Excess Cancer Risk Research Articles

Risk of cancer in young and middle‐aged adults with childhood‐onset type 1 diabetes in Sweden—A prospective cohort study

In persons with type 1 diabetes, the risk of cancer remains controversial. We wanted to examine the excess risk of cancer in a large population-based cohort diagnosed with type 1 diabetes before 15years of age. From 1July 1977 to 31 December 2013, we prospectively and on a national scale included 18,724 persons (53% men) with childhood-onset type 1 diabetes. For each person with type 1 diabetes, we selected four referents, matched for the date at birth and municipality of living at the time when the case developed diabetes. Cases and referents were linked to national registers of cancer and of the cause of death. A total of 125 persons (61% women) with diabetes had 135 different cancers, all diagnosed after the diabetes diagnosis. The median duration from diabetes diagnosis to first cancer diagnosis was 19years (interquartile range 10-26). The median age at cancer diagnosis in the diabetes group was 28years (interquartile range 20-35). The overall standardized incidence ratio (95%), using the Swedish general population as referents for women with diabetes was 1.28 (1.02, 1.58) and when comparing women with diabetes with matched referents, we found a hazard ratio of 1.42 (1.10, 1.85). No elevated risk was seen for men. Cancers of the breast and testis were the most common types in women and men respectively. Women with childhood-onset type 1 diabetes had a small but significantly elevated risk of cancer. No such tendency was seen for men. The reason behind this is unclear.

Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses.

Background:The detrimental health effects associated with the receipt of moderate (0.1–1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood.Methods and findings:We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia.Conclusions:Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero, at about 0.02 Gy.

Assessment on Radiation Hazard Indices from Selected Dumpsites in Lafia Metropolis, Nasarawa State, Nigeria

This research reports an assessment of ionizing radiation in some chosen Dumpsites in Lafia Local government area of Nasarawa State. Ionizing radiation measurement was conducted at four Dump sites. The survey was done using a radiation survey meter (Radex one Outdoor 55130719 NA). Radiation exposure rate in micro sievert per hour (μSvhr-1) was measured. Readings were taken by placing the detector at gonad level about 1 meter above the ground. Result showed that the average annual effective dose rate in the selected dumpsites were 0.22 mSv/yr for Lafia modern market, 0.17 mSv/yr for dumpsite opposite governor Isa house, 0.15 mSv/yr for Timber shade Lafia and 0.20 mSv/yrfor Science School Lafia respectively with a mean value of 0.19 mSv/yr for all location, while the mean calculated excess life cancer risk (ELCR) is 0.65 x 10-3.Dumpsites yearly absorbed dose rate and their corresponding ELCR values did not exceed the 1.0 mSv/y Basic Safety Standard set for the masses by International Council on Radiation Protection (ICRP, 1999) and mean world average ECLR value of 1.16 x 10-3. Based on these results there are no radiation consequence to the scavengers, dumpsite workers and residents living around the dumpsites.

Evaluation of natural radioactivity level in Delanta-Dawunt, Wollo District, Ethiopia

ABSTRACT In the Delanta-Dawunt district of Ethiopia’s northern eastern Amhara region, twenty-one different environmental samples (gemstones) were gathered. This is one of the opal-mining (gemstone) locations in Ethiopia. We divided the 21 obtained samples into seven groups. The study’s major goals were to quantify the activity concentration of gemstones (opals) and examine the health implications. For 226Ra, the activity concentration ranged from 11.97 ± 2.46 to 62.44 ± 14.99 Bq kg−1, 25.69 ± 3.69 to 137.84 ± 13.23 Bq kg−1 for 232Th, and 184.84 ± 3.59 to 968.56 ± 18.16 Bq kg−1 for 40K. 226Ra, 232Th, and 40K were found to have mean radioactivity concentrations of 29.84 ± 6.53, 68.44 ± 18.94, and 390.87 ± 6.09 Bq kg−1, respectively. Radium equivalent activity (Raeq), absorbed dose, annual effective dose equivalent, external and internal radiation hazard (Hex and Hin) index, and activity utilisation index have mean values of 151.68 19.46 Bq kg−1, 72.19 8.48 nGy h−1, 0.07 0.01mSv y−1, 0.43, 0.51, 0.57 0.08, and 0.29 0.03. 232Th has higher specific activity than the global average, while 40K has the same. Meanwhile, the absorbed dose is higher than the world’s means value. The average value of excess life cancer risk found in this study is the same as the world’s average value.

Cancer risk following low doses of ionising radiation – Current epidemiological evidence and implications for radiological protection

Recent studies suggest that every year worldwide about a million patients might be exposed to doses of the order of 100 mGy of low-LET radiation, due to recurrent application of radioimaging procedures. This paper presents a synthesis of recent epidemiological evidence on radiation-related cancer risks from low-LET radiation doses of this magnitude. Evidence from pooled analyses and meta-analyses also involving epidemiological studies that, individually, do not find statistically significant radiation-related cancer risks is reviewed, and evidence from additional and more recent epidemiological studies of radiation exposures indicating excess cancer risks is also summarized. Cohorts discussed in the present paper include Japanese atomic bomb survivors, nuclear workers, patients exposed for medical purposes, and populations exposed environmentally to natural background radiation or radioactive contamination. Taken together, the overall evidence summarized here is based on studies including several million individuals, many of them followed-up for more than half a century. In summary, substantial evidence was found from epidemiological studies of exposed groups of humans that ionizing radiation causes cancer at acute and protracted doses above 100 mGy, and growing evidence for doses below 100 mGy. The significant radiation-related solid cancer risks observed at doses of several 100 mGy of protracted exposures (observed, for example, among nuclear workers) demonstrate that doses accumulated over many years at low dose rates do cause stochastic health effects. On this basis, it can be concluded that doses of the order of 100 mGy from recurrent application of medical imaging procedures involving ionizing radiation are of concern, from the viewpoint of radiological protection.

대학 실험실에서의 유기화합물 노출에 의한 건강위험성 평가에 관한 연구

Objectives: Laboratories have various latent physical, chemical, biological, and ergonomical factors according to the diversification and fusion of research and development activities. This study aims to investigate the chemical exposure concentrations of college laboratories and evaluate their health risks, and use them as basic data to promote the health of college students. Methods: The sampling and analysis of harmful chemicals in the air in laboratories were performed using Method 1500 of the U.S. National Institute for Occupational Safety and Health (NIOSH)의 Method 1500. The harmful chemicals in the laboratories were divided into carcinogenic and non-carcinogenic chemicals. Risk assessment was performed using the cancer risk (CR) for carcinogenic chemicals and using the hazard index (HI) for non-carcinogenic chemicals. Results: The harmful chemicals in college laboratories consisted of acetone, diethyl ether, methylene chloride, n-hexane, ethyl acetate, chloroform, tetrahydrofuran, toluene, and xylenes. They showed the highest concentrations in laboratories A (acetone 0.001~2.34ppm), B (chloroform 0.95~6.35ppm), C (diethyl ether 0.08~8.68ppm), and D (acetone 0.07~14.96ppm). The risk assessment result for non-carcinogenic chemicals showed that the HI of methylene chloride was 2.052 for men and 2.333 for women, the HI of N-hexane was 4.442 for men and 5.05 for women. Thus, the HI values were higher than 1. The risk of carcinogenic chemicals is determined by an excess cancer risk (ECR) value of 1.0x10-5, which means that one in 100,000 people has a cancer risk. The ECRs of chloroform exceeded 1.0x10-5 for both men and women, indicating the possibility of cancer risk. Conclusion: College laboratories showed the possibility of non-carcinogenic health risks for methylene chloride, n-hexane, tetrahydrofuran (THF), toluene, and xylenes, and carcinogenic health risks for chloroform, methylene chloride. However, this study used the maximum values of measurements to determine the worst case, and assumed that the subjects were exposed to the corresponding concentrations continuously for 8 hours per day for 300 days per year. In consideration of the nature of laboratory environment in which people are intermittently exposed, rather than continuously, to the chemicals, the results of this study has an element of overestimation.

Bioaccumulation and Consumption Safety of a Sea Food, Gastropod Mollusc (Thais coronata): Polycyclic Aromatic Hydrocarbon (PAH) Perspective

&#x0D; &#x0D; &#x0D; Seafood and other environmental matrices are major entry route of harmful pollutants into humans due to constant contamination of the aquatic environment hence requires monitoring. This study scientifically explored the hypothesis that benthic gastropods bioaccumulate harmful pollutants that pose health risk to consumers of the sea food. Fifty samples of Thais coronata were collected per site from major regional fish landings. Two hundred samples were collected monthly for eight months to determine the concentrations of polycyclic aromatic hydrocarbon-PAH and possible health risks due to consumption using regulatory limits for guidance. Total PAH concentrations (μg/kg) varied between 65.68–173.52 suggesting differences in consumed concentrations at different times. The concentration of individual PAH congeners (1.376 ± 0.07-40.356±2.21 μg/kg) and PAH4 were below the European Union maximum limits. The Daily Dietary Intake values ranged from 0.075-2.212 μg/kg for individual PAH congeners while that of PAH4 was 1.359 μg/kg and were all below their respective reference oral doses. The carcinogenic potencies of the PAH congeners ranged from 0.001-143.389, the carcinogenic toxic equivalents (TEQs) of all PAH congeners was 0.1522 while that of PAH4 was 0.0044. The Excess cancer risk (ECR) value (10-8–10-5) was within USEPA guideline of 10-6 while the margin of exposure (MOE) of individual PAHs and PAH4 were higher than critical border line of 10,000 given by European Food Safety Authority but diagnostic ratio suggested PAH sources of pyrogenic origin in samples monitored. The study concluded low health risk for consumers of the shellfish (Thais coronata) in the study region but with recommendation advisory for regular monitoring to observe changes.&#x0D; &#x0D; &#x0D;

Occupational exposures to particulate matter and PM2.5-associated polycyclic aromatic hydrocarbons at the Agbogbloshie waste recycling site in Ghana

Electronic waste (e-waste) disposal and recycling activities such as burning and smelting can emit particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), and other pollutants that expose workers and nearby communities. At informal e-waste recycling facilities, both emission controls and protective measures for workers are absent. This study characterizes personal exposures (breathing zone) of PM and PAHs of e-waste workers at the large Agbogbloshie e-waste site in Accra, Ghana. We collected gravimetric and optical measurements of PM2.5 and PM10 using shift samples for workers and for an age- and gender-matched reference population. PM2.5 filters were analyzed for 26 PAHs using gas chromatography/mass spectroscopy. Among e-waste workers, PM2.5 and PM10 concentrations were 99 ± 56 and 218 ± 158 µg/m3 (median ± interquartile range, optical measurements), respectively; these levels were 78 and 57% higher, respectively, than levels measured at a fixed site that was centrally located at the waste site. In the reference community, breathing zone PM2.5 and PM10 levels were lower, 49 ± 20 and 131 ± 108 µg/m3, respectively, and the fraction of coarse PM was larger. We detected all 26 target PAHs, of which naphthalene and phenanthrene were the most abundant. PAH concentrations were weakly correlated to PM levels, but PAH abundances, representing the fraction of PAH mass to the total PM2.5 mass collected, were strongly and inversely correlated to PM levels, suggesting multiple and different sources of PAHs and PM that affected exposures. Both PM and PAH levels were elevated for workers performing burning and dismantling, and both exceeded standards or risk-based guidelines, e.g., lifetime excess cancer risks for several PAHs were in the 10−4 to 10−6 range, indicating the need to reduce emissions as well as provide respiratory protection. The study emphasizes the importance of using personal and shift samples to accurately characterize worker exposure.

Long-term environmental surveillance of PM2.5-bound polycyclic aromatic hydrocarbons in Jinan, China (2014–2020): Health risk assessment

We established long-term surveillance sites in Jinan city to monitor PM2.5 particles (PM2.5) and PM2.5-bound PAHs (2014–2020). The range of PM2.5 was 15–230 µg/m3. The average annual ƩPAH16 were 433 ± 271 ng/m3 (industrial area) and 299 ± 171.8 ng/m3 (downtown). PAHs captured in winter accounted for 61.5% (industrial area) and 59.1% (downtown) of total PAHs. A hazardous seasonal benzo[a]pyrene level was detected in 2015–2016 winter as 14.03 ng/m3 (14 folds of EU standard). The dominant PM2.5-bound PAHs were benzo[b]fluoranthene (24–26%), chrysene (19–20%), benzo[g,h,i]perylene (15%), Indeno(1,2,3-cd)pyrene (12%) and Benzo[a]pyrene (10%). Toxic equivalent quotients of PAHs were 4.93 ng/m3 (industrial area) and 3.13 ng/m3 (downtown). Excess cancer risks (ECRs) were 4.3 × 10−4 ng/m3 and 2.7 × 10−4 ng/m3, respectively. The ECRs exceeded EPA regulatory limit of 1 × 10−6 ng/m3 largely. Non-negligible excess lifetime cancer risks were found as 36 and 26 related cancer incidences per 1,000,000 people. Consistently, local prevalence of lung cancer raise from 56.97/100,000 to 72.38/100,000; the prevalence of thyroid cancer raise from 10.12/100,000 to 45.26/100,000 from 2014 to 2020. Our findings suggest an urgent need to investigate the adverse health effects of PAHs on local population and we call for more strictly restriction on coal consumption and traffic tail gas emission.

Overview of epidemiological studies of nuclear workers: opportunities, expectations, and limitations ∗ ∗ Based upon an invited presentation in Special Session 9 of the IRPA15 Virtual Congress, January–February 2021.

Epidemiological studies of those exposed occupationally to ionising radiation offer an important opportunity to directly check the assumptions underlying the international system of radiological protection against low-level radiation exposures. Recent nuclear worker studies, notably the International Nuclear Workers Study (INWORKS) and studies of the Mayak workforce in Russia, provide powerful investigations of a wide range of cumulative photon doses received at a low dose-rate over protracted periods, and broadly confirm radiation-related excess risks of leukaemia and solid cancers at around the levels predicted by standard risk models derived mainly from the experience of the Japanese atomic-bomb survivors acutely exposed principally to gamma radiation. However, the slope of the dose-response for solid cancers expressed in terms of the excess relative risk per unit dose, ERR/Gy, differs between INWORKS and Mayak, such that when compared with the slope derived from the atomic-bomb survivors, INWORKS does not provide obvious support for the use in radiological protection of a dose and dose-rate effectiveness factor greater than one whereas the Mayak workforce apparently does. This difference could be a chance effect, but it could also point to potential problems with these worker studies. Of particular concern is the adequacy of recorded doses received in the early years of operations at older nuclear installations, such as the potential for ‘missed’ photon doses. A further issue is how baseline cancer rates may influence radiation-related excess risks. There is scope for a considerable increase in the statistical power of worker studies, with longer follow-up capturing more deaths and incident cases of cancer, and further workforces being included in collaborative studies, but the difficulties posed by dosimetry questions should not be ignored and need to be the subject of detailed scrutiny.

The perspectives of survivors of Hodgkin lymphoma on lung cancer screening: A qualitative study.

Hodgkin lymphoma survivors (HLS) are at excess risk of lung cancer as a consequence of HL treatment. HLS without a heavy smoking history are currently unable to access lung cancer screening (LCS) programmes aimed at ever smokers, and there is an unmet need to develop a targeted LCS programme. In this study we prospectively explored HLS perspectives on a future LCS programme, including motivating factors and potential barriers to participation, with the aim of identifying ways to optimise uptake in a future programme. Semistructured telephone interviews were conducted with HLS, aged 18-80 and lymphoma-free for ≥5 years, selected from a clinical database (ADAPT). Participants provided informed consent. Data were analysed using inductive thematic analysis. Despite awareness of other late effects, most participants were unaware of their excess risk of lung cancer. Most were willing to participate in a future LCS programme, citing the potential curability of early-stage lung cancer and reassurance as motivating factors, whilst prior experience of healthcare was a facilitator. Whilst the screening test (a low dose CT scan) was considered acceptable, radiation risk was a concern for some and travel and time off work were potential barriers to participation. Our results suggest that most HLS would participate in a future LCS programme, motivated by perceived benefits. Their feedback identified a need to develop educational materials addressing lung cancer risk and concerns about screening, including radiation risk. Such materials could be provided upon an invitation to LCS. Uptake in a future programme may be further optimized by offering flexible screening appointments close to home.

Second Primary Malignancies Among Patients with Multiple Myeloma

Introduction. Treatment for multiple myeloma (MM) has undergone significant transformation in the past decade with the introduction of novel therapeutic agents, including proteasome inhibitors (PI), immunomodulatory imides (IMiD) and monoclonal antibodies (mAb), leading to significant improvements in drug tolerability, treatment response and overall survival. As overall survival improves, patients with MM are at increased risk of developing second primary malignancies. Therefore, we evaluated the incidence of second primary malignancies among patients with MM.Methods. Using data from 30,630 1-year survivors of MM reported to 13 cancer registries that constitute the Surveillance, Epidemiology, and End Results (SEER) program (1992-2015; median survival time, 4.5 years), we calculated standardized incidence ratios (SIR) for all second primary malignancies, any solid and any hematologic malignancy and cancer sites among patients with MM, stratified by calendar year of first primary diagnosis consistent with advances in treatment for MM (1992-1999, 2000-2007, 2008-2015). Individual treatment data were unavailable. Excess absolute risk (excess cancer risk per 10,000 person-years) was calculated as ([observed cancers minus expected cancers]/person-years) multiplied by 10,000. Hazard ratios were calculated using Cox proportional hazards adjusted for confounders. Analyses were conducted using SAS v.9.4.Results. Overall, among 30,630 1-year survivors of first primary MM, the standardized incidence of any second primary malignancy was significantly increased (n=1,962; SIR=1.15, 95% confidence interval [CI], 1.10-1.20; P<0.0001) and SIRs were elevated in each of the three calendar periods (1992-1999, SIR=1.14; 2000-2007, SIR=1.11; 2008-2015, SIR=1.22). Of all the second primary malignancies, the incidence of any solid tumor was increased (n=1,584; SIR=1.05, 95% CI 0.99-1.10; P=0.09), albeit not significantly, with SIRs for specific solid tumor sites ranging from 0.80 to 2.23. In contrast, the incidence of any hematologic malignancy overall was significantly increased (n=317; SIR=2.28, 95% CI 2.03-2.54; P<0.0001) with the largest SIRs observed for any leukemia (SIR=5.86, 95% CI 4.91-6.94; P=<0.0001) and SIRs for leukemia subtypes ranging from 2.07 to 14.87. The SIR for any lymphoma was also increased but to a lesser extent (SIR=1.57, 95% CI 1.35-1.82; P<0.0001). Notably, SIRs for any leukemia decreased over the three time periods (1992-1999, SIR=6.40; 2000-2007, SIR=5.77; 2008-2015, SIR=5.51) whereas SIRs for any lymphoma increased (1992-1999, SIR=1.21; 2000-2007, SIR=1.60; 2008-2015, SIR=1.81) leading to an excess absolute risk of any hematologic malignancy of 1.5 per 10,000 person-years in the latest calendar period. No differences were observed by sex or ancestry.Discussion. We confirm that MM patients are at increased risk of second primary malignancies, and particularly other blood cancers. The transposition of leukemia and lymphoma incidence over time may reflect the effect of treatment changes in recent years. Additional studies, which include individual treatment data and longer follow up time from large and diverse populations, are required to further define these relationships. DisclosuresNo relevant conflicts of interest to declare.

Tolerability of Breast Radiotherapy Among Carriers of ATM Germline Variants.

Of 167 patients with ATM germline variants presenting to our institution with breast cancer, 91 received RT. Treatment-related toxicity was ascertained from medical records and graded across organ systems. Toxicities grade > 2 were recorded from the end of treatment to last evaluable follow-up and were analyzed according to ATM variant pathogenicity. Of 91 evaluable carriers of ATM variants, with a median follow-up of 32 months following RT, 25% (n = 23) harbored a PV, whereas 75% (n = 68) harbored a variant of uncertain significance (VUS). Prevalence of grade ≥ 2 toxicity unrelated to post-mastectomy reconstruction among patients with ATM PV was: 32% at the end of treatment (v 34% for VUS carriers), 11% at 1 year of follow-up (v 4% for VUS carriers), and 8% at the last follow-up (v 13% for VUS carriers), consistent with previous studies of RT among unselected populations. No grade 4 or 5 toxicities were observed. ATM variant pathogenicity was not associated with local toxicity, contralateral breast cancer, or secondary malignancy in this limited cohort of patients who received breast RT. We found no evidence of excess RT-associated toxicity among carriers of pathogenic ATM germline variants. Breast-conserving therapy and adjuvant RT may be safely considered among appropriately selected carriers of ATM germline variants.

Acute urinary retention and risk of cancer: population based Danish cohort study

ObjectiveTo examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention.DesignNationwide population based cohort study.SettingAll hospitals in Denmark.Participants75 983 patients aged 50 years...

Cancer incidence and mortality according to pre-existing heart failure in a community-based cohort

Abstract Background Studies assessing whether heart failure (HF) is associated with an excess risk of cancer and cancer-related mortality yielded conflicting results. Here, we assessed the incidence and mortality of cancer according to the presence of HF in a community-based cohort. Methods By reviewing the health care records of the Puglia region in Italy, we first selected individuals ≥50-year-old, with no history of cancer within 3 years before the baseline evaluation and ≥5 years of follow-up, during the period from January 1st, 2005 to December 31st, 2013. Next, we matched 1:1 104,020 subjects with HF at baseline and 104,020 controls based on age, sex, Charlson Comorbidity Index, Drug-Derived Complexity Index, and follow-up duration. Cancer incidence and mortality were analyzed by Kaplan-Meier method and Cox regression models. Fine and Grey's regression model was also used to compare cancer-specific mortality while taking into account the competing risk of non-cancer death. Results Overall, the mean age of the study population was 76±10 years and the mean follow-up was 5.7 years. The incidence rate of cancer in HF patients and controls was 21.36 (95% CI, 20.98–21.74) and 12.42 (95% CI, 12.14–12.72) per 1000 person/years, respectively, corresponding to a 76% higher risk of incident cancer in HF patients (HR, 1.76; 95% CI, 1.71–1.81). HF patients also died from cancer more frequently than controls (HR 4.11; 95% CI, 3.86–4.38; Figure 1). This excess mortality was highest when age was &amp;lt;70 years (HR 7.54, 95% CI 6.33–8.98), and declined in subjects aged 70–79 years (HR 3.80, 95% CI 3.44–4.19) and ≥80 years (HR 3.10, 95% CI 2.81–3.43). The association of HF with cancer mortality was confirmed in the competing risk analysis (HR 3.48, 95% CI 3.27–3.72), as well as the interaction with age: &amp;lt;70 years of age: HR 6.65, 95% CI 5.60–7.94; 70–80 years: HR 3.14, 95% CI 2.84–3.48; and ≥80 years: HR 2.81, 95% CI 2.55–3.10. The HF-related risk applied to the majority of cancer types, with the exception of neoplasm of the male reproductive system. Interestingly, among HF patients a high consumption of loop diuretic (&amp;gt;37.5 mg/d of furosemide) was associated with a higher mortality for cancer (HR 1.34, 95% CI 1.26–1.42 vs. ≤37.5 mg/d). Conclusions The analysis of this large community-based sample suggests that HF does portend an increased risk of cancer and cancer-related mortality, which is blunted, yet remains substantial, with increasing age and competing risk of dying from other causes. The risk of cancer may be heightened when HF is poorly compensated. Funding Acknowledgement Type of funding sources: None. Figure 1. Cancer mortality in HF patient

Ranitidine Use and Risk of Upper Gastrointestinal Cancers

Abstract Background: The discovery that ranitidine is contaminated with N-nitrosodimethylamine, a suspected human carcinogen, raises the hypothesis of a gastrointestinal carcinogenic effect; however, evidence remains inconclusive. Methods: We used the nationwide Danish Prescription Registry to identify a cohort of incident ranitidine users and two active comparator cohorts comprising users of other histamine-2 receptor blockers (H2RB) and users of proton pump inhibitors (PPI). All Danish adults with a first prescription of ranitidine, other H2RBs, or PPIs in 1996 through 2008 were followed virtually completely through 2018 for incidence of esophageal, stomach, liver, and pancreatic cancers. We used Cox regression with propensity-score weighting to calculate hazard ratios and 10-year cumulative risk with 95% confidence intervals. Results: We ascertained 276 newly diagnosed esophageal, 342 stomach, 133 hepatocellular, and 517 pancreatic cancers among ranitidine users during follow-up (median 14 years). In comparison with use of other H2RBs or PPIs, we found no consistent evidence of increased HRs or excess 10-year cumulative risk of any upper gastrointestinal cancer following ranitidine use. We observed no association after restriction to subjects with at least 5 or 10 prescriptions or those with 10 prescriptions and at least 10 years of follow-up. Conclusions: Our large prospective study using high-quality prescription and cancer incidence data, with two active comparator groups, provides no compelling evidence that ranitidine increases the risk of upper gastrointestinal cancers. Impact: Our results, which do not support any carcinogenic effect on esophagus, stomach, liver or pancreas, should be reassuring for millions of concerned past users of ranitidine.

Excess Body Weight and Long-Term Incidence of Lung and Colon Cancer in Men; Follow-Up Study of 43 Years.

Most evidence for an association between excess body weight and cancer risk has been derived from studies of relatively short duration with little reference to the effect on tumor site. This study was designed to evaluate the association between categories of body mass index (BMI: <20, 20–25, 25–30, and >30 kg/m2) and the incidence of colon and lung cancer over 43 years of follow-up (1963–2006), in 10,043 men from the Israeli Ischemic Heart Disease (IIHD) prospective cohort (mean age at baseline 49.3 years, mean BMI 25.7 kg/m2). Data from the Israel National Cancer Registry was linked with the IIHD, and the Cox proportional hazards regression model was applied to analyze the relative risks for lung and colon cancer across BMI categories at baseline. Three hundred cases of lung cancer (2.9%) and 328 cases of colon cancer (3.3%) were diagnosed in the total population. Applying a multivariate model adjusted for age, smoking intensity, and total cholesterol, higher BMI category was associated with an increased risk of colon cancer [HR = 1.22 (95% CI 1.02–1.45)], and with a decreased risk for lung cancer [HR = 0.66 (95% CI 0.56–0.77)]. In this long-term follow-up study over four decades, we observed a consistent dose-response pattern between BMI and increased risk for colon cancer, but decreased risk for lung cancer. Specific associations between excess body weight and cancer risk may suggest different patterns of body fat and cancer incidence at a given site.

Evaluation of Health Risk from Concentrations of Heavy Metal in PM-10 and PM-2.5 particles at Sasang Industrial Complex of Busan, Korea

We investigated the distribution of hazardous heavy metals (As, Cr6+, Ni, Cd, Pb, and Mn) and estimated the health risk related to the heavy metals in fine dust (PM-10 and PM-2.5) of Sasang industrial complex, Busan, Korea. The concentration of fine dust in the industrial complex was 1.2 times higher than in a residential area, while harmful heavy metals showed a difference of at least 1.3 times (Cd) and up to 6.5 times (Ni). The concentration of fine dust and carcinogenic heavy metals in the industrial complex increased significantly compared to the residential area in spring (March to May) and winter (December to February) months. A risk assessment was performed using Monte-Carlo simulations containing a four-step procedure. During hazard identification, As, Cr6+ Ni, Cd, and Pb were categorized as human carcinogens and probable human carcinogens and evaluated for their levels of excess cancer risk. For concentrations of over 90% Cr6+ and As, the excess cancer risk was over 10-5 (1 person per 100,000). The non-cancer hazard index of As, Cr6+, Cd, and Mn was below the limit value of 1.

The possible impact of passive smoke exposure on radiation-related risk estimates for lung cancer among women: the life span study of atomic bomb survivors

Purpose Analyses of the Life Span Study cohort of atomic bomb survivors have shown a statistically significant sex difference in the excess risk of incident lung cancer due to radiation exposure, with the radiation-related excess relative risk per gray (ERR/Gy) for women approximately 4 times that for men, after accounting for active smoking. We sought to determine the extent to which this risk difference could be explained by adjustment for passive smoke exposure, which is a known risk factor for lung cancer that was not measured among Life Span Study participants, and which could be particularly influential among female never-smokers. Materials and methods The Life Span Study includes survivors of the atomic bombings of Hiroshima and Nagasaki and city residents who were not in either city at the time of the bombings, matched to survivors on city, sex, and age. First primary lung cancers were identified from population-based cancer registries between 1958 and 2009. Data on active smoking were obtained from mailed surveys and in-person questionnaires (1965–1991). We calculated passive smoke exposure for female never-smokers by attributing smoking pack-years at various intensities (5–50%) based on smoking patterns among men, stratified by city, birth year, radiation dose, and lung cancer status. Poisson regression models with additive and multiplicative interactions between radiation dose and smoking were used to estimate sex-specific radiation-related excess relative risks for lung cancer. Results During the study period, 2,446 first primary lung cancers were identified among 105,444 study participants. On average, male smokers started smoking 19.5 cigarettes per day at 21.5 years old. Partially attributing male smoking patterns to female never-smokers—to approximate passive smoke exposure—yielded lower radiation-related ERR/Gy estimates for women under a multiplicative radiation-smoking interaction model, leading to a lower female-to-male ratio of ERR/Gy estimates; however, this difference was evident only at very high passive smoke intensities. Under an additive radiation-smoking interaction model, the results were unchanged. Conclusions Our results are consistent with the possibility that failure to account for passive smoke might contribute, in small part, to the higher radiation risk estimates for lung cancer among women compared to men in the Life Span Study.

The Hiroshima A-Bomb Black Rain and the Lifespan Study; A Resolution of the Enigma

The Japanese Lifespan Study (LSS) of the A-Bomb survivors is the principal basis of the current legal radiological framework. Evidence provided for the first time here shows that internal exposure to radiologically significant quantities of Uranium-234 contained in sub-micron particle rainout from the un-fissioned weapon warhead, the Black Rain, is a missing exposure in the LSS analysis. It is argued that this is responsible for a background excess cancer risk in all the LSS dose groups. This, together with epidemiological evidence based on unexposed controls falsifies the LSS cancer vs. dose regression coefficients for internal exposure.