Suminori Akiba

Incidence of female breast cancer among atomic bomb survivors, 1950-1985

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose

Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the hombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor—age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births—conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early agefollowing exposure may be protective against radiation-related risk.

Serum ferritin and stomach cancer risk among a Japanese population.

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970‐to‐1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

A case-control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects

Women with breast cancer (cases=196) and without the disease (controls=566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]2) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations.

Prospective cohort study of risk factors for primary liver cancer in Hiroshima and Nagasaki, Japan.

We investigated risk factors for primary liver cancer among a cohort of 36,133 residents in Hiroshima and Nagasaki, Japan, originally established to examine the association between exposure to atomic bomb radiation and disease. A mail survey to study the late effects of atomic bomb radiation was conducted among the cohort between 1978 and 1981. During the subsequent follow-up period (average 8.61 years), 242 cases of primary liver cancer were identified through population-based tumor registries in the two cities. The relative risk (RR) of liver cancer was 2.23 [95% confidence interval (CI) = 1.53–3.23] for tobacco smokers compared with those who had never smoked. Alcohol use was slightly positively associated with the risk of liver cancer, and men who had quit drinking had an RR of 2.33 (95% CI = 1.34–4.07) compared with those who never drank. Among alcohol drinkers, an inverse relation between years of abstinence and the rate of liver cancer was found, possibly attributable to a confounding effect of preclinical disease. The use of female hormone preparations was modestly associated with the risk of liver cancer (RR = 1.29; 95% CI = 0.59–2.84). Other risk factors included a self-reported history of radiation therapy (RR = 1.79; 95% CI = 1.34–2.40) and a history of diabetes mellitus (RR = 1.79; 95% CI = 1.31–2.43).

The observed relationship between the occurrence of acute radiation effects and leukemia mortality among A-bomb survivors.

In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb survivors in Hiroshima and Nagasaki, the slope of an estimated dose response between ionizing radiation and leukemia mortality was found to be steeper (P less than 0.002), by a factor of 2.4, among those who reported epilation within 60 days of the bombings, compared to those who did not experience this sign of acute radiation exposure. The strength of this empirical finding as evidence of biological association in individual radiosensitivity for these two end points is studied here. The major factor complicating the interpretation of this finding as evidence of such an association is the degree of imprecision of the radiation dosimetry system used in assignment of radiation doses to the A-bomb survivors. Using models recently suggested for dealing with dosimetry errors in epidemiological analysis of the A-bomb survivor data, the sensitivity of the apparent association between leukemia mortality and severe epilation to the assumed level of dosimetry error is investigated.

Prevalence of Hepatitis B Surface Antigen, Hepatitis B e Antigen and Antibody, and Antigen Subtypes in Atomic Bomb Survivors

On the basis of previous studies showing an association between hepatitis B surface antigen (HBsAg) positivity and radiation exposure in atomic bomb (A-bomb) survivors, we investigated further the active state of hepatitis B virus (HBV) infection by incorporating tests for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) and HBsAg subtypes into our biennial health examinations. Among 6548 A-bomb survivors for whom HBsAg was assayed between July 1979 and July 1981, 129 persons were HBsAg positive. HBeAg and anti-HBe were measured in 104 of these persons and subtypes of HBsAg in 98 persons. Among those exposed to radiation (average liver dose 0.58 Sv), the odds ratio of HBsAg positivity tended to increase with radiation dose (P for trend = 0.024). The P values for association between the prevalence of HB e antigen and radiation dose and between the prevalence of anti-HBe and radiation dose were 0.094 and 0.17, respectively. The HB antigen subtype adr was predominant over other subtypes in both Hiroshima and Nagasaki, but the distribution of subtypes did not seem to differ in relation to radiation dose. These results suggested that A-bomb survivors remain in an active state of HBV infection and that the mechanism(s) of seroconversion may be impaired.

A 50-Year Projection of Lung Cancer Deaths among Japanese Males and Potential Impact Evaluation of Anti-smoking Measures and Screening Using a Computerized Simulation Model

The lung cancer death rate among Japanese males was projected for 50 years to the year 2041 by a computerized simulation model. Long‐term effects of anti‐smoking measures and mass screening on lung cancer deaths were also evaluated. The simulation showed that the age‐adjusted lung cancer death rate would increase and reach a peak of 166 per 100,000 in 1989 and then decrease to 148 per 100,000 in 2003. It then shows an increasing tendency again, up to 255 per 100,000 in 2028. The smoking initiation rates estimated from the observed lung cancer death rates showed that the changes in death rates may be attributed to a lower smoking initiation rate among those born in the 1930s. Promotion of mass screening programs is effective more quickly than anti‐smoking measures but the reduction in annual cancer deaths is expected to be only 11%, even if 100% participation is achieved by the year 2000. A reduction in smoking initiation rate, on the other hand, affects lung cancer deaths very slowly. It was predicted that a 1% annual reduction in smoking initiation rate would result in a 20% decrease in the number of lung cancer deaths in 2041. A smoking cessation program is intermediate with regard to promptness. The predicted reductions in lung cancer deaths in 2041 were 13%, 47%, and 66%, respectively, when the annual smoking cessation rate was increased from 0.46% (present status) to 1%, 3%, and 5%. In conclusion, the combined application of all three preventive measures seems essential to realize the most effective reduction in lung cancer deaths.

Smoking and lung cancer mortality in Japanese men: estimates for dose and duration of cigarette smoking based on the Japan vital statistics data.

For the purpose of understanding human carcinogenesis and making a quantitative prediction of lung cancer mortality in a general population of Japanese males, we evaluated a statistical model which assumes lung cancer mortality to be proportional to the 4.5th power of the effective duration of cigarette smoking among smokers and to the 4th power of age among nonsmokers, using Japan Vital Statistics data. For the male birth cohorts aged 30–69 in 1965 in the age range of 40–79, studied by quinquennial calendar time intervals from 1955 to 1985, it was found that, (i) for nonsmokers, the estimated lung cancer mortality rate was comparable to the rates reported in the US or Britain, assigning 20 to 25% proportions of nonsmokers, (ii) for smokers, the estimated duration of smoking was shorter than would be expected from the age when smoking was started according to various epidemiological surveys, and (iii) the estimated average numbers of cigarettes smoked per day by smokers were similar to those obtained by epidemiological studies, when these were estimated by incorporating a part of Doll and Petos dose‐response relationship. Also discussed is the possibility of assessing lung cancer mortality risk for Japanese male smokers by means of the statistical model, a × (cigarettes smoked per day +β) × (age— (age started smoking) —γ)4,s.