John D. Boice

Vanderbilt University Medical Center

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Michael T. Mumma

International Epidemiology Institute

Marilyn Stovall

The University of Texas MD Anderson Cancer Center

Sarah S. Cohen

BioStrategies (United States)

Jørgen H. Olsen

Center for Astrophysics Harvard & Smithsonian

Lawrence T. Dauer

Memorial Sloan Kettering Cancer Center

Roy E. Shore

New York University

Charles F. Lynch

University of Iowa

Jonine L. Bernstein

Memorial Sloan Kettering Cancer Center

Ashley P. Golden

Oak Ridge Associated Universities

Elizabeth D. Ellis

Oak Ridge Associated Universities

Cooperative Institutions

National Cancer Institute

348

National Institutes of Health

189

National Cancer Institute

187

New York University Press

143

Memorial Sloan Kettering Cancer Center

108

Division of Cancer Epidemiology and Genetics

Danish Cancer Society

Fred Hutch Cancer Center

Karolinska Institutet

Harvard University

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Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy

JNCI Journal of the National Cancer Institute (2012)

Lois B. Travis Andrea K. Ng James M. Allan Ching‐Hon Pui Ann R. Kennedy

Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.

Malignant disease

10.1093/jnci/djr533

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Citations (213)

Radiation-Induced Skin Carcinomas of the Head and Neck

Radiation Research (1991)

Elaine Ron Baruch Modan Dale L. Preston Esther Alfandary Marilyn Stovall

Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City (Shore et al., Radiat. Res. 100, 192-204, 1984). This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy.

Tinea Capitis

10.2307/3578117

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Citations (168)

Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors

Acta Oncologica (2013)

Laura Madanat‐Harjuoja Päivi M. Lähteenmäki Tadeusz Dyba Mika Gissler John D. Boice

Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own.We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers.The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children.Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.

10.3109/0284186x.2012.758870

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Breast Cancer Following Radiotherapy and Chemotherapy Among Young Women With Hodgkin Disease

JAMA (2003)

Lois B. Travis Deirdre A. Hill Graça M. Dores Mary Gospodarowicz Flora E. van Leeuwen

Context

Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.

Objective

To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.

Design, Setting, and Subjects

Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.

Main Outcome Measures

Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.

Results

Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5;P= .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P= .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.

Conclusions

Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.

10.1001/jama.290.4.465

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Citations (643)

Cancer risk among chernobyl cleanup workers in Estonia and Latvia, 1986–1998

International Journal of Cancer (2006)

Mati Rahu Mati Rahu Anssi Auvinen Mare Tekkel Aivars Stengrēvics

Two cohorts of Chernobyl cleanup workers from Estonia (4,786 men) and Latvia (5,546 men) were followed from 1986 to 1998 to investigate cancer incidence among persons exposed to ionizing radiation from the Chernobyl accident. Each cohort was identified from various independent sources and followed using nationwide population and mortality registries. Cancers were ascertained by linkage with nationwide cancer registries. Overall, 75 incident cancers were identified in the Estonian cohort and 80 in the Latvian cohort. The combined-cohort standardized incidence ratio (SIR) for all cancers was 1.15 (95% confidence interval (CI) = 0.98-1.34) and for leukemia, 1.53 (95% CI = 0.62-3.17; n = 7). Statistically significant excess cases of thyroid (SIR = 7.06, 95% CI = 2.84-14.55; n = 7) and brain cancer (SIR = 2.14, 95% CI = 1.07-3.83; n = 11) were found, mainly based on Latvian data. However, there was no evidence of a dose response for any of these sites, and the relationship to radiation exposure remains to be established. Excess of thyroid cancer cases observed may have been due to screening, the leukemia cases included 2 unconfirmed diagnoses, and the excess cases of brain tumors may have been a chance finding. There was an indication of increased risk associated with early entry to the Chernobyl area and late follow-up, though not statistically significant. Further follow-up of Chernobyl cleanup workers is warranted to clarify the possible health effects of radiation exposure.

Chernobyl Nuclear Accident

Standardized mortality ratio

Latvian

10.1002/ijc.21733

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Citations (48)

Radiation Studies of Women Treated for Benign Gynecologic Disease

JNCI Journal of the National Cancer Institute (1986)

John D. Boice Ruth A. Kleinerman

Radiation Studies of Women Treated for Benign Gynecologic Disease Get access John D. Boice, Jr, Sc.D., John D. Boice, Jr, Sc.D. Radiation Epidemiology Branch, Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Maryland 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth A. Kleinerman, M.P.H. Ruth A. Kleinerman, M.P.H. Radiation Epidemiology Branch, Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Maryland 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 3, March 1986, Pages 4549, https://doi.org/10.1093/jnci/76.3.549 Published: 01 March 1986

Biostatistics

Human services

10.1093/jnci/76.3.549

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A million persons, a million dreams: a vision for a national center of radiation epidemiology and biology

International Journal of Radiation Biology (2021)

John D. Boice Brian Quinn Isaf Al‐Nabulsi Armin Ansari Paul K. Blake

Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal.

Center (category theory)

10.1080/09553002.2021.1988183

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Citations (37)

Reply to Comment on ‘Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection’

Journal of Radiological Protection (2019)

Roy E. Shore Harold L. Beck John D. Boice Emily Caffrey S. Scott Davis

10.1088/1361-6498/ab077f

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Citations (3)

Genetic Disease in the Children of Danish Survivors of Childhood and Adolescent Cancer

Journal of Clinical Oncology (2011)

Jeanette Falck Winther Jørgen H. Olsen Huiyun Wu Yu Shyr John J. Mulvihill

Purpose Preconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes. Patients and Methods A case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model. Results No statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P = .94). A statistically significant association between abdomino-pelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P = .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56). Conclusion Mutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes.

10.1200/jco.2011.35.0504

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Citations (103)

Risks of Leukemia in Japanese Atomic Bomb Survivors, in Women Treated for Cervical Cancer, and in Patients Treated for Ankylosing Spondylitis

Radiation Research (1999)

Mark P. Little Helen A. Weiss John D. Boice Sarah C. Darby Nicholas Day

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.

Acute lymphocytic leukemia

10.2307/3580328

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Citations (91)