An increased incidence of Hodgkin's lymphoma in patients with adult-onset sarcoma

Megan E Downing,Mandy L Ballinger,Gillian S Dite,The International Sarcoma Kindred Study Consortium

doi:10.1186/2045-3329-2-1

Abstract

BackgroundSarcomas are rare, often fatal malignancies of connective tissues that can occur in genetic predisposition syndromes or result from carcinogen exposure. Hodgkin's lymphoma (HL) is not known to contribute to any recognised familial cancer syndrome comprising sarcomas, but is known to be associated with a variety of second cancers, including sarcomas. This study describes the prevalence of HL in families affected by sarcoma.MethodsThe International Sarcoma Kindred Study (ISKS) is a prospective cohort of 561 families ascertained via a proband with adult-onset sarcoma. Cancer-specific standardised incidence ratios (SIR) for multiple primary malignancies in probands were estimated. Clinical characteristics of individuals reporting both sarcoma and HL were described. Standardised incidence ratios for the occurrence of cancer in ISKS families were also estimated.ResultsMultiple primary cancers were reported in 16% of probands, significantly higher than in the general population. The risk of HL in probands was increased 15.8-fold (95%CI 7.9-31.6) and increased risks were also seen for breast cancer (SIR 2.9, 95%CI 1.9-4.4) and thyroid cancer (SIR 8.4, 95%CI 4.2-16.8). In 8 probands with both HL and sarcoma, the diagnosis of HL preceded that of sarcoma in 7 cases, and occurred synchronously in one case. Only 3 cases of sarcoma occurred in or close to prior radiotherapy fields. The overall incidence of HL in the ISKS cohort was not significantly increased by comparison with age- and gender-specific population estimates (SIR 1.63, 95%CI 1.05-2.43), suggesting that the association between HL and sarcomas did not extend to other family members. The age of onset of non-sarcoma, non-HL cancers in families affected by both HL and sarcoma was younger than the general population (56.2 y vs 65.6 y, P < 0.0001).ConclusionsThe basis for the association between HL and sarcomas may include the carcinogenic effects of therapy combined with excellent survival rates for HL. Common risk factors for both may also exist, including both environmental and heritable factors.

Highlights

Sarcomas are rare, often fatal malignancies of connective tissues that can occur in genetic predisposition syndromes or result from carcinogen exposure
There was an increased risk of cancer other than sarcoma in International Sarcoma Kindred Study (ISKS) probands and the cumulative risk is shown in Figure 1, reinforcing the impression that sarcoma is associated with an increased incidence of other primary malignancies
Given the increased risk of Hodgkin’s lymphoma (HL) in probands with sarcoma, we focused on families affected by HL in more detail

Summary

Introduction

Often fatal malignancies of connective tissues that can occur in genetic predisposition syndromes or result from carcinogen exposure. Individual and familial germline characteristics interact with the environment to modify the risk of subsequent somatic genetic changes within cells, the accumulation of which eventually results in cancer development. Cancers often cluster in families, and while some of this clustering may arise from the common environment shared by families, a significant fraction of cancer risk is Sarcomas are rare, often fatal malignancies of connective tissues whose age of onset is typically younger than most cancers. Early age of onset of cancer increases the likelihood genetic factors are present. Sarcomas occur more commonly in a number of recognised hereditary cancer syndromes including Li-Fraumeni syndrome, retinoblastoma, neurofibromatosis type 1, Gardner’s and Werner syndromes [5]. The rarity and heterogeneity of sarcomas has presented a barrier to aetiologic study [7]

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