Human infections with Borrelia miyamotoi, Japan.

We confirmed infection of 2 patients with Borrelia miyamotoi in Japan by retrospective surveillance of Lyme disease patients and detection of B. miyamotoi DNA in serum samples. One patient also showed seroconversion for antibody against recombinant glycerophosphodiester phosphodiesterase of B. miyamotoi. Indigenous relapsing fever should be considered a health concern in Japan.

Papillary microcarcinoma of the thyroid among atomic bomb survivors: tumor characteristics and radiation risk.

BACKGROUND: : Radiation exposure is an established cause of clinical thyroid cancer, but little is known about radiation effects on papillary microcarcinoma (PMC) of the thyroid, a relatively common subclinical thyroid malignancy. Because the incidence of these small thyroid cancers has been increasing, it is important to better understand them and their relation to radiation. METHODS: : PMCs were identified in a subset of 7659 members of the Life Span Study of atomic bomb survivors who had archived autopsy or surgical materials. We conducted a pathology review of these specimens and evaluated the histological features of the tumors and the association between PMCs and thyroid radiation dose. RESULTS: : From 1958 to 1995, 458 PMCs were detected among 313 study subjects. The majority of cancers exhibited pathologic features of papillary thyroid cancers. Overall, 81% of the PMCs were of the sclerosing variant and 91% were nonencapsulated, psammoma bodies that occurred in 13% and calcification was observed in 23%. Over 95% had papillary or papillary-follicular architecture and most displayed nuclear overlap, clear nuclei, and nuclear grooves. Several of these features increased with increasing tumor size, but no association was found with radiation dose. A significant radiation-dose response was found for the prevalence of PMCs (estimated excess odds ratio/Gy = 0.57; 95% confidence interval, 0.01-1.55), with the excess risk observed primarily among women. CONCLUSIONS: : Exposure to low-to-moderate doses of ionizing radiation appears to increase the risk of thyroid PMCs, even when exposure occurs during adulthood. Cancer 2010. (c) 2010 American Cancer Society.

The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose.

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.

Lifestyle factors, radiation and gastric cancer in atomic-bomb survivors (Japan).

OBJECTIVE: To examine the association between the incidence of gastric cancer and lifestyle factors such as cigarette smoking, alcohol drinking, and diet as well as atomic bomb radiation exposure. METHODS: Longitudinal study including 38,576 atomic-bomb survivors in Hiroshima and Nagasaki, Japan, followed-up between 1980 and 1999. Individual radiation dose was estimated according to the Dosimetry System 1986 (DS86). Lifestyle determinants were based on the responses to a mail survey sent at baseline. 1270 incident carcinomas of gastric cancer were identified during the 485,575 person-years of follow-up. Poisson regression was used to estimate incidence rate ratios. RESULTS: Ionizing radiation exposure, male gender, age, and smoking were significantly associated with an increased risk of stomach cancer. No association was suggested between the frequency of consumption of fruit, vegetables, green tea, and soy products and gastric cancer. CONCLUSIONS: In this Japanese population, although radiation and smoking were strong determinants of stomach cancer, no supportive evidence could be shown for the effect of dietary factors.

Histologic characteristics of skin cancer in Hiroshima and Nagasaki: background incidence and radiation effects.

Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic-bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population-based study of spontaneous as well as radiation-related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic-bomb radiation exposure did not differ between UV-exposed and shielded parts of the body, suggesting the additivity of the radiation-related and background BCC risks.

A prospective study of diet and prostate cancer in Japanese men.

BACKGROUND AND AIMS: It has been hypothesized that some aspect of a traditional 'Asian' diet, that is low in animal products and high in soya, may be associated with a reduced risk of prostate cancer. This study aimed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study. METHODS: Subjects completed a food-frequency questionnaire at baseline (1963, 1965 and/or 1979) and were followed for incident prostate cancer until the end of 1996. During this time, 196 incident prostate cancer cases were identified after 252,602 person-years of observation. Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age, calendar period, city of residence, radiation dose and education level. RESULTS: Fish intake was significantly associated with an increased risk of prostate cancer; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week (RR = 1.54; 95% CI, 1.03-2.31). No other food items, including soya products, were significantly associated with prostate cancer risk. CONCLUSIONS: These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men, although the increased risk associated with a high consumption of fish warrants further study.

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990.

An incidence survey of the Life Span Study (LSS) population found 1093 breast cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier breast cancer surveys of this population, a linear and statistically highly significant radiation dose response was found. In the analysis, particular attention was paid to modification of radiation dose response by age at exposure (e) and attained age (a). Dose-specific excess relative risk (ERR(1Sv)) decreased with increasing values of e and a. A linear dose-response model analysis, with e and a as exponential age modifiers, did not conclusively discriminate between the two variables as modifiers of dose response. A modified isotonic regression approach, requiring only that ERR(1Sv) be monotonic in age, provides a fresh perspective indicating that both e and a are important modifiers of dose response. Exposure before age 20 was associated with higher ERR(1Sv) compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR(1Sv) was observed to decline with increasing attained age, with by far the largest drop around age 35. Possible explanations for these observations are discussed, along with research approaches that might provide more information.

Radiation-related mortality among offspring of atomic bomb survivors: a half-century of follow-up.

Our objective was to examine whether parental exposure to atomic bomb radiation has led to increased cancer and/or noncancer mortality rates among the offspring. We studied 41,010 subjects born from May 1946 through December 1984 (i.e., conceived between 1 month and 38 years after the bombings) and surviving for at least 1 year. One or both parents were in Hiroshima or Nagasaki at the time of the bombings and childbirth. We analyzed mortality data from 1946 to 1999 using the Japanese family registry system by Cox regression model and examined the effects of paternal and maternal irradiation with adjustment for city, sex, year of birth and parental age at childbirth. During follow-up, 314 cancer deaths and 1,125 noncancer disease deaths occurred. The mean age of living subjects was 45.7 years. Median doses were 143 mSv for 12,722 exposed fathers and 132 mSv for 7,726 exposed mothers. Cancer and noncancer mortality rates were no higher for subjects with exposed parents (5+ mSv or unknown dose) than for reference subjects (0-4 mSv), and mortality did not increase with increasing dose. For subjects with both parents exposed, the adjusted hazard ratios were 1.16 [95% confidence interval (CI) 0.92-1.46] for noncancer and 0.96 (95% CI 0.59-1.55) for cancer. This was true of deaths occurring both before and after 20 years of age. However, because of uncertainty due to the small number of deaths and relatively young ages of subjects, we cannot rule out an increase in disease mortality at this time.