Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects

Ethel S Gilbert; Rochelle E Curtis; Michael Hauptmann; Ruth A Kleinerman; Charles F Lynch; Marilyn Stovall; Susan A Smith; Rita Weathers; Michael Andersson; Graça M Dores; Joseph F Fraumeni Jr; Sophie D Fossa; Per Hall; David C Hodgson; Eric J Holowaty; Heikki Joensuu; Tom B Johannesen; Froydis Langmark; Magnus Kaijser; Eero Pukkala; Preetha Rajaraman; Hans H Storm; Leila Vaalavirta; Alexandra W van den Belt-Dusebout; Berthe M Aleman; Lois B Travis; Lindsay M Morton; Flora E van Leeuwen

doi:10.1667/RR14453.1

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Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects

Journal article

Peer reviewed

Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects

Ethel S Gilbert, Rochelle E Curtis, Michael Hauptmann, Ruth A Kleinerman, Charles F Lynch, Marilyn Stovall, Susan A Smith, Rita Weathers, Michael Andersson, Graça M Dores, …

Radiation research, Vol.187(2), pp.186-195

02/2017

DOI: 10.1667/RR14453.1

PMCID: PMC5410713

PMID: 28118119

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http://doi.org/10.1667/RR14453.1View

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Abstract

To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls. Among 327 cases and 678 controls, mean doses to the stomach were 15.3 Gy, 24.7 Gy and 1.9 Gy, respectively, for Hodgkin lymphoma, testicular cancer and cervical cancer survivors, with an overall mean dose of 10.3 Gy. Risk increased with increasing radiation dose to the stomach cancer site (P < 0.001) with no evidence of nonlinearity or of a downturn at the highest doses (≥35 Gy). The pooled excess odds ratio per Gy (EOR/Gy) was 0.091 [95% confidence interval (CI): 0.036-0.20] with estimates of 0.049 (95% CI: 0.007-0.16) for Hodgkin lymphoma, 0.27 (95% CI: 0.054-1.44) for testicular cancer and 0.096 (95% CI: -0.002-0.39) for cervical cancer (P homogeneity = 0.25). The EOR/Gy increased with time since exposure (P trend = 0.004), with an EOR/Gy of 0.38 (95% CI: 0.12-1.04) for stomach cancer occurring ≥20 years postirradiation corresponding to odds ratios of 4.8 and 10.5 at radiation doses to the stomach of 10 and 25 Gy, respectively. Of 111 stomach cancers occurring ≥20 years after radiotherapy, 63.8 (57%) could be attributed to radiotherapy. Our findings differ from those based on Japanese atomic-bomb survivors, where the overall EOR/Gy was higher and where there was no evidence of an increase with time since exposure. By pooling data from three studies, we demonstrated a clear increase in stomach cancer risk over a wide range of doses from fractionated radiotherapy with the highest risks occurring many years after exposure. These findings highlight the need to directly evaluate the health effects of high-dose fractionated radiotherapy rather than relying on the data of persons exposed at low and moderate acute doses.

Uterine Cervical Neoplasms - radiotherapy

Humans

Middle Aged

Neoplasms, Radiation-Induced - etiology

Male

Hodgkin Disease - radiotherapy

Internationality

Testicular Neoplasms - radiotherapy

Adolescent

Aged, 80 and over

Adult

Dose Fractionation

Female

Stomach Neoplasms - epidemiology

Aged

Neoplasms, Radiation-Induced - epidemiology

Stomach Neoplasms - etiology

Child

Dose-Response Relationship, Radiation

Details

Title: Subtitle: Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects
Creators: Ethel S Gilbert - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Rochelle E Curtis - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Michael Hauptmann - b Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Ruth A Kleinerman - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Charles F Lynch - c Department of Epidemiology, University of Iowa, Iowa City, Iowa
Marilyn Stovall - d Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas
Susan A Smith - d Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas
Rita Weathers - d Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas
Michael Andersson - e Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark
Graça M Dores - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Joseph F Fraumeni Jr - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Sophie D Fossa - f Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway
Per Hall - g Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden
David C Hodgson - h Department of Radiation Oncology, University of Toronto, Toronto, Canada
Eric J Holowaty - i Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
Heikki Joensuu - j Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
Tom B Johannesen - k Cancer Registry of Norway, Oslo, Norway
Froydis Langmark - k Cancer Registry of Norway, Oslo, Norway
Magnus Kaijser - l Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
Eero Pukkala - n School of Health Sciences, University of Tampere, Tampere, Finland
Preetha Rajaraman - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Hans H Storm - Danish Cancer Society, Copenhagen, Denmark
Leila Vaalavirta - j Department of Oncology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
Alexandra W van den Belt-Dusebout - b Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Berthe M Aleman - p Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and
Lois B Travis - q Melvin and Bren Simon Cancer Center, Indianapolis University School of Medicine, Indianapolis, Indiana
Lindsay M Morton - a Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland
Flora E van Leeuwen - b Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Resource Type: Journal article
Publication Details: Radiation research, Vol.187(2), pp.186-195
DOI: 10.1667/RR14453.1
PMID: 28118119
PMCID: PMC5410713
NLM abbreviation: Radiat Res
ISSN: 0033-7587
eISSN: 1938-5404
Publisher: United States
Grant note: N02CP31003 / NCI NIH HHS N02CP31136 / NCI NIH HHS N01CP31154 / NCI NIH HHS N01CP31156 / NIAID NIH HHS Z99 CA999999 / Intramural NIH HHS N01CP31019 / NCI NIH HHS N02CP55503 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 02/2017
Academic Unit: Epidemiology
Record Identifier: 9983996097802771

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