RESUMEN
Epidemiological studies suggest that UV exposure from sunlight is the major etiology for skin cancers, both melanocytic and non-melanocytic. However, the radiation-related risk for skin cancer among atomic bomb survivors of Hiroshima and Nagasaki is primarily derived from the excess risk of basal cell carcinoma (BCC), with no demonstrable excess in squamous cell carcinoma or melanoma. The BCCs in this cohort are therefore unusual in being potentially attributable to two types of radiation-UV and ionizing (IR). BCCs have been associated with PTCH and/or p53 tumor suppressor gene alterations. To investigate the roles of these genes in relation to IR and UV exposures, we analyzed both genes in BCC samples from atomic bomb survivors. We examined 47 tumors, of which 70% had non-silent base-substitution p53 mutations independent of IR or UV exposure. However, the distribution of mutation type depends on UV and/or IR exposure. For example, C-to-T transitions at CpG sites adjacent to pyrimidine-pyrimidine (PyPy) sequences were more prevalent in tumors from UV-exposed than UV-shielded body areas and CpG-mutations at non-PyPy sequences were more prevalent in tumors from UV-shielded body areas with high-IR (>or=1 Gy) than low-IR (<0.2 Gy) exposure. And notably, although p53 deletion-frequencies demonstrated no IR-dose associations, deletions at the PTCH locus were more frequent (79% versus 44%) in tumors with high-IR than low-IR exposure. Moreover, 60% of high-IR tumors harbored both p53 and PTCH abnormalities compared with 23% of low-IR tumors. Therefore, alteration of both genes is likely to play a role in radiation-induced basal cell carcinogenesis.
Asunto(s)
Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Genes p53 , Neoplasias Inducidas por Radiación/genética , Ceniza Radiactiva/efectos adversos , Receptores de Superficie Celular/genética , Estudios de Cohortes , Islas de CpG , Humanos , Rayos Infrarrojos , Japón/epidemiología , Mutación , Guerra Nuclear , Receptores Patched , Receptor Patched-1 , Reacción en Cadena de la Polimerasa , Sobrevivientes , Rayos UltravioletaRESUMEN
PURPOSE: Although previous studies have shown significantly increased risks of liver cirrhosis and chronic liver disease for acute radiation exposure among survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, these studies have not taken into account hepatitis B virus (HBV) infections. Because HBV is associated with both A-bomb radiation and liver cirrhosis, our goal was to investigate the relationship of acute ionizing radiation to liver cirrhosis adjusting for HBV, co-occurring primary liver cancer (PLC), and other potential confounders. MATERIALS AND METHODS: Using a cross-sectional design and pathology review of a cohort of Japanese atomic-bomb survivors, we found that 213 of 335 (63.6%) subjects with PLC and 55 of 776 (7.1%) subjects without PLC had cirrhosis. RESULTS: We found no association between acute exposure to A-bomb radiation and liver cirrhosis. The adjusted odds ratio of cirrhosis per Sv liver irradiation was 0.59 (95% confidence interval: 0.27 - 1.27). Cirrhosis risks for the highest tertile of radiation exposure (mean exposure 0.7 Sv) were also not elevated (0.8, 0.26 - 2.12 and 0.2, 0.03 - 0.98 among subjects with and without PLC. CONCLUSIONS: Acute exposure to liver irradiation does not increase risks of liver cirrhosis, regardless of PLC status.
Asunto(s)
Exposición a Riesgos Ambientales/estadística & datos numéricos , Cirrosis Hepática/mortalidad , Guerra Nuclear/estadística & datos numéricos , Traumatismos por Radiación/mortalidad , Radiación Ionizante , Medición de Riesgo/métodos , Sobrevivientes/estadística & datos numéricos , Carga Corporal (Radioterapia) , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Femenino , Hepatitis B/mortalidad , Hepatitis C/mortalidad , Humanos , Incidencia , Japón/epidemiología , Masculino , Dosis de Radiación , Efectividad Biológica Relativa , Estudios Retrospectivos , Factores de Riesgo , Fumar/epidemiología , Estadística como AsuntoRESUMEN
To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case-control study within a cohort of Japanese A-bomb survivors. We compared the prediagnosis consumption of isoflavone-rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist-confirmed cases of HCC diagnosed in 1964-1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue-based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29-0.95) and 0.5 (95% CI 0.20-0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14-1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20-3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk.
Asunto(s)
Carcinoma Hepatocelular/dietoterapia , Hepatitis B/dietoterapia , Hepatitis C/dietoterapia , Neoplasias Hepáticas/dietoterapia , Alimentos de Soja , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Estudios de Casos y Controles , Estudios de Cohortes , Conducta Alimentaria , Hepacivirus/aislamiento & purificación , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Japón , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Factores de RiesgoRESUMEN
We conducted a nested case-control study within the cohort of Japanese survivors of the 1945 atomic bombings to study the joint effects of HBV and HCV with radiation on the risk of HCC. Among subjects who received autopsies during 1954-1988, we analyzed archival tissue samples for 238 pathologically confirmed HCC cases and 894 controls who died from diseases other than liver cancer. Using logistic regression and adjusting for potential confounders and other factors, we found a statistically significant, supermultiplicative interaction between A bomb radiation and HCV in the etiology of HCC. Compared to subjects who were negative for HCV and radiation, ORs of HCC for HCV-positive subjects showed a statistically significant, greater than multiplicative increase for liver irradiation exposures in the second (>0.018-0.186 Sv, p = 0.04) and third (>0.186 Sv, p = 0.05) tertiles of non-zero radiation exposure but not for first tertile exposure (>0-0.018 Sv, p = 0.86). Limiting analysis to subjects without cirrhosis, HCV-infected subjects were at 58.0-fold (95% CI 1.99- infinity ) increased risk of HCC per Sv of radiation exposure (p = 0.017), a supermultiplicative interaction between radiation and HCV that was not found among subjects with cirrhosis (p = 0.67). We found no evidence of interaction between HBV infection and radiation exposure in the etiology of HCC, regardless of cirrhosis status (p = 0.58). We conclude that among survivors of the nuclear bombings of Hiroshima and Nagasaki, subjects who were both HCV-positive and radiation-exposed were at a significantly, supermultiplicatively increased risk of HCC without concurrent cirrhosis.