Radiation epidemiology and health effects following low-level radiation exposure.

Radiation epidemiology is the study of human disease following radiation exposure to populations. Epidemiologic studies of radiation-exposed populations have been conducted for nearly 100 years, starting with the radium dial painters in the 1920s and most recently with large-scale studies of radiation workers. As radiation epidemiology has become increasingly sophisticated it is used for setting radiation protection standards as well as to guide the compensation programmes in place for nuclear weapons workers, nuclear weapons test participants, and other occupationally exposed workers in the United States and elsewhere. It is known with high assurance that radiation effects at levels above 100-150 mGy can be detected as evidenced in multiple population studies conducted around the world. The challenge for radiation epidemiology is evaluating the effects at low doses, below about 100 mGy of low-linear energy transfer radiation, and assessing the risks following low dose-rate exposures over years. The weakness of radiation epidemiology in directly studying low dose and low dose-rate exposures is that the signal, i.e. the excess numbers of cancers associated with low-level radiation exposure, is so very small that it cannot be seen against the very high background occurrence of cancer in the population, i.e. a lifetime risk of incidence reaching up to about 38% (i.e. 1 in 3 persons will develop a cancer in their lifetime). Thus, extrapolation models are used for the management of risk at low doses and low dose rates, but having adequate information from low dose and low dose-rate studies would be highly desirable. An overview of recently conducted radiation epidemiologic studies which evaluate risk following low-level radiation exposures is presented. Future improvements in risk assessment for radiation protection may come from increasingly informative epidemiologic studies, combined with mechanistic radiobiologic understanding of adverse outcome pathways, with both incorporated into biologically based models.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

Dose-rate effects in radiation biology and radiation protection.

Quantification of biological effects (cancer, other diseases, and cell damage) associated with exposure to ionising radiation has been a major issue for the International Commission on Radiological Protection (ICRP) since its foundation in 1928. While there is a wealth of information on the effects on human health for whole-body doses above approximately 100 mGy, the effects associated with doses below 100 mGy are still being investigated and debated intensively. The current radiological protection approach, proposed by ICRP for workers and the public, is largely based on risks obtained from high-dose and high-dose-rate studies, such as the Japanese Life Span Study on atomic bomb survivors. The risk coefficients obtained from these studies can be reduced by the dose and dose-rate effectiveness factor (DDREF) to account for the assumed lower effectiveness of low-dose and low-dose-rate exposures. The 2007 ICRP Recommendations continue to propose a value of 2 for DDREF, while other international organisations suggest either application of different values or abandonment of the factor. This paper summarises the current status of discussions, and highlights issues that are relevant to reassessing the magnitude and application of DDREF.

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident.

We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10(-2) and 29.0 · 10(-2), respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.

Invited commentary: missing doses in the life span study of Japanese atomic bomb survivors.

The Life Span Study is a long-term epidemiologic cohort study of survivors of the atomic bombs dropped on Hiroshima and Nagasaki, Japan. In this issue of the Journal, Richardson et al. (Am J Epidemiol. 2013;177(6):562-568) suggest that those who died in the earliest years of follow-up were more likely to have a missing dose of radiation exposure assigned, leading to a bias in the radiation risk estimates. We show that nearly all members of the cohort had shielding information recorded before the beginning of follow-up and that much of the alleged bias that Richardson et al. describe simply reflects the geographic distribution of shielding conditions for which reliable dosimetry was impossible.

ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

BACKGROUND: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful. METHODS: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay. RESULTS: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio. CONCLUSION: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure.

Dosimetry for a study of low-dose radiation cataracts among Chernobyl clean-up workers.

A cohort of 8,607 Ukrainian Chernobyl clean-up workers during 1986-1987 was formed to study cataract formation after ionizing radiation exposure. Study eligibility required the availability of sufficient exposure information to permit the reconstruction of doses to the lens of the eye. Eligible groups included civilian workers, such as those who built the "sarcophagus" over the reactor, Chernobyl Nuclear Power Plant Workers, and military reservists who were conscripted for clean-up work. Many of the official doses for workers were estimates, because only a minority wore radiation badges. For 106 military workers, electron paramagnetic resonance (EPR) measurements of extracted teeth were compared with the recorded doses as the basis to adjust the recorded gamma-ray doses and provide estimates of uncertainties. Beta-particle doses to the lens were estimated with an algorithm devised to take into account the nature and location of Chernobyl work, time since the accident, and protective measures taken. A Monte Carlo routine generated 500 random estimates for each individual from the uncertainty distributions of the gamma-ray dose and of the ratio of beta-particle to gamma-ray doses. The geometric mean of the 500 combined beta-particle and gamma-ray dose estimates for each individual was used in the data analyses. The median estimated lens dose for the cohort was 123 mGy, while 4.4% received >500 mGy.

Cataracts among Chernobyl clean-up workers: implications regarding permissible eye exposures.

The eyes of a prospective cohort of 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. The prevalence of strictly age-related cataracts was low, as expected (only 3.9% had nuclear cataracts at either examination), since 90% of the cohort was younger than 55 years of age at first examination. However, posterior subcapsular or cortical cataracts characteristic of radiation exposure were present in 25% of the subjects. The data for Stage 1 cataracts, and specifically for posterior subcapsular cataracts, revealed a significant dose response. When various cataract end points were analyzed for dose thresholds, the confidence intervals all excluded values greater than 700 mGy. Linear-quadratic dose-response models yielded mostly linear associations, with weak evidence of upward curvature. The findings do not support the ICRP 60 risk guideline assumption of a 5-Gy threshold for "detectable opacities" from protracted exposures but rather point to a dose-effect threshold of under 1 Gy. Thus, given that cataract is the dose-limiting ocular pathology in current eye risk guidelines, revision of the allowable exposure of the human visual system to ionizing radiation should be considered.

Circulating enterolactone and risk of breast cancer: a prospective study in New York.

It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study.

We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aspirin and lung cancer in women.

The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type.

Handheld cellular telephones and risk of acoustic neuroma.

The hypothesis that intracranial energy deposition from handheld cellular telephones causes acoustic neuroma was tested in an epidemiologic study of 90 patients and 86 control subjects. The relative risk was 0.9 (p = 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. Further efforts should focus on potentially longer induction periods.