The risk of non-melanoma skin cancer incidence in the Japanese atomic bomb survivors

The latest Japanese atomic bomb survivor non-melanoma skin cancer incidence dataset is analysed and indicates substantial curvilinearity in the dose-response curve, consistent with a possible dose threshold of about 1 Sv, or with a dose-response in which the excess relative risk is proportional to the fourth power of dose, with a turning-over in the dose-response at high doses (> 3 Sv). The time distribution of the radiation-induced excess risk is best described by a model in which the relative excess risk is proportional to a product of powers of time since exposure and attained age. The fits of generalized relative risk models with exponential functions of time and age at exposure (and in particular of attained age) to adjust the relative risk are less satisfactory, as also are the fits of other models in which products of powers of time since exposure, age at exposure and attained age adjust the excess absolute risk. Sensitivity analyses indicate the importance of likely adjustments to the Hiroshima neutron doses for the optimal model parameters, particularly if values of the neutron relative biological effectiveness (RBE) of more than 5 are assumed. If adjustments recently proposed are made to the Hiroshima neutron doses, then using the optimal model (in which excess risk is proportional to the fourth power of dose) the best estimate of the neutron RBE is 1.3 (95% CI < 07.1). However, uncertainties in skin dose estimates for the atomic bomb survivors means that the findings with respect to the neutron RBE and the non-linearity in the dose-response curve should be treated with caution.     

Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki

Occupational asthma is the most common occupational lung disease in the world. Occupational asthma comprises approximately 25-50% of occupational lung diseases and is responsible for up to 15% of all asthma cases. Either immunologic or nonimmunologic causes may be responsible for occupational asthma. There are approximately 250 compounds known to cause occupational asthma. Common examples include flour, animal dander, isocyanates, and latex. The diagnosis of occupational asthma depends on an accurate history of asthma and documentation that the asthma is caused by workplace exposure. Peak flow measurements are commonly used to provide data to define this relationship. Spirometry and bronchial provocation testing are also helpful. The key management tool in occupational asthma is avoidance of the causative agent. Avoidance is more important than treatment with medications. Occupational asthma can have major socioeconomic impacts on an individual, and the diagnostic work-up and management needs to be performed with this in mind.     

Radiosensitivity of atomic bomb survivors as determined with a micronucleus assay

We have developed a system in which a unique double-stranded break (DSB) can be introduced into a yeast chromosome during mitotic growth. The recognition site for the endonuclease I-SceI was inserted at different places in the yeast genome in haploid and diploid cells expressing this endonuclease. Induction of the break in haploids results in cell death if no intact copy of the cleaved region is present in the cell. If such a copy is provided on a plasmid, as an ectopic gene duplication, or on a homologous chromosome, the break can be repaired. Repair results in two identical copies in the genome of the locus which has been cut. We call this phenomenon homozygotization by reference to diploids heterozygous for the cut site in which repair leads to homozygosis at this site. We have compared the efficiencies of repair in the various topological situations examined, and conclude that some mechanism must search for regions of homology to both sides of the DSB and that repair is successful only if the homologies are provided by the same template molecule.     

Benign tumors of the digestive tract among atomic bomb survivors, 1961-1970 Hiroshima

The occurrence of benign tumors and diverticular of the digestive tract was investigated in an autopsy study of a fixed population of 100,000 samples in Hiroshima and Nagasaki. There were 664 benign tumors and 40 diveritcula. Polyps were the most frequent tumor, were found more often in older people, occurred as single pedunculated well-differentiated adenomatous tumors, and most were less than 5 mm in greatest dimension. Larger polyps tended to have more atypism, but none showed definite premalignant change. No transition from benign to malignant polyps was seen. Polyps were found most frequently in the large intestine and in a large number (21%) and, when cancer of the large intestine was present, benign polyps were also found. Far more polyps are found when special intensive search is made for them. Comparison of the occurrence of benign polyps in different geographic areas must be adjusted for age and method of search as well as for other features such as histological type, dysplasia, etc. There was no evidence that the occurrence of benign tumors or diveritcula was related to prior exposure to ionizing radiation.     

Evaluation of possible population bias among high-dose atomic bomb survivors in the frequency of the HLA-DQA1 allele and DR antigen types

Many studies have suggested a relationship between certain alleles of the human leukocyte antigen (HLA) and the prevalence of some diseases or the immunological responsiveness to certain antigens. Furthermore, our studies in the past have demonstrated decreased immune function among atomic-bomb survivors who were exposed to high doses of radiation. However, no studies have addressed the possibility of various degrees of radiation-induced immune suppression being dependent on HLA type. To investigate the possibility of differing frequency distributions of HLA type in the Hiroshima atomic bomb survivors, HLA-DQA1 alleles and HLA-DR antigens were typed for 291 survivors in a high-dose group (>1.5 Gy), 339 survivors in an intermediate-dose group (0.005-1.5 Gy), and 388 in a distally exposed control group (<0.005 Gy). These doses are whole-body exposures, mainly from gamma-rays but with a small neutron component. When examinees were grouped by distinct pairs of HLA-DQA1 allele or HLA-DR antigen, no sex- or dose-related differences were found. However, when subjects were grouped by the presence of a specific allele or antigen, males carrying DQA1*0103 in at least one of their two HLA-DQA1 loci exhibited frequency distributions that decreased as radiation dose increased. These results suggest, although weakly, a possible population bias among male survivors with respect to HLA polymorphism. However, this bias is unlikely to be great enough to have a substantial effect on the cancer risk estimates.     

Cancer mortality among atomic bomb survivors exposed in utero or as young children, October 1950-May 1992

Improvements in workplace health among silica exposed workers followed demonstrations of the severity of the risk of silicosis and means of controlling high dust levels on the job. Current ambient environmental analyses include either an adoption of air quality goals for reducing emissions of criteria pollutants or the conduct of risk assessments to determine if regulatory procedures are needed. Although silica has been regulated as a workplace hazard for most of the 20th century, only recently has it been considered for ambient control, and most of the thrust for this action has evolved from environmental regulatory work in California, where both state initiative (Proposition 65) and legislative law (Air Toxics Hot Spots Information and Assessment Act; Assembly Bill number 2588) have required risk assessments for silica dust emissions as carcinogens.     

Predicting posttraumatic growth in breast cancer survivors.

Wide variability exists with respect to how breast cancer survivors respond to common psychological and psychosocial challenges of their disease, ranging from posttraumatic stress disorder to posttraumatic growth. This cross-sectional study examined contextual, disease-related, and intraindividual predictors of posttraumatic growth in 224 randomly selected breast cancer survivors. A series of hierarchical regression analyses found that age at diagnosis, marital status, employment, education, perceived intensity of disease, and active coping accounted for 34%, 35%, and 28% of the variance in growth in relationships with others, new possibilities, and appreciation for life. These findings suggest that a more comprehensive model of growth will be helpful in understanding the various factors that play a role in breast cancer survivors' perception of psychological and psychosocial growth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

p53 mutations and overexpressions in Japanese breast cancer

In this paper, we explore the use of a variety of familial transmission tests (and case-control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5-10 years. We demonstrate a form of the transmission-disequilibrium test extended to multiallele systems. The methods used were log-linear and related models implemented largely using standard statistical packages.     

Diet and breast cancer risk in a cohort of Finnish women

The associations between dietary antioxidant vitamins, dietary fiber, and selected foods and risk of breast cancer were studied in 4697 initially cancer-free women, aged 15 years or older. At baseline (1967-1972) the women were interviewed for total habitual diet over the preceding year. During a 25-year follow-up period 88 breast cancer cases were diagnosed. There was a significant inverse gradient between milk consumption and occurrence of breast cancer, whereas higher consumption of fried meat was associated with increased risk of breast cancer. No significant relationships were found between the intakes of vitamin E, vitamin C, beta-carotene, lycopene, lutein or dietary fiber and the occurrence of breast cancer.     

Quality of life and breast cancer survivors. Psychosocial and treatment issues

Vitamin A deficiency is one of the most common nutrient deficiency syndromes in children from developing countries. It is also correlated with the increased severity and incidence of certain infections. Until recently, vitamin A research was focused on preventing xerophthalmia and blindness in Third World Countries and on the development of synthetic retinoid molecules, with lower toxicity than vitamin A, for the treatment of skin diseases. However, there has been a major shift of emphasis in the last five to ten years. There is a risk of death from xerophthalmia, primarily from complications with infectious diseases. Intermittent treatment with the very large doses of vitamin A prescribed to combat blindness was shown to be effective. This suggests that vitamin A may affect specific elements of the immune system. High-dose vitamin A supplements have been given, at widely-spaced time intervals, to preschool children in communities where vitamin A deficiency causes xerophthalmia and blindness, over the last 20 to 30 years. A strong correlation between mortality and xerophthalmia was identified. Death then became the principal outcome measured because it was easier to detect than xerophthalmia, particularly in large clinical trials in high risk regions where clinical expertise was minimal and vitamin A deficiency was a commoner cause of death than blindness. Other, food-based approaches to the treatment and prevention of vitamin A deficiency, involving foods naturally rich in retinol or carotenoid, or foods artificially fortified with these nutrients, should be developed.     

Statistical modelling of breast cancer incidence and mortality rates in Scotland

The interpretation of time trends in disease rates can be facilitated using estimable contrasts from age-period-cohort models. Cohort and period trends in breast cancer incidence and mortality rates in Scotland were investigated using contrasts that measure the changes in the linear trends. These contrasts were compared with estimates obtained from mortality rates in the USA and Japan. A significant moderation of both breast cancer incidence and mortality rates was observed in Scotland, associated with cohorts of women born after the Second World War compared with women born between the two world wars. The moderation of breast cancer mortality among cohorts born after 1925 compared with cohorts born before 1925 that was observed in the USA and Japan was also observed in this study. This moderation is not present in the incidence rates. The relative decline in the risk of breast cancer seen in younger cohorts seems to be contradictory to the temporal pattern present among breast cancer risk factors. It may well be that the alteration of eating patterns as a result of rationing in the wartime and immediate post-war period, and the subsequent influence on certain breast cancer risk factors probably produced by such changes, may have had some influence on the development of healthier girls and women. Such speculation could be addressed in a well-designed epidemiological study. There have been no changes in the mortality rate trends with period in Scotland, although the changes in the incidence rate trends with period are consistent with an increase in registration coverage.     

Self-selection for mammography and breast cancer incidence by stage

AIMS AND BACKGROUND: In the field of breast cancer control, obtaining population-based data on spontaneous mammography (MG) screening should be a priority. This study focuses on the breast cancer incidence and stage distribution in relation to MG use in Ravenna (Italy), 1987-88. METHODS: We estimated the MG rates, expected (E) incidence based on mortality data, observed (O) incidence, predicted excess incidence based on MG rates, observed excess incidence, and stage distribution according to the MG history. RESULTS: The highest MG rate (37%) was found among residents aged 40-44 but none of these had a T1a-bNO breast cancer diagnosed nor was the predicted excess incidence demonstrated. Between 45 and 64 years, 80% of self-selected screenees had repeat ("incidence") MG and the O:E incidence ratio was 1.32 (95% CI 1.09-1.58). The observed excess incidence was 3.8-fold (95% CI 2.56-5.16) greater than that predicted. Advanced (T2+ and/or N1+) cases accounted for 42% of patients diagnosed within 3 years of their last MG, for 55% of those diagnosed more than 3 years after their last MG, and for 70% of those with no previous MG. Above age 70, a significant worsening of stage at diagnosis was associated with a clearcut drop self-referral for MG. CONCLUSIONS: The results indicate that self-selection and its implications are major features of spontaneous screening practice.     

Prospective evaluation of vitamin E for hot flashes in breast cancer survivors

PURPOSE: Hot flashes represent a substantial clinical problem for some breast cancer survivors. Although estrogen or progesterone preparations can alleviate these symptoms in many patients, concern remains regarding the use of hormonal preparations in such women. Thus, there is a perceived need for nonhormonal treatments for hot flashes for breast cancer survivors. Based on anecdotal evidence that vitamin E was helpful, we designed a trial to investigate this matter. METHODS: We developed and conducted a placebo-controlled, randomized, crossover trial where, after a 1 week baseline period, patients received 4 weeks of vitamin E 800 IU daily, then 4 weeks of an identical-appearing placebo, or vice versa. Diaries were used to measure potential toxicities and hot flashes during the baseline week and the two subsequent 4-week treatment periods. RESULTS: The 120 patients evaluated for toxicity failed to show any. The 105 patients who finished the first treatment period showed a similar reduction in hot flash frequencies (25% v 22%; P = .90) for the two study arms. A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (P < or = .05). At the study end, patients did not prefer vitamin E over the placebo (32% v 29%, respectively). CONCLUSION: Although this trial was able to show a statistically significant hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal.     

Occupation and breast cancer mortality in a prospective cohort of US women

We report the isolation of the functional form of the Ca-ATPase from porcine cardiac sarcoplasmic reticulum (SR) membranes, taking advantage of the ability of this enzyme to bind to the nucleotide site affinity dye, Reactive Red 120. Conditions that optimize the solubility and functional stability of the cardiac Ca-ATPase in detergent during the purification procedure are essential to its recovery. The purified Ca-ATPase migrates as a single band on Coomassie blue-stained polyacrylamide gels and exhibits high specific activity (2.5 IU at 25 degreesC) and functional stability. Similar enrichment of the Ca-ATPase estimated from either relative amounts of the 100-kDa protein band on polyacrylamide gels or steady-state concentrations of phosphorylated enzyme intermediate (E-P) demonstrate that neither nonfunctional Ca-ATPases nor non-Ca-ATPase proteins migrating with an apparent molecular weight of 100 kDa constitute a significant fraction of these preparations. Steady-state levels of E-P are 1.3 and 8.6 nmol/mg protein, respectively, for native cardiac SR membranes and the final purified fraction. These values, in comparison to the maximum value (9.1 nmol/mg) for the 110-kDa protein, agree well with estimates of total Ca-ATPase abundance from gel densitometry for both preparations and indicate full site reactivity, i.e., one phosphorylation site for each 110-kDa cardiac Ca-ATPase polypeptide chain.     

Social support as a mediator of optimism and distress in breast cancer survivors.

Breast cancer patients can experience emotional distress as a result of diagnosis and treatment. Higher levels of optimism and social support are associated with less emotional distress in cancer patients. This 12-month prospective study followed 69 women who had completed treatment for Stages 0-11 breast cancer. At 3-month intervals, participants completed measures of mood disturbance, optimism, and social support. As hypothesized, affective social support mediated the relationship between optimism and distress in early-stage breast cancer survivors at baseline and 6 months but not at 1 year. In contrast, confidant social support did not mediate the optimism-distress relationship at any time point. Clinical and research implications of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mortality and incidence of cancer among sewage workers: a retrospective cohort study

To study the incidence of and mortality from cancer among sewage workers a retrospective analysis was performed on a cohort of 656 men employed for at least one year at any one of 17 Swedish sewage plants during the years 1965-86. Assessment of exposure was done by classification of work tasks. Lower than expected total mortality (standardised mortality ratio (SMR) = 0.75, 95% confidence interval (95% CI) 0.58-0.97) and cardiovascular mortality (SMR = 0.61, 95% CI 0.39-0.91) was found. This was interpreted as a result of the healthy worker effect. For all cancers combined the mortality (SMR = 1.08, 95% CI 0.68-1.67) and morbidity (SMR = 1.02, 95% CI 0.72-1.38) were comparable with those of the general population. There were increased incidences for brain tumours (SMR = 2.19, 95% CI 0.45-6.39), gastric cancers (SMR = 2.73, 95% CI, 1.00-5.94), and renal cancers (SMR = 1.68, 95% CI = 0.35-4.90). For lung cancer the risk was reduced (SMR = 0.70, 95% CI 0.15-2.05). Allowance for a latency period of 10 years from the start of exposure did not change the pattern. Logistic modelling was used to search for exposure-response relations. In a logistic model with the confounder age forced in, renal cancer had a significant positive relation with a weighted sum of employment times, where the weights describe the classification of exposure. No exposure-response relations were found for brain tumors or gastric cancers. The increased risks are based on small numbers of cases. A future follow up will add more conclusive power to the study. Specific exposures need to be identified to allow for a better dose-response analysis.