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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

ABSTRACT: The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood 131I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.

SUBMITTER: Morton LM

PROVIDER: S-EPMC9022889 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

Morton Lindsay M LM Karyadi Danielle M DM Stewart Chip C Bogdanova Tetiana I TI Dawson Eric T ET Steinberg Mia K MK Dai Jieqiong J Hartley Stephen W SW Schonfeld Sara J SJ Sampson Joshua N JN Maruvka Yosef E YE Kapoor Vidushi V Ramsden Dale A DA Carvajal-Garcia Juan J Perou Charles M CM Parker Joel S JS Krznaric Marko M Yeager Meredith M Boland Joseph F JF Hutchinson Amy A Hicks Belynda D BD Dagnall Casey L CL Gastier-Foster Julie M JM Bowen Jay J Lee Olivia O Machiela Mitchell J MJ Cahoon Elizabeth K EK Brenner Alina V AV Mabuchi Kiyohiko K Drozdovitch Vladimir V Masiuk Sergii S Chepurny Mykola M Zurnadzhy Liudmyla Yu LY Hatch Maureen M Berrington de Gonzalez Amy A Thomas Gerry A GA Tronko Mykola D MD Getz Gad G Chanock Stephen J SJ

Science (New York, N.Y.) 20210422 6543

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (<sup>131</sup>I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood <sup>131</sup>I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitog ...[more]

PMID: 33888599

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Project description:BackgroundThe issue of whether radiation-induced thyroid cancer is pathologically different from sporadic remains not fully answered. This study compared structural characteristics and invasive features of papillary thyroid carcinoma (PTC) in two age-matched groups: patients who were children (?4 years old) at the time of the Chernobyl accident and who lived in three regions of Ukraine most contaminated by radioactive iodine 131I ("radiogenic" cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to 131I ("sporadic" cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual 131I thyroid dose.MethodsThe study included 301 radiogenic and 194 sporadic PTCs. According to age at surgery, patients were subdivided into children (?14 years old), adolescents (15-18 years old), and adults (19-28 years old). Statistical analyses included univariate tests and multivariable logistic regression within and across the age subgroups. Analyses of morphological features related to 131I doses were conducted among exposed patients on categorical and continuous scales controlling for sex and age.ResultsAmong children, radiogenic PTC displayed a significantly higher frequency of tumors with a dominant solid growth pattern, intrathyroidal spread, extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adolescents more frequently displayed extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adults more frequently had intrathyroidal spread and extrathyroidal extension. The frequency of PTC with dominant papillary pattern and oxyphilic cell metaplasia was significantly lower in radiogenic compared to sporadic tumors for all age groups. Manifestations of tumor aggressiveness were most frequent in children compared to adolescents and adults regardless of etiology.ConclusionsRadiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.

Project description:ImportanceTo our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.ObjectiveTo study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.Design, setting, and participantsThis was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.Main outcomes and measuresFor analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.ResultsOf the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.Conclusions and relevanceThis cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.

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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

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