The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation cohort of 154 patients with sporadic EC was also included. The XPD Asp312Asn (rs1799793) was found to be associated with the risk of developing second primary ESCC (P=0.015). The resultant variant was also involved in the onset of sporadic ESCC (P=0.0018). To know in advance who among long-term cancer survivors have an increased risk of EC could lead to a more appropriate follow-up strategy.
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This work was supported by the following grants: Associazione Italiana per la Ricerca sul Cancro (AIRC, Ref. 10430), Ministero della Istruzione, della Università e della Ricerca (MIUR, Prot. 2010MCLPLB-003), Veneto Institute of Oncology IOV-IRCCS 5xmille.
The authors declare no conflict of interest.
This paper is dedicated to the friendship and memory of Savina Aversa.
Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website
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Boldrin, E., Rumiato, E., Fassan, M. et al. Genetic risk of subsequent esophageal cancer in lymphoma and breast cancer long-term survival patients: a pilot study. Pharmacogenomics J 16, 266–271 (2016) doi:10.1038/tpj.2015.41
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