0.10%. It was concluded that indoor air ventilation, buildings' flooring and construction materials, along with the geological structure of the ground could be the factors influencing the radon concentration inside the buildings. Thus, some applicable radon prevention and mitigation techniques were suggested.

Screening-level assessment of cancer risk associated with ambient air exposure in Aamjiwnaang First Nation

BACKGROUND AND AIM: The manuscript reports findings from a screening-level assessment of cancer risk from outdoor air in and around Aamjiwnaang First Nation. Aamjiwnaang is situated in the Sarnia-Lambton area, which is known for its industrial and petrochemical industry. The area is also known for poor air quality, chemical spills and other environmental events. Residents are concerned about the health impacts of these exposures. Ambient air pollution can contribute to cardiovascular, respiratory diseases, and certain types of cancer. Some communities may be at higher risk to these negative health impacts due to their geographical proximity to pollution sources. METHODS: Outdoor air concentrations were collected from four monitoring stations in the Aamjiwnaang region for known carcinogens benzene and 1,3-butadiene. Air quality data from both current (2015-2016) and historical (1995-1996, 2005-2006) records were examined. Air concentrations were mapped with geographic information systems to assess spatial variations. Outdoor air concentrations were compiled and the Lifetime Excess Cancer Risks (LECR) associated with long-term exposure to known carcinogens were estimated. RESULTS:LECR results for both benzene and 1,3-butadiene were above one per million. The LECR for benzene was 6.4 per million when the Health Canada slope factor was applied and 12.0 when using the US EPA. For 1,3-butadiene the LECR estimate was 8.8 per million. While air quality has improved over time, in 2015-2016 benzene and 1,3 butadiene levels were higher in Aamjiwnaang than provincial averages. Furthermore, benzene levels were above the Ambient Air Quality Criteria target. CONCLUSIONS:We found that ambient air in and around Aamjiwnaang contains a higher annual average concentration of benzene than recommended and may be related to higher cancer risks. This work provides a better understanding of environmental exposures and potential associated cancer risks for residents in the Aamjiwnaang community. This study highlights the need for further air monitoring and a more detailed risk assessment. KEYWORDS: Cancer and cancer-precursors, Risk assessment, Air pollution

Ethyl carbamate in retail market condiments and risk assessment of its dietary exposure for the Korean population

ABSTRACT Ethyl carbamate (EC), a potential human dietary carcinogen, is found in fermented foods including the fermented soybean-based condiments, the major part of the Korean diet. Therefore, it is expected that their EC contents might pose health risks. Herein, we collected 111 condiments and estimated their EC contents via gas chromatography-mass spectrometry. Further, dietary intake of EC was evaluated, and the risk levels were assessed via the margin of exposure (MOE) approach and excess cancer risk assessment. EC contents of the condiments ranged from not detectable to 39.47 μg/kg, and the daily EC exposure ranged from 1.4 to 2.0 ng/kg BW per day, depending on gender and age groups in Korea. Of the condiments, soy sauce was the largest contributor to EC exposure. MOE and excess cancer risks for the average consumer were 166,300 and 9.0 × 10−8, respectively, and those for the consumers in the 95th percentiles (P95) were 53,504 and 2.8 × 10−7, respectively, indicating that the risk of exposure to EC is of lower concern in average consumers than heavy consumers. However, the EC exposure from condiments was higher than that in other Asian countries. Abbreviations: EC: ethyl carbamate; GC-MS: gas chromatography-mass spectrometry; MOE: margin of exposure; MRL: maximum residue level; IDL: instrumental detection level; IQL: instrumental quantification level; MDL: method detection level; MQL: method quantification level; EDI: estimated daily intakes; BMDL10: benchmark dose lower confidence limit

Chemical, microstructural, and biological characterization of wintertime PM2.5 during a land campaign study in a coastal city of eastern India

Bhubaneswar is a rapidly developing city in the eastern coast of India. Previous studies are evidence of the importance of its location for understanding the outflow of pollutants from mainland India into the Bay of Bengal, specifically during the winter. Therefore, we present the characteristics of PM2.5 (particulate matter with aerodynamic diameter < 2.5 μm) collected during a land campaign between November 2014 and January 2015 (representing the winter). Gravimetric measurement of mean PM2.5 was in the range of 101–142 μg/m3 at different locations that was approximately 65–135% higher than the 24 h average National Ambient Air Quality Standards (NAAQS). Spectrometric measurement of PM2.5 and PM1.0 depicted a typical diurnal pattern with distinct morning and evening peaks, confirming similar source contribution and a higher accumulation mode PM over the traffic location. For example, 85.7, 79.1, 80.6, and 84.8 % of PM1.0 contributed to PM2.5 at reference, residential, industrial, and traffic sites, respectively. Chemical characterization and Positive Matrix Factorization (PMF) indicated four most probable sources of PM2.5 with major contributions from vehicular emissions (32.2 %), followed by industrial (25.8 %), combustion (coal, oil, and biomass burning at 22.4 %), and crustal sources (19.7 %). Enrichment factors and mass closure analysis supports this observation. Microstructural analysis broadly classified the PM2.5 particles into four categories. For the first time Endotoxin concentrations in ambient PM2.5 (0.021 ± 0.022 EU/m3) were quantified as a step ahead to understand the biological composition of PM. Heavy metals detected in PM2.5 were used to perform an excess cancer risk assessment.

Assessment of excess lifetime cancer risk and risk of lung cancer due to exposure to radon in a middle eastern city in Iran

ObjectiveTo assess the excess lifetime cancer risk and lung cancer risk due to exposure to 222Rn at homes, stone cutting and processing plants, and stone mines. Methods222Rn concentration was measured in 74 sample sites. Sampling was conducted using Alpha Track, comprising CR-39 polymer film. The detectors were placed at the height of 1.00–1.50 m from the floor and away from windows and sunlight per the US. EPA guidelines. The detectors were retrieved after being exposed to 222Rn for the period of three months and then etched in a 6.25 mol/L NaOH solution at 90 °C for 4 h. The results were used to assess the excess lifetime cancer risk (ELCR) and lung cancer risk (LCR). ResultsThe findings showed that the ELCR at homes, stone cutting and processing plants, and stone mines for the mean levels of 222Rn were 0.49%, 0.15%, and 0.15%, respectively. The ELCR values for all sampling sites were lower than the U.S. EPA action level. The number of lung cancer cases in the Neyriz due to the effective dose received by residents for the mean, maximum, and 95th percentile was estimated to be 1.6, 3.6, and 3.1 per year, respectively. The number of lung cancer cases per 106 population due to exposure to mean concentration for stone cutting and processing plants was 10.53, 15.79, and 14.49, respectively. These values for stone mines were 10.39, 26.76, and 18.87, respectively. The results have shown that LCR values were below the range recommended by ICRP. ConclusionsOverall, the ELCR, because of long-term exposure to 222Rn and its progeny levels, does not pose a significant threat to residents and workers. The LCR associated with radon exposure was low in three sampling sites that could be considered safe for both residents and workers.

Household Air Pollution From Solid Cooking Fuel Combustion and Female Breast Cancer.

Background: Women bear a large share of disease burden caused by household air pollution due to their great involvement in domestic activities. Pollutant emissions are believed to vary by exposure patterns such as cooking and space heating. Little is known about the independent effect of solid cooking fuel combustion on breast cancer risk. We aimed to examine the association of indoor coal and wood combustion for cooking with breast cancer risk.Methods: During June 2004–July 2008, participants aged 30–79 from 10 diverse regions across China were enrolled in the China Kadoorie Biobank. Primary cooking fuel use information in up to three residences was self-reported at baseline. Multivariable logistic regression models yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Results: A total of 290,396 female participants aged 30–79 were included in the main analysis. Compared with long-term clean fuel users, the fully adjusted ORs were 2.07 (95%CI: 1.37–3.13) for long-term coal users, 1.12 (95% CI: 0.72–1.76) for long-term wood users, and 0.98 (95% CI: 0.55–1.74) for those who used mixed solid fuels to cook. Those who had switched from solid to clean fuels did not have an excess risk of breast cancer (OR: 0.88, 95%CI 0.71–1.10).Conclusion: Long-term solid fuel combustion for cooking may increase the risk of breast cancer. The strength of association is stronger among coal users than wood users. Targeted interventions are needed to accelerate the access to clean and affordable energy.

Human health risk assessment in PM10 -bound trace elements, seasonal patterns, and source apportionment study in a critically polluted coking coalfield area of India.

Jharia Coalfield (JCF) has been affected by coalmine fire and subsidence problems for several years. The emission of particulate pollutants is due to the history of unscientific and unregulated coal mining in the JCF area. In the present study (conducted in the year 2019), seasonal variations, possible causes, and human health hazards of particulate matter (PM10 )-bound trace metals like Cd, Cu, Fe, Cr, Ni, Mn, Co, Pb, Zn, and As were estimated. The mean concentration of PM10 (418 ± 67 µg/m3 ) exceeded the limit of NAAQS (National Ambient Air Quality Standards India, 2009) by a factor of 4.18. PM10 -bound trace metal concentrations were found in the order of Fe > Mn > Cu > Zn > Cr > Pb > Co > Ni > Cd > As. The maximum trace metal concentrations of all the metals studied were observed at the mining areas of JCF affected by coalmine fire. Human health carcinogenic and noncarcinogenic risks in children and adults were estimated through exposure pathways, ingestion, dermal contact, and inhalation. The cancer risk was evaluated as excess cancer risk (ECR). Noncancer risk estimates were evaluated as the hazard index (HI) and the hazard quotient (HQ). The HI and HQ values for Cr, Cu, Cd, As, and Pb at coalmine-fire-affected areas were observed to be higher than the value of safe dose (≤1), showing a possible noncarcinogenic risk to the inhabitants as a result of multielemental toxicity. The ECR values (>10-6) in JCF areas suggested a carcinogenic risk to the populace of the area, owing to inhalation of PM10 -linked Cd. Active mine fire (related to mining activities), higher transportation load, and resuspended particulate matter from road transportation were identified as the possible causes of the estimated risks based on principal component analysis and Pearson correlation analyses. Integr Environ Assess Manag 2022;18:469-478. © 2021 SETAC.

Characterization, Sources and Excessive Cancer Risk of PM2.5-Bound Polycyclic Aromatic Hydrocarbons in Different Green Spaces in Lin'an, Hangzhou, China.

PM2.5 samples were collected from residential, commercial, plaza and public green spaces in Lin'an, Hangzhou, in spring (March and April) and winter (February and December) in 2017. PAHs were detected by gas chromatography-mass spectrometry (GC-MS), and their sources were identified using the diagnostic ratio (DR) and principal component analysis-multiple linear regression (PCA-MLR). The average PAH concentration in winter was 1.3 times that in spring (p < 0.01). The PAH concentrations in the green spaces decreased as commercial > residential > plaza > public green space (p < 0.05). The sources of PAHs were vehicle emissions and coal combustion pollution transported by northern Chinese air masses. Slightly higher excessive cancer risks were determined in the commercial and residential green spaces than in the plaza and public green spaces. Green coverage, pedestrian volume, traffic flow and building density greatly influenced the decrease in the PAH concentration in the green spaces. Among the 4 types of green spaces, public green space had the most ecological benefits and should be fully utilized in urban green space planning to improve public health in urban spaces.

Using a hybrid approach to apportion potential source locations contributing to excess cancer risk of PM2.5-bound PAHs during heating and non-heating periods in a megacity in the Middle East

Polycyclic aromatic hydrocarbons (PAHs) represent one of the major toxic pollutants associated with PM2.5 with significant human health and climate effects. Because of local and long-range transport of atmospheric PAHs to receptor sites, higher global attentions have been focused to improve PAHs pollution emission management. In this study, PM2.5 samples were collected at three urban sites located in the capital of Iran, Tehran, during the heating and non-heating periods (H-period and NH-period). The US EPA 16 priority PAHs were analyzed and the data were processed to the following detailed aims: (i) investigate the H-period and NH-period variations of PM2.5 and PM2.5-bound PAHs concentrations; (ii) identify the PAHs sources and the source locations during the two periods; (iii) carry out a source-specific excess cancer risk (ECR) assessment highlighting the potential source locations contributing to the ECR using a hybrid approach.Total PAHs (TPAHs) showed significantly higher concentrations (1.56–1.89 times) during the H-period. Among the identified PAHs compounds, statistically significant periodical differences (p-value < 0.05) were observed only between eight PAHs species (Nap, BaA, Chr, BbF, BkF, BaP, IcdP, and DahA) at all three sampling sites which can be due to the significant differences of PAHs emission sources during H and NH-periods. High molecular weight (HMW) PAHs accounted for 52.7% and 46.8% on average of TPAHs during the H-period and NH-period, respectively. Positive matrix factorization (PMF) led to identifying four main PAHs sources including industrial emissions, petrogenic emissions, biomass burning and natural gas emissions, and vehicle exhaust emissions. Industrial and petrogenic emissions exhibited the highest contribution (19.8%, 27.2%, respectively) during the NH-period, while vehicle exhaust and biomass burning-natural gas emissions showed the largest contribution (40.7%, 29.6%, respectively) during the H-period. Concentration weighted trajectory (CWT) on factor contributions was used for tracking the potential locations of the identified sources. In addition to local sources, long-range transport contributed to a significant fraction of TPHAs in Tehran both during the H- and NH-periods. Source-specific carcinogenic risks assessment apportioned vehicle exhaust (44.2%, 2.52 × 10−4) and biomass burning-natural gas emissions (33.9%, 8.31 × 10−5) as the main cancer risk contributors during the H-period and NH-period, respectively. CWT maps pointed out the different distribution patterns associated with the cancer risk from the identified sources. This will allow better risk management through the identification of priority PAHs sources.

Abstract 822: Can the genetic risk of prostate cancer be attenuated by a healthy lifestyle

Abstract Introduction: Inherited genetic factors contribute significantly to prostate cancer risk and explains 58% of the variability in prostate cancer incidence. It is unclear if the increased genetic risk of prostate cancer, including progression to lethal disease, can be offset by adherence to a healthy lifestyle. Methods: Using a validated polygenic risk score (PRS) for overall prostate cancer, we quantified the genetic risk of prostate cancer in 10,443 men in the Health Professionals Follow-up Study for whom genotype data was available. We applied a validated lifestyle score for lethal prostate cancer (including healthy weight, vigorous physical activity, not smoking, and high consumption of tomatoes, fatty fish, and reduced intake of processed meat) and examined the incidence of overall and lethal (metastatic disease or prostate cancer-specific death) prostate cancer from the date of blood (1993-1999) or cheek collection (2005-2006) through 2014 (2016 for lethal disease). Multivariable Cox proportional hazards models were used to estimate the risk of overall and lethal prostate cancer by joint categories of genetic risk (PRS quartiles) and a time-varying lifestyle score (1-2: least healthy, 3: moderate healthy, and 4-6: most healthy). Both unweighted and inverse probability weighted (IPW) models (to account for possible bias arising from the genotype sampling design) were applied. Lifetime cumulative incidence was estimated using regression standardization. Results: We observed 2,111 prostate cancer and 238 lethal prostate cancer events during a median follow-up of 18 and 22 years, respectively. The PRS enabled risk stratification for both overall and lethal prostate cancer, with men in the highest genetic risk quartile having a 5.4-fold increased risk of overall prostate cancer (HRipw = 5.39, 95% CI = 4.59-6.33) and a 3.5-fold increased risk of lethal prostate cancer (HRipw = 3.53, 95% CI = 2.34-5.32) compared with men in the lowest genetic risk quartile. Among men in the highest genetic risk quartile, adhering to a healthy lifestyle was significantly associated with a decreased risk of lethal prostate cancer (HRipw = 0.54, 95% CI = 0.31-0.94) compared with the least healthy lifestyle. Adhering to healthy lifestyle was not associated with a decreased risk of overall prostate cancer (HRipw = 1.01, 95% CI = 0.84-1.22). In the group of men with highest genetic risk, having a healthy lifestyle at study entry was associated with a lifetime cumulative incidence of lethal prostate cancer of 3%, lower than for men having the least healthy lifestyle (6%) and similar to the population average (3%). Conclusion: In this large prospective cohort of US men, inherited genetic factors increased the risk of both overall and lethal prostate cancer. The associated decreased risk of aggressive disease in those with a favorable lifestyle may suggest that the excess genetic risk of lethal prostate cancer could be offset by adhering to a healthy lifestyle. Citation Format: Anna Plym, Yiwen Zhang, Konrad Stopsack, Bénédicte Delcoigne, Adam S. Kibel, Edward Giovannucci, Kathryn L. Penney, Lorelei A. Mucci. Can the genetic risk of prostate cancer be attenuated by a healthy lifestyle [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 822.

An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality.

Although cancer is traditionally considered a genetic disease, the epigenetic abnormalities, including DNA hypermethylation, histone deacetylation, and/or microRNA dysregulation, have been demonstrated as a hallmark of cancer. Compared with gene mutations, aberrant epigenetic changes occur more frequently, and cellular epigenome is more susceptible to change by environmental factors. Excess cancer risks are positively associated with exposure to occupational and environmental chemical carcinogens, including those from gasoline combustion exhausted in vehicles. Of note, previous studies proposed particulate matter index (PMI) as a measure for gasoline sooting tendency, and showed that, compared with the other molecules in gasoline, 1,2,4–Trimethylbenzene, 2–methylnaphthalene and toluene significantly contribute to PMI of the gasoline blends. Mechanistically, both epigenome and genome are important in carcinogenicity, and the genotoxicity of chemical agents has been thoroughly studied. However, less effort has been put into studying the epigenotoxicity. Moreover, as the blending of ethanol into gasoline substitutes for carcinogens, like benzene, toluene, xylene, butadiene, and polycyclic aromatic hydrocarbons, etc., a reduction of secondary aromatics has been achieved in the atmosphere. This may lead to diminished cancer initiation and progression through altered cellular epigenetic landscape. The present review summarizes the most important findings in the literature on the association between exposures to carcinogens from gasoline combustion, cancer epigenetics and the potential epigenetic impacts of biofuels.

No Excess Risk of Second Malignancies in Chronic Myeloid Leukemia (CML) Patients Treated with Tyrosine Kinase Inhibitors (TKIs)

Introduction With the introduction of tyrosine kinase inhibitors (TKI), the outcomes of patients with chronic myeloid leukemia (CML) has improved dramatically, with the majority of patients in chronic phase achieving near normal life expectancy. As pts live longer on TKIs, they may be more susceptible to subsequent malignancies either as late effects of TKI treatment, or due to genomic instability from having an established hematologic malignancy. Theoretical mechanisms of TKI carcinogenesis include impaired DNA repair mechanisms, inhibition of T-lymphocytes or impaired differentiation of peripheral blood progenitor cells. In this study, we evaluated the risk of subsequent cancers in CML pts at the population level and compared the effect of treatment period (pre- and post-TKI era) on that risk. Methods We used the April 2017 release of all 18 registries of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute to assemble the study cohort. Only patients with CML, not otherwise specified or BCR/ ABL-positive CML were included in the analysis. Patients aged >20 years who had CML as a first cancer diagnosed between January 1973 and December 2013 who developed second cancers (excluding myeloid neoplasms and acute lymphocytic leukemia [to avoid misclassification with CML in blast crisis] and non-melanoma skin cancer) were studied. CML pts with third and subsequent cancers were excluded. Pt and disease characteristics including sex, race and ethnicity, age at diagnosis, year of diagnosis, and year of last follow-up or death were collected. Standardized incidence ratios (SIR) were calculated to assess the risk of a second malignancy by dividing the number of observed second malignancies in CML pts with the number of expected malignancies in the US population, using SEER*Stat. SIRs for the five most common second cancer types were analyzed by treatment eras (1973-1985 [era 1, in which busulfan and hydroxyurea predominated], 1986-2000 [era 2, in which interferon and hematopoietic cell transplantation predominated] and 2001-2014 [era 3, the TKI era] per Blood. 2011; 117(3):755-63 and by age groups (20-39 yrs; 40 -60 yrs and > 60 yrs). Results Of 26,810 patients diagnosed with CML between 1973 and 2014, 1,324 (4.94%) developed a subsequent cancer. The prevalence of second malignancies was 4.59% in era 1, 5.35% in era 2, and 4.84% in era 3 (with the increase from era 1 to 2 likely due to improved capture of cancers and possible transplant effects (BBMT 2007: 13(10):1121-1134)). The most common second cancers in the study period were prostate (17.98%), lung and bronchus (16.01%), breast (8.31%), urinary bladder (5.36%) and non-Hodgkin lymphoma (4.38%) with distribution by treatment era shown in Figure 1. The majority of subsequent malignancies occurred in Caucasians (85.95%), males (61.25%) and in pts > 60 years (68.43%). Table 1 shows SIR of second cancers by treatment eras. In era 1, an excess risk for bladder cancer was observed compared to matched population controls without CML (SIR 2.04, 95% CI 1.14-3.37). In era 2, SIRs for lung cancer and non-Hodgkin lymphoma were marginally elevated [1.34 (95% CI 1.03-1.72) and 1.81 (95% CI 1.01-2.98)], respectively. No excess risk of subsequent cancers was detected in the TKI era. Differences in excess risk of second cancers compared to matched population controls without CML were observed in the study period (1973-2014) when analyzed by age groups, as shown in table 2. Excess risk of oral (SIR 28.46, 95% CI 5.87-83.18) and cervical cancers (SIR 7.61, 95% CI 2.47-17.75) was observed in 20-39 yr age group, melanoma (SIR 1.83, 95% CI 1.02-3.02) in 40-59 yr age cohort, and lung and bronchus (SIR 1.31, 95% CI 1.07-1.58) and non-Hodgkin lymphoma (SIR 2.13, 95% CI 1.43-3.06) in patients >60 yrs. Conclusions In the TKI era of treatment for CML, there does not appear to be an excess risk of second cancers compared to what is seen in matched population controls without CML. Types of second cancers differ by age group. The paucity of second cancers may contribute to the survival of CML patients treated with TKIs approaching that of the general population. Download : Download high-res image (278KB) Download : Download full-size image Disclosures Advani: Pfizer: Consultancy; Takeda/ Millenium: Research Funding. Gerds: CTI BioPharma: Consultancy; Incyte: Consultancy. Maciejewski: Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fees; Apellis Pharmaceuticals: Consultancy; Ra Pharma: Consultancy. Majhail: Sanofi: Honoraria; Anthem, Inc.: Consultancy. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees.

Second Primary Malignancies and Cardiovascular Mortality in Hodgkin disease Survivors — a Surveillance, Epidemiology, and End Results Registry Database Study

BackgroundOver the last few decades there has been significant improvements in survival in patients with Hodgkin disease (HD). But long-term HD survivors, especially those treated with radiation therapy (RT) have an increased risk of second primary malignancy and cardiovascular disease (CVD) related mortality. In this context, we conducted this population based study to analyze trends in CVD related mortality and incidence of lung and thyroid cancer in HD survivors treated with RT.Materials and methodsWe used the Surveillance, Epidemiology, and End Results 9 database to calculate the Standardized Incidence Ratio (SIR) and Excess Absolute Risk (EAR) of lung and thyroid cancer as second primary malignancies in survivors of HD diagnosed between 1973 and 2011, and who were treated with RT. Poisson regression models were used to calculate adjusted incidence of lung and thyroid cancer. We further divided the patients diagnosed with HD during this period into two groups based on if or not they received RT and calculated the mortality due to CVD for each group, by year of diagnosis. Poisson regression models were used to calculate adjusted CVD mortality by year of HD diagnosis for each group. In all three cases, trends in incidence or mortality were evaluated by calculating the Estimated Annual Percentage Change (EAPC) from the regression coefficient for year of diagnosis.ResultsWe identified 11,916 HD cases that received RT from the SEER database, who were followed up for a median duration of 160 months (range - 12 to 480 months). Table 1 provides characteristics of the study population. 319 patients developed lung cancer (SIR of 3.72, 95% CI 3.32 - 4.15; EAR of 13.19 per 10,000 person years at risk) and 86 patients developed thyroid cancer (SIR of 3.67, 95% CI 2.94 - 4.53; EAR of 3.54 per 10,000 person years at risk). Median ages at diagnosis of secondary lung and thyroid cancers were 59 years and 42 years respectively, with median latency periods of 16 years and 17 years respectively. 965 patients among 11,916 patients who received RT died from CVD while the number of CVD deaths was 1,182 among the 12,507 patients who were not administered RT.Using Poisson regression models, we calculated the adjusted incidence of secondary lung cancer and thyroid cancer and the adjusted mortality from CVD, by year of diagnosis. Year of diagnosis, age at diagnosis of HD and latency (time since diagnosis of HD) were the independent variables used in the regression model. Between 1973 and 2011, the adjusted incidence of lung cancer declined at an EAPC of -2.68 (95% CI -13.06 to -3.92) and that of thyroid cancer declined at an EAPC of -3.35 (95% CI -5.73 to -1.00) (Figure 1). Over the same period, CVD mortality per 10,000 person years at risk for patients who received RT declined at an EAPC of -4.34 (95% CI -4.97 to -3.73) and that of patients who did not receive RT declined at an EAPC of -1.92 (95% CI -2.47 to -1.39) (Figure 2).ConclusionWe observed a decline in incidence of lung and thyroid malignancies and CVD mortality in HD survivors over the study period. The decline in CVD mortality over time in patients who received RT was steeper compared to that of patients who did not receive RT. Though our study was limited by the lack of details regarding RT, chemotherapy and comorbidities, these findings are most likely a reflection of recent trends in use of reduced doses and field of RT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.