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Second Primary Cancers in Thyroid Cancer Patients: A Multinational Record Linkage Study

Metabolic Unit (T.C.S., M.W.J.S., R.M.R.), Western General Hospital, Edinburgh EH4 2XU, United Kingdom; Scottish Cancer Registry (D.H.B.), Edinburgh EH12 9EB, United Kingdom; International Agency for Research on Cancer (G.S., P.Bo., P.Br.), 69372 Lyon, France; Finnish Cancer Registry (E.P.), Institute for Statistical and Epidemiological Cancer Research, FIN-00170 Helsinki, Finland; Division of Molecular Genetic Epidemiology (K.H.), German Cancer Research Center, 69120 Heidelberg, Germany; Department of Biosciences at Novum (K.H.), Karolinska Institute, SE-171 77 Hudinge, Sweden; Institute of Population-Based Cancer Research (A.A.), 0310 Oslo, Norway; Central Cancer Registry (E.T.), Woolloomooloo, New South Wales 2011, Australia; Institute of Cancer Epidemiology (S.F.), Danish Cancer Society, DK-2100 Copenhagen, Denmark; Cancer Control Research Programme (M.L.M.), British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6; Center for Molecular Epidemiology (C.K.-S.), Singapore 6874 4971; Cancer Registry of Slovenia (V.P.-K.), Institute of Oncology, Ljubljana, Slovenia SI-1000; Epidemiology and Cancer Registry (E.V.K.), CancerCare Manitoba, Winnipeg, Canada R3E 0V9; Community Health Sciences (E.V.K.), University of Manitoba, Winnipeg, Canada R3T 2N2; School of Public Health (E.V.K.), University of Sydney, Sydney 2006, Australia; Program Evaluation and Surveillance (J.M.T.), Saskatchewan Cancer Agency, Regina, Saskatchewan, Canada S7N 4H4; Icelandic Cancer Registry (J.G.J.), Icelandic Cancer Society, IS-125 Reykjavik, Iceland; The Medical Faculty (J.G.J.), University of Iceland, 101 Reykjavik, Iceland; and Cancer Registry of Zaragoza (C.M.), Health Department of Aragon Government, 50004 Zaragoza, Spain

Address all correspondence and requests for reprints to: Dr. Mark W. J. Strachan, Metabolic Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. E-mail: mark.strachan{at}luht.scot.nhs.uk.

Context: Increasing incidence and improved prognosis of thyroid cancer have led to concern about the development of second primary cancers, especially after radioiodine treatment. Thyroid cancer can also arise as a second primary neoplasm after other cancers.

Objective: The objective of the study was to assess the risk of second primary cancer after thyroid cancer and vice versa.

Design: This was a multinational record linkage study.

Setting: The study was conducted at 13 population-based cancer registries in Europe, Canada, Australia, and Singapore.

Patients or Other Participants: A cohort of 39,002 people (356,035 person-yr of follow-up) with primary thyroid cancer were followed up for SPN for up to 25 yr, and 1,990 cases of thyroid cancer were diagnosed after another primary cancer.

Main Outcome Measures: To assess any possible excess of second primary neoplasms after thyroid cancer, the observed numbers of neoplasms were compared with expected numbers derived from age-, sex-, and calendar period-specific cancer incidence rates from each of the cancer registries, yielding standardized incidence ratios (SIRs). The SIR of second primary thyroid cancer after various types of cancer was also calculated.

Results: During the observation period, there were 2821 second primary cancers (all sites combined) after initial diagnosis of thyroid cancer, SIR of 1.31 (95% confidence interval 1.26–1.36) with significantly elevated risks for many specific cancers. Significantly elevated risks of second primary thyroid cancer were also seen after many types of cancer.

Conclusion: Pooled data from 13 cancer registries show a 30% increased risk of second primary cancer after thyroid cancer and increased risks of thyroid cancer after various primary cancers. Although bias (detection, surveillance, misclassification) and chance may contribute to some of these observations, it seems likely that shared risk factors and treatment effects are implicated in many. When following up patients who have been treated for primary thyroid cancer, clinicians should maintain a high index of suspicion for second primary cancers.

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