Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

BACKGROUND: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. METHODS: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. RESULTS: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. CONCLUSION: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

Body mass index and lung cancer risk: Pooled analysis of 10 prospective cohort studies in Japan.

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta-analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I2statistics. During 5,730,013 person-years of follow-up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16-1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71-0.84) and 0.69 (95% CI, 0.45-1.07), respectively. Every 5 kg/m2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75-0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers.

The Effect of Prostate-Specific Antigen (PSA) Test on Radiation Risk Estimate for Prostate Cancer Incidence among Atomic-Bomb Survivors.

Following our previous report on the radiation dose-response for prostate cancer incidence rates in the Life Span Study (LSS) cohort of atomic bomb survivors, we reevaluated the radiation-related risk adjusting for differences in baseline cancer incidence rates among three subsets of the LSS cohort defined by the timing of their first participation in biennial health examinations offered to the Adult Health Study (AHS) sub-cohort members and prostate-specific-antigen (PSA) testing status for AHS participants: 1. non-AHS participants, 2. AHS participants before receiving PSA test, and 3. AHS participants after receiving PSA test. We found a 2.9-fold increase in the baseline incidence rates among AHS participants after receiving PSA test. After adjusting for the PSA-testing-status effects on the baseline rates the estimated excess relative risk (ERR) per Gy was 0.54 (95% CI: 0.15, 1.05), which was almost identical to the previously reported unadjusted ERR estimate (0.57, 95% CI: 0.21, 1.00). The current results confirmed that, while the PSA testing among AHS participants increased the baseline incidence rates, it did not impact the radiation risk estimate, strengthening the previously reported dose-response relationship for prostate cancer incidence in the LSS. As the use of PSA tests continue in screening and medical settings, analyses of possible effects of PSA testing should be an important aspect of future epidemiological studies of the association between radiation exposure and prostate cancer.

Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan.

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m2 increase 0.57, 95% CI 0.50-0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00-1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m2 ) relative to BMI <25 kg/m2 was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80-2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05-1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study-the largest in an Asian country-provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.

Age effects on radiation response: summary of a recent symposium and future perspectives.

One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3-6 October 2021.

Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies.

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large-scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study-specific HRs using a random-effects model. During 4 265 551 person-years of follow-up, 8586 stomach cancer cases were identified. In men, the multivariate-adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87-1.15) for occasional drinkers, and 1.00 (0.91-1.11) for <23 g/d, 1.09 (1.01-1.18) for 23 to <46 g/d, 1.18 (1.09-1.29) for 46 to <69 g/d, 1.21 (1.05-1.39) for 69 to <92 g/d, and 1.29 (1.11-1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate-adjusted HRs were 0.93 (0.80-1.08) for occasional drinkers, and 0.85 (0.74-0.99) for <23 g/d, and 1.22 (0.98-1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/d in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.

Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan.

BACKGROUND: Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood. METHODS: We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983-1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model. RESULTS: The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1-10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose-response manner. HRs (95% CIs) were 1.27 (0.97-1.66), 1.45 (1.33-1.59) and 1.49 (1.38-1.62) for 1-2, 3-5 and 6-10 CPD, respectively, in men; 1.28 (1.01-1.62), 1.49 (1.34-1.66) and 1.68 (1.55-1.81) for 1-2, 3-5 and 6-10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk. CONCLUSIONS: Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD.

Effects of Helicobacter pylori eradication on gastric cancer incidence in the Japanese population: a systematic evidence review.

BACKGROUND: In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions. METHODS: We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention). RESULTS: In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall odds ratio of 0.34 (95% CI: 0.25-0.46). Regarding tertiary prevention, the overall odds ratio for developing metachronous gastric cancer was 0.42 (95% CI: 0.35-0.51) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection. CONCLUSION: H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.

Impact of reproductive factors on breast cancer incidence: Pooled analysis of nine cohort studies in Japan.

Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional-hazards model in each study. These hazard ratios were integrated using a random-effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04-2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21-25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26-35 years experienced significantly higher BC incidence than at ages 21-25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.

Mortality among individuals exposed to atomic bomb radiation in utero: 1950-2012.

We examined the mortality risks among 2463 individuals who were exposed in utero to atomic bomb radiation in Hiroshima or Nagasaki in August 1945 and were followed from October 1950 through 2012. Individual estimates of mother's weighted absorbed uterine dose (DS02R1) were used. Poisson regression method was used to estimate the radiation-associated excess relative risk per Gy (ERR/Gy) and 95% confidence intervals (CI) for cause-specific mortality. Head size, birth weight, and parents' survival status were evaluated as potential mediators of radiation effect. There were 339 deaths (216 males and 123 females) including deaths from solid cancer (n = 137), lymphohematopoietic cancer (n = 8), noncancer disease (n = 134), external cause (n = 56), and unknown cause (n = 4). Among males, the unadjusted ERR/Gy (95% CI) was increased for noncancer disease mortality (1.22, 0.10-3.14), but not for solid cancer mortality (- 0.18, < - 0.77-0.95); the unadjusted ERR/Gy for external cause mortality was not statistically significant (0.28, < - 0.60-2.36). Among females, the unadjusted ERRs/Gy were increased for solid cancer (2.24, 0.44-5.58), noncancer (2.86, 0.56-7.64), and external cause mortality (2.57, 0.20-9.19). The ERRs/Gy adjusted for potential mediators did not change appreciably for solid cancer mortality, but decreased notably for noncancer mortality (0.39, < - 0.43-1.91 for males; 1.48, - 0.046-4.55 for females) and external cause mortality (0.10, < - 0.57-1.96 for males; 1.38, < - 0.46-5.95 for females). In conclusion, antenatal radiation exposure is a consistent risk factor for increased solid cancer mortality among females, but not among males. The effect of exposure to atomic bomb radiation on noncancer disease and external cause mortality among individuals exposed in utero was mediated through small head size, low birth weight, and parental loss.

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies.

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.

Radiation Risks for the Incidence of Kidney, Bladder and Other Urinary Tract Cancers: 1958-2009.

As part of the recent series of articles to create a comprehensive description of the radiation risks of solid cancer incidence after ionizing radiation exposure, based on the atomic bomb survivors' Life Span Study (LSS), this work focuses on the risks of urinary tract cancer (UTC) and kidney cancer. Analyses covered a 52-year period of follow-up, through 2009, among 105,444 eligible survivors who were alive and cancer free in 1958. This represents an additional 11 years of follow-up since the last comprehensive report, with a total of 3,079,502 person-years. We observed 790 UTC and 218 kidney cancer cases. Adjusted for smoking, there was a strong linear radiation dose response for UTC. The sex-averaged excess relative risk per 1 Gy (ERR/Gy) was 1.4 (95% confidence interval, CI: 0.82 to 2.1). Both males and females showed significantly increased ERRs/Gy with female point estimates at a factor of 3.4 (95% CI: 1.4 to 8.6) greater than male estimates. UTC radiation risks were largely unmodified by age at exposure or attained age. The attributable fraction of UTC to radiation exposure was approximately 18% while that attributed to smoking was 48%. Kidney cancer showed an increased ERR due to smoking (0.56 per 50 pack-years; 95% CI -0.007 to 1.6; P = 0.054), but we did not observe any strong associations of kidney cancer with radiation exposure, although sex-specific dose responses were found to be statistically different.

Risk of Prostate Cancer Incidence among Atomic Bomb Survivors: 1958-2009.

Epidemiological evidence for a radiation effect on prostate cancer risk has been inconsistent and largely indicative of no or little effect. Here we studied prostate cancer incidence among males of the Life Span Study cohort of atomic bomb survivors in a follow-up from 1958 to 2009, eleven years more than was previously reported. During this period there were 851 incident cases of prostate cancer among 41,544 male subjects, doubling the total number of cases in the cohort. More than 50% of the cases were diagnosed among those who were less than 20 years of age at the time of the bombings and who were at, or near, the ages of heightened prostate cancer risks during the last decade of follow-up. In analyses of the radiation dose response using Poisson regression methods, we used a baseline-rate model that allowed for calendar period effects corresponding to the emergence of prostate-specific antigen screening in the general population as well as effects of attained age and birth cohort. The model also allowed for markedly increased baseline rates among the Adult Health Study participants between 2005 and 2009, a period during which a prostate-specific antigen test was included in Adult Health Study biennial health examinations. We found a significant linear dose response with an estimated excess relative risk (ERR) per Gy of 0.57 (95% CI: 0.21, 1.00, P = 0.001). An estimated 40 of the observed cases were attributed to radiation exposure from the bombings. There was a suggestion of the ERR decreasing with increasing age at exposure (P = 0.09). We found no indication of effects of smoking, alcohol consumption and body mass index on the baseline risk of prostate cancer. The observed dose response strengthens the evidence of a radiation effect on the risk of prostate cancer incidence in the atomic bomb survivors.

Radiation Risk of Ovarian Cancer in Atomic Bomb Survivors: 1958-2009.

There is limited evidence concerning the association between radiation exposure and ovarian cancer. We evaluated radiation risk of ovarian cancer between 1958 and 2009 among 62,534 female atomic bomb survivors in the Life Span Study cohort, adding 11 years of follow-up from the previously reported study. Poisson regression methods were used to estimate excess relative risk per Gy (ERR/Gy) for total ovarian cancer and according to tumor type. We assessed the modifying effect of follow-up period and other factors on the radiation risk. We ascertained 288 first primary ovarian cancers including 77 type 1 epithelial cancers, 75 type 2 epithelial cancers, 66 epithelial cancers of undetermined type and 70 other cancers. Radiation dose was positively, although not significantly, associated with risk of total ovarian cancer [ERR/Gy = 0.30, 95% confidence interval (CI): -0.22 to 1.11]. There was a suggestion of heterogeneity in radiation effects (P = 0.08) for type 1 (ERR/Gy = -0.32, 95% CI: <-0.32 to 0.88) and type 2 cancers (ERR/Gy = 1.24, 95% CI: -0.08 to 4.16). There were no significant trends in the ERR with time since exposure or age at exposure. Further follow-up will help characterize more accurately the patterns of radiation risk for total ovarian cancer and its types.

Smoking and colorectal cancer: A pooled analysis of 10 population-based cohort studies in Japan.

Smoking has been consistently associated with the risk of colorectal cancer (CRC) in Western populations; however, evidence is limited and inconsistent in Asian people. To assess the association of smoking status, smoking intensity and smoking cessation with colorectal risk in the Japanese population, we performed a pooled analysis of 10 population-based cohort studies. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox's proportional hazards model and then pooled using a random-effects model. Among 363 409 participants followed up for 2 666 004 person-years, 9232 incident CRCs were identified. In men, compared with never smokers, ever smokers showed higher risk of CRC. The HRs (95% CI) were 1.19 (1.10-1.29) for CRC, 1.19 (1.09-1.30) for colon cancer, 1.28 (1.13-1.46) for distal colon cancer and 1.21 (1.07-1.36) for rectal cancer. Smoking was associated with risk of CRC in a dose-response manner. In women, compared with never smokers, ever smokers showed increased risk of distal colon cancer (1.47 [1.19-1.82]). There was no evidence of a significant gender difference in the association of smoking and CRC risk. Our results confirm that smoking is associated with an increased risk of CRC, both overall and subsites, in Japanese men and distal colon cancer in Japanese women.

Causal mediation analysis in nested case-control studies using conditional logistic regression.

The paper proposes an approach to causal mediation analysis in nested case-control study designs, often incorporated with countermatching schemes using conditional likelihood, and we compare the method's performance to that of mediation analysis using the Cox model for the full cohort with a continuous or dichotomous mediator. Simulation studies are conducted to assess our proposed method and investigate the efficiency relative to the cohort. We illustrate the method using actual data from two studies of potential mediation of radiation risk conducted within the Adult Health Study cohort of atomic-bomb survivors. The performance becomes comparable to that based on the full cohort, illustrating the potential for valid mediation analysis based on the reduced data obtained through the nested case-control design.

Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958-2009.

Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: - 0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose-response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (P = 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (P = 0.002). More than 60 years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958-2009.

Radiation effects on colorectal cancer rates, adjusted for smoking, alcohol intake and frequency of meat consumption and body mass index (BMI) by anatomical subsite (proximal colon, distal colon and rectum) were examined in a cohort of 105,444 atomic bomb survivors. Poisson regression methods were used to describe radiation-associated excess relative risks (ERR) and excess absolute rates (EAR) for the 1958-2009 period. There were 2,960 first primary colorectal cancers including 894 proximal, 871 distal and 1,046 rectal cancers. Smoking, alcohol intake and BMI were associated with subsite-specific cancer background rates. Significant linear dose-responses were found for total colon (sex-averaged ERR/Gy for 70 years old exposed at age 30 = 0.63, 95% confidence interval [CI]: 0.34; 0.98), proximal [ERR = 0.80, 95% CI: 0.32; 1.44] and distal colon cancers [ERR = 0.50, 95% CI: 0.04; 0.97], but not for rectal cancer [ERR = 0.023, 95% CI: -0.081; 0.13]. The ERRs for proximal and distal colon cancers were not significantly different (p = 0.41). The ERR decreased with attained age for total colon, but not for proximal colon cancer, and with calendar year for distal colon cancer. The ERRs and EARs did not vary by age at exposure, except for decreasing trend in EAR for proximal colon cancer. In conclusion, ionizing radiation is associated with increased risk of proximal and distal colon cancers. The ERR for proximal cancer persists over time, but that for distal colon cancer decreases. There continues to be no indication of radiation effects on rectal cancer incidence in this population.