The First Attempt to Reevaluate Radon and Thoron Exposure in Gansu Province Study Using Radon-Thoron Discriminating Measurement Technique.

Although the epidemiological studies provide evidence for an increased risk of lung cancer risk associated with residential radon, an issue of radon-thoron discrimination remains to be solved. In this study, an updated evaluation of lung cancer risk among the residents in Gansu, China was performed where one of the major epidemiological studies on indoor radon demonstrated an increased risk of lung cancer. We analyzed data from a hospital-based case-control study that included 30 lung cancer cases and 39 controls with special attention to internal exposure assessment based on the discriminative measurement technique of radon isotopes. Results from the analyses showed non-significant increased lung cancer risks; odds ratios (ORs) adjusted for age, smoking, and total income were 0.35 (95% CI: 0.07-1.74) and 0.27 (95% CI: 0.04-1.74) for groups living in residences with indoor radon concentrations of 50-100 Bq m-3 and over 100 Bq m-3, respectively, compared with those with < 50 Bq m-3 indoor radon concentrations. Although the small sample size hampers the usefulness of present analyses, our study suggests that reevaluation of lung cancer risk associated with residential radon in the epidemiological studies will be required on the basis of precise exposure assessment.

Esophageal cancer in relation to alcohol drinking and tobacco use among men in Kerala, India - Karunagappally cohort.

BACKGROUND: In the Karunagappally cohort, esophageal cancer is the third most common cancer with an age-adjusted incidence rate of 6.2 per 100,000 person-years among men. The present study analyzed the risk of esophageal cancer in relation to alcohol drinking and tobacco use. METHODS: The study included 65,528 men aged 30-84 years in the Karunagappally cohort, India. RESULTS: Poisson regression analysis showed that alcohol drinking significantly increased (P = 0.027) the risk of esophageal cancer and the relative risk (RR) for current drinkers was 1.6, (95 % confidence interval (CI) = 1.1-2.3). The risk increased significantly in heavy alcohol drinkers (250 g of ethanol or above per day) (RR = 2.1, 95 % CI = 1.2-3.5) (P for trend = 0.014) and among current arrack consumers (RR = 1.8, 95 % CI = 0.99-3.29) (P for trend = 0.025). Current bidi and cigarette smokers showed an increase in the trend of cancer risk. A significantly higher risk was seen in those who had started smoking bidi before the age of 18 years, RR = 1.9 (95 % CI = 1.1-3.3) (P for trend = 0.044). Furthermore, increased RR for heavy bidi and cigarette smokers were 1.6 (95 % CI = 1.1-2.5) and 2.4 (95 % CI = 1.3-4.5), respectively. CONCLUSION: To the best of our knowledge, this is the first cohort study in India to report an increased esophageal cancer risk with respect to alcohol drinking.

Lens opacity prevalence among the residents in high natural background radiation area in Yangjiang, China.

The aim of the study was to evaluate the risk and threshold doses of lens opacity among residents exposed to low-dose radiation. Residents aged ≥45 years were recruited from a high natural background radiation (HNBR) area in Yangjiang City and a control area selected from nearby Enping City. Lens opacities (LOPs) were classified according to the Lens Opacities Classification System (LOCS) III system. Face-to-face interviews were conducted to collect information on lifestyles, migration and medical history. Life-time cumulative doses were estimated using gender, age, occupancy factors and environmental radiation doses received indoors and outdoors. Logistic regression analyses were conducted to estimate the dose response and determine thresholds. In the HNBR area, among 479 study participants, 101 (21.1%), 245(51.1%) and 23 cases (4.8%), respectively, of cortical, nuclear and posterior subcapsular (PSC) LOPs were found. In the control area, those types of LOPs were identified among 58 cases (12.6%), 206 cases (51.2%) and 6 cases (1.3%) of 462 examinees, respectively. Cumulative eye lens dose was estimated to be 189.5 ± 36.5 mGy in the HNBR area. Logistic analyses gave odds ratios at 100 mGy of 1.26 [95% confidence interval (CI) 1.00-1.60], 0.81 (95% CI 0.64-1.01) and 1.73 (95% CI 1.05-2.85) for cortical, nuclear and PSC LOPs, respectively. For cortical LOPs, a logistic analysis with a threshold dose gave a threshold estimate of 140 mGy (90% CI 110-160 mGy). The results indicated that population exposed to life-time, low-dose-rate environmental radiation was at an elevated risk of cortical and PSC LOPs. A statistically significant threshold dose was obtained for cortical LOPs and no threshold dose for PSC LOPs.

Japanese Legacy Cohorts: Six-Prefecture Cohort Study (Hirayama Cohort Study).

Late Dr Takeshi Hirayama and his colleagues conducted a mortality follow-up of a large-scale cohort in six prefectures in Japan. This study is called the six-prefecture cohort study or Hirayama Cohort Study. The study subjects were residents aged 40 years or older at the baseline survey in 1965, which covered 94.8% of residents identified in the study area by the National Census conducted on October 1, 1965. The mortality of 264,118 cohort members was followed until the end of 1982. One of the most important findings made by this study was an association between second-hand smoke exposure and lung cancer. This finding is the origin of the worldwide spread of smoking ban in indoor public venues and workplaces. Other major findings obtained from the study are also briefly described in this article.

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India.

PURPOSE: Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. METHODS: The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. RESULTS: We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. CONCLUSIONS: The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Suppression of methylmercury-induced MIP-2 expression by N-acetyl-L-cysteine in murine RAW264.7 macrophage cell line.

BACKGROUND: The aim of this study is to examine the inflammatory-cytokine expressions in the presence of non-cytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inflammatory protein-2 (MIP-2), keratinocyte chemoattractant (KC), and monocyte chemoattractant protein-5 (MCP-5). MIP-2 and KC are murine functional homologues of human IL-8 and MCP-5 for human MCP-1. Furthermore, we examined the suppressive effect of N-acetyl-L-cysteine (NAC) on the MeHg-induced inflammatory cytokines. METHODS: In a murine RAW264.7 macrophage cell line, MeHg-induced cytokine expressions were measured using real-time PCR. The suppressive effect of NAC was examined by putting it into the culture medium together with MeHg (co-treatment). In addition, pre- and post-treatment experiments were conducted, in which the cells were treated with NAC before and after MeHg exposure, respectively. RESULTS: Exposure to a non-cytotoxic dose of MeHg up-regulated the mRNA expression of MIP-2 and MCP-5. On the other hand, KC expression was not induced in the presence of MeHg. Effect of MeHg on MIP-2 expressions was suppressed by pre-, co-, and post-treatment with NAC. However, the suppressive effect of pre-treatment was less than the post-treatment, which was as effective as co-treatment. CONCLUSION: In functional homologues of human IL-8, only MIP-2 expression, not KC, was activated in the presence of non-cytotoxic dose of MeHg in murine RAW264.7 macrophage cell line. The more evident inhibitory effect of NAC observed in post-treatment experiments suggests a possible involvement of intracellular activities such as antioxidant effects.

The association between high birth weight and the risks of childhood CNS tumors and leukemia: an analysis of a US case-control study in an epidemiological database.

BACKGROUND: High birth weight (BW), 4000 g or larger, is an established risk factor for childhood leukemia. However, its association with central nervous system (CNS) tumor risk is yet unclear. The present study examined it, analyzing data obtained from a case-control study conducted among three states from the US. The association with childhood leukemia risk was also further examined. METHODS: In this study, a data set provided by the Comprehensive Epidemiologic Data Resource was analyzed with an official permission. The original case-control study was conducted to examine the association between paternal preconception exposure to ionizing radiation and childhood cancer risk. Cases with childhood cancer were mainly ascertained from local hospitals, and controls were selected, matched with birth year (1-year category), county of residence, sex, ethnicity and maternal age (+/-2 years). Since the ID numbers were unavailable, conventional logistic analyses were conducted adjusting for those matching variables except for the county of residence. In addition to those variables, gestational age, age at diagnosis and study sites as covariables were included in the logistic models. RESULTS: Analyzed subjects were 72 CNS tumor cases, 124 leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of CNS tumor risk for children with low BWs (<2500 g) and high BWs (>4000 g) were 2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)], respectively. When high-BW children were restricted to those who were large for gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7; 95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6), respectively. In the normal range of BW (2500-4000 g), higher BW was positively associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the association with leukemia risk was not significant (beta = -0.0002, p for trend = 0.475). CONCLUSION: High-BW and LGA children had an elevated childhood CNS tumor risk. In the normal BW range, the BW itself was positively related to CNS tumor risk. No significant association between BW and childhood leukemia risk was observed in this study.

Hair mercury levels in relation to fish consumption among Vietnamese in Hanoi.

People are exposed to methylmercury (MeHg) mainly through fish consumption, which is increasing in Vietnam. However, little information is available on estimating the health risk of MeHg exposure through fish consumption in Vietnam. The present study examined the association between mercury (Hg) levels in hair and selenium (Se) levels in toenails of 196 Vietnamese people and their fish consumption, using a dietary questionnaire to obtain information pertinent for assessing health risk owing to MeHg exposure. The geometric mean of Hg levels in the hair of males and females was 617 ng/g and 575 ng/g, respectively. We found that Hg levels in the hair of 98% of the Vietnamese study subjects were lower than the provisional tolerable weekly intake for MeHg (1.6 µg Hg/kg body weight; which is equivalent to a hair Hg concentration of approximately 2,300 ng/g, with an uncertainty factor of 6.4). There were significant differences in the age-adjusted geometric mean of Hg levels found in hair from females related to their frequency of freshwater fish consumption. The levels of Hg in hair and Se in toenails increased with an increased frequency of marine fish consumption, and both showed a significant positive correlation in subjects who consumed marine fish ≥ once/week. This is the first cross-sectional study to investigate the association between hair Hg levels and fish consumption in Vietnam. These findings provide valuable information for future assessments of the health risk of MeHg exposure through fish consumption in Vietnam.

Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

COMPARISON OF THE PERIPHERAL DOSES FROM DIFFERENT IMRT TECHNIQUES FOR PEDIATRIC HEAD AND NECK RADIATION THERAPY.

Intensity-modulated radiation therapy (IMRT) can deliver high and homogeneous doses to the target area while limiting doses to organs at risk. We used a pediatric phantom to simulate the treatment of a head and neck tumor in a child. The peripheral doses were examined for three different IMRT techniques [dynamic multileaf collimator (DMLC), segmental multileaf collimator (SMLC) and volumetric modulated arc therapy (VMAT)]. Peripheral doses were evaluated taking thyroid, breast, ovary and testis as the points of interest. Doses were determined using a radio-photoluminescence glass dosemeter, and the COMPASS system was used for three-dimensional dose evaluation. VMAT achieved the lowest peripheral doses because it had the highest monitor unit efficiency. However, doses in the vicinity of the irradiated field, i.e. the thyroid, could be relatively high, depending on the VMAT collimator angle. DMLC and SMLC had a large area of relatively high peripheral doses in the breast region.

Radiation dose due to radon and thoron progeny inhalation in high-level natural radiation areas of Kerala, India.

In order to evaluate internal exposure to radon and thoron, concentrations for radon, thoron, and thoron progeny were measured for 259 dwellings located in high background radiation areas (HBRAs, outdoor external dose: 3-5 mGy y-1) and low background radiation areas (control areas, outdoor external dose: 1 mGy y-1) in Karunagappally Taluk, Kerala, India. The measurements were conducted using passive-type radon-thoron detectors and thoron progeny detectors over two six-month measurement periods from June 2010 to June 2011. The results showed no major differences in radon and thoron progeny concentrations between the HBRAs and the control areas. The geometric mean of the annual effective dose due to radon and thoron was calculated as 0.10 and 0.44 mSv, respectively. The doses were small, but not negligible compared with the external dose in the two areas.

Waterpipe Tobacco Smoking and Gastric Cancer Risk among Vietnamese Men.

BACKGROUND: The association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested. METHODS: A hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003-2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models. RESULTS: The group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4-0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3-2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2-6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2-11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk. CONCLUSION: The present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men.

Cytotoxic effects of NF­κB inhibitors in combination with anti­herpes agents on Epstein­Barr virus­positive gastric carcinoma in vitro.

Epstein-Barr virus (EBV) infection in tumor cells is usually restricted to the latent form, indicating that the induction of viral lytic infection may present a novel approach for the treatment of EBV­associated tumors. By contrast, EBV lytic replication is inhibited by high­levels of nuclear factor (NF)­κB, which suggests that NF­κB inhibitors may activate lytic replication from the latent form. In the current study, the addition of NF­κB inhibitors (Bay11­7082, Z­LLF­CHO and aspirin) was observed to induce the EBV lytic genes BZLF1, BRLF1 and BMRF1 in EBV­positive gastric cancer (GC) cells. Both EBV­positive and ­negative GC cells were treated with different concentrations of anti­herpes agents and the cytotoxic effects were measured at different time points following induction of EBV lytic replication. A marginal dose­ and time­dependent reduction in cell viability was observed for EBV­positive and­negative GC cells. The cytotoxic effects of NF­κB inhibitors on EBV­positive GC cells were enhanced by the addition of the anti­herpes agents, ganciclovir, acyclovir, foscarnet and brivudine (P<0.05). However, there was no significant synergistic effect on EBV­negative GC cells. The combination of 5 mM aspirin and ganciclovir exhibited the highest cytotoxic effect in EBV­positive GC cells (CC50=7.2 µg/ml).

Gastric cancer risk in relation to tobacco use and alcohol drinking in Kerala, India--Karunagappally cohort study.

AIM: To assess the risk of gastric cancer (GC) in relation to tobacco use and alcohol drinking in the Karunagappally cohort in Kerala, South India. METHODS: This study examined the association of tobacco use and alcohol drinking with GC incidence among 65553 men aged 30-84 in the Karunagappally cohort. During the period from 1990-2009, 116 GC cases in the cohort were identified as incident cancers. These cases were identified from the population-based cancer registry. Information regarding risk factors such as socioeconomic factors and tobacco and alcohol habits of cohort members were collected from the database of the baseline survey conducted during 1990-1997. The relative risks (RRs) and the corresponding 95% confidence intervals (95%CIs) for tobacco use were obtained from Poisson regression analysis of grouped survival data, considering age, follow-up period, occupation and education. RESULTS: Bidi smoking was associated with GC risk (P = 0.042). The RR comparing current versus never smokers was 1.6 (95%CI: 1.0-2.5). GC risk was associated with the number of bidis smoked daily (P = 0.012) and with the duration of bidi smoking (P = 0.036). Those who started bidi smoking at younger ages were at an elevated GC risk; the RRs for those starting bidi smoking under the age of 18 and ages 18-22 were 2.0 (95%CI: 1.0-3.9) and 1.8 (95%CI: 1.1-2.9), respectively, when their risks were compared with lifetime non-smokers of bidis. Bidi smoking increased the risk of GC among never cigarette smokers more evidently (RR = 2.2; 95%CI: 1.3-4.0). GC risk increased with the cumulative amount of bidi smoking, which was calculated as the number of bidis smoked per day x years of smoking (bidi-year; P = 0.017). Cigarette smoking, tobacco chewing or alcohol drinking was not significantly associated with GC risk. CONCLUSION: Among a male cohort in South India, gastric cancer risk increased with the number and duration of bidi smoking.

Molecular Pathogenesis of Human Papillomavirus Type 16 in Tonsillar Squamous Cell Carcinoma.

AIM: The present study aimed to explore the etiological role of human papillomavirus (HPV) in tonsillar squamous cell carcinoma (TSCC). MATERIALS AND METHODS: HPV status, including viral load and E6 variants, and the expression of P53, p16(INK4A), and FANCD2, in tissues of TSCC (n=24) and tonsillitis (n=31) were investigated. RESULTS: The frequency of high-risk HPV (HPV-16) in TSCCs (42%) was higher than that of tonsillitis (16%). HPV-16 genome was partially or fully integrated in all HPV-16-positive TSCCs. However, the viral genome was partially integrated in three out of five HPV-16-positive tonsillitis cases (p=0.037). HPV-16-positive TSCCs showed a higher frequency of p16(INK4A) expression than HPV-16-negative TSCCs and tonsillitis (p=0.011). Regardless of HPV status, TSCCs had a lower expression of FANCD2 than tonsillitis (p=0.008). CONCLUSION: The present study supports the etiological role of HPV-16 in the development of TSCC, and p16(INK4A) overexpression can be applied as a surrogate marker for the detection of high-risk-HPV in TSCC.

Dose and dose-rate effects of ionizing radiation: a discussion in the light of radiological protection.

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection.

Long-term effects of radiation exposure on health.

Late-onset effects of exposure to ionising radiation on the human body have been identified by long-term, large-scale epidemiological studies. The cohort study of Japanese survivors of the atomic bombings of Hiroshima and Nagasaki (the Life Span Study) is thought to be the most reliable source of information about these health effects because of the size of the cohort, the exposure of a general population of both sexes and all ages, and the wide range of individually assessed doses. For this reason, the Life Span Study has become fundamental to risk assessment in the radiation protection system of the International Commission on Radiological Protection and other authorities. Radiation exposure increases the risk of cancer throughout life, so continued follow-up of survivors is essential. Overall, survivors have a clear radiation-related excess risk of cancer, and people exposed as children have a higher risk of radiation-induced cancer than those exposed at older ages. At high doses, and possibly at low doses, radiation might increase the risk of cardiovascular disease and some other non-cancer diseases. Hereditary effects in the children of atomic bomb survivors have not been detected. The dose-response relation for cancer at low doses is assumed, for purposes of radiological protection, to be linear without a threshold, but has not been shown definitively. This outstanding issue is not only a problem when dealing appropriately with potential health effects of nuclear accidents, such as at Fukushima and Chernobyl, but is of growing concern in occupational and medical exposure. Therefore, the appropriate dose-response relation for effects of low doses of radiation needs to be established.