Ionizing radiation exposure and the development of soft-tissue sarcomas in atomic-bomb survivors

BACKGROUND: Very high levels of ionizing radiation exposure have been associated with the development of soft-tissue sarcoma. The effects of lower levels of ionizing radiation on sarcoma development are unknown. This study addressed the role of low to moderately high levels of ionizing radiation exposure in the development of soft-tissue sarcoma. METHODS: Based on the Life Span Study cohort of Japanese atomic-bomb survivors, 80,180 individuals were prospectively assessed for the development of primary soft-tissue sarcoma. Colon dose in gray (Gy), the excess relative risk, and the excess absolute rate per Gy absorbed ionizing radiation dose were assessed. Subject demographic, age-specific, and survival parameters were evaluated. RESULTS: One hundred and four soft-tissue sarcomas were identified (mean colon dose = 0.18 Gy), associated with a 39% five-year survival rate. Mean ages at the time of the bombings and sarcoma diagnosis were 26.8 and 63.6 years, respectively. A linear dose-response model with an excess relative risk of 1.01 per Gy (95% confidence interval [CI]: 0.13 to 2.46; p = 0.019) and an excess absolute risk per Gy of 4.3 per 100,000 persons per year (95% CI: 1.1 to 8.9; p = 0.001) were noted in the development of soft-tissue sarcoma. CONCLUSIONS: This is one of the largest and longest studies (fifty-six years from the time of exposure to the time of follow-up) to assess ionizing radiation effects on the development of soft-tissue sarcoma. This is the first study to suggest that lower levels of ionizing radiation may be associated with the development of soft-tissue sarcoma, with exposure of 1 Gy doubling the risk of soft-tissue sarcoma development (linear dose-response). The five-year survival rate of patients with soft-tissue sarcoma in this population was much lower than that reported elsewhere.published_or_final_versio

Bone sarcomas in atomic bomb survivors of Hiroshima and Nagasaki

Abstract no. 1017PURPOSE/OBJECTIVE(S): Ionizing radiation‐induced bone sarcomas have traditionally been associated with exposure to high levels of ionizing radiation. The role of exposure to lower levels of ionizing radiation in the development of such lesions remains speculative. Also, the appropriate dose‐response model of radiation dose exposure to excess relative risk (ERR) in association with bone sarcomas is questionable. MATERIALS/METHODS: The data source of the longitudinal, population‐based Life Span Study (N=120,321) cohort of atomic bomb survivors of Hiroshima and Nagasaki was utilized to estimate the ERR per Gray (Gy) of ionizing radiation exposure in the development of bone sarcomas. Other factors regarding sarcoma demographics …postprin

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women : reanalysis of eighteen prospective studies

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes