Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors

Abstract

Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. The occurrence of second malignant neoplasms (SMN) is influenced by a myriad of factors, including the late effects of cancer therapy, shared aetiological factors with the primary cancer (such as tobacco use, excessive alcohol intake, and obesity), genetic predisposition, environmental determinants, host effects, and combinations of factors, including gene–environment interactions. The influence of these factors on SMN in survivors of adult-onset cancer is reviewed here. We also discuss how modifiable behavioural and lifestyle factors may contribute to SMN, and how these factors can be managed. Cancer survivorship provides an opportune time for oncologists and other health-care providers to counsel patients with regard to health promotion, not only to reduce SMN risk, but to minimize co-morbidities. In particular, the importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors. Clinicians can also play a critical role by endorsing genetic counselling for selected patients and making referrals to dieticians, exercise trainers, and others to assist with lifestyle change interventions.

Key Points

  • Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA

  • Second malignant neoplasms (SMN) reflect the role of many factors, including the late effects of therapy, shared aetiological factors, genetic predisposition, environmental determinants, host effects, and combinations of influences

  • Cancer survivorship provides an opportune time for oncologists and other healthcare providers to counsel patients with regard to health promotion to reduce SMN risk

  • The importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors

  • Clinicians can play a critical role by endorsing genetic counselling for selected patients and making referrals to dieticians, exercise trainers, and others to assist with lifestyle change interventions

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Schematic illustration of risk factors for second malignant neoplasms.

References

  1. National Cancer Institute. SEER Cancer Statistics Review, 1975–2007 [online], (2010).

  2. National Cancer Institute. Provocative questions: identifying problems to drive progress against cancer [online], (2012).

  3. Siegel, R. et al. Cancer treatment and survivorship statistics. CA Cancer J. Clin. 62, 220–241 (2012).

    Article  PubMed  Google Scholar 

  4. [No authors listed]. Cancer survivors: living longer, and now, better. Lancet 364, 2153–2154 (2004).

  5. Travis, L. B. Therapy-associated solid tumors. Acta Oncol. 41, 323–333 (2002).

    Article  PubMed  Google Scholar 

  6. Curtis, R. E., Ron, E., Hankey, B. F. & Hoover, R. N. in New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973–2000 (eds Curtis, R. E. et al.) NIH Publ. No. 05–0532, 181–206 (National Cancer Institute, 2006).

    Google Scholar 

  7. Ng, A. K. et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger. J. Clin. Oncol. 20, 2101–2108 (2002).

    Article  PubMed  Google Scholar 

  8. Travis, L. B. et al. Cancer survivorship--genetic susceptibility and second primary cancers: research strategies and recommendations. J. Natl Cancer Inst. 98, 15–25 (2006).

    Article  PubMed  Google Scholar 

  9. Travis, L. B., Bhatia, S., Allan, J. M., Oeffinger, K. C. & Ng, A. in Cancer: Principles and Practice of Oncology, 9th edn (eds Devita, V. T., Lawrence, T. S. & Rosenberg, S. A.) 2393–2410 (Lippincott Williams and Wilkins, 2011).

    Google Scholar 

  10. Dores, G. M. et al. Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J. Clin. Oncol. 20, 3484–3494 (2002).

    Article  PubMed  Google Scholar 

  11. Franklin, J. et al. Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials. Ann. Oncol. 17, 1749–1760 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Omer, B. et al. Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults. Br. J. Haematol. 158, 615–625 (2012).

    Article  PubMed  Google Scholar 

  13. Hodgson, D. C. et al. Long-term solid cancer risk among 5-year survivors of Hodgkin's lymphoma. J. Clin. Oncol. 25, 1489–1497 (2007).

    Article  PubMed  Google Scholar 

  14. Hemminki, K., Liu, H. & Sundquist, J. Second cancers after testicular cancer diagnosed after in Sweden. Ann. Oncol. 21, 1546–1551 (2010) (1980).

    Article  CAS  PubMed  Google Scholar 

  15. Travis, L. B. et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J. Natl Cancer Inst. 97, 1354–1365 (2005).

    Article  PubMed  Google Scholar 

  16. van den Belt-Dusebout, A. W. et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J. Clin. Oncol. 25, 4370–4378 (2007).

    Article  PubMed  Google Scholar 

  17. Travis, L. B. et al. Second malignant neoplasms and cardiovascular disease following radiotherapy. J. Natl Cancer Inst. 104, 357–370 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. National Council on Radiation Protection and Measurements. Report No. 170: Second Primary Cancers and Cardiovascular Disease After Radiotherapy [online], (2012).

  19. Chaturvedi, A. K. et al. Second cancers among 104, 760 survivors of cervical cancer: evaluation of long-term risk. J. Natl Cancer Inst. 99, 1634–1643 (2007).

    Article  PubMed  Google Scholar 

  20. Bhojani, N. et al. The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population-based study on 17,845 patients. Int. J. Radiat. Oncol. Biol. Phys. 76, 342–348 (2010).

    Article  PubMed  Google Scholar 

  21. Rapiti, E. et al. Increased risk of colon cancer after external radiation therapy for prostate cancer. Int. J. Cancer 123, 1141–1145 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Kirova, Y. M., Vilcoq, J. R., Asselain, B., Sastre-Garau, X. & Fourquet, A. Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review. Cancer 104, 856–863 (2005).

    Article  PubMed  Google Scholar 

  23. Nakamura, R. et al. Angiosarcoma arising in the breast following breast-conserving surgery with radiation for breast carcinoma. Breast Cancer 14, 245–249 (2007).

    Article  PubMed  Google Scholar 

  24. Rubino, C. et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res. Treat. 89, 277–288 (2005).

    Article  PubMed  Google Scholar 

  25. Kaufman, E. L., Jacobson, J. S., Hershman, D. L., Desai, M. & Neugut, A. I. Effect of breast cancer radiotherapy and cigarette smoking on risk of second primary lung cancer. J. Clin. Oncol. 26, 392–398 (2008).

    Article  PubMed  Google Scholar 

  26. Neugut, A. I. et al. Lung cancer after radiation therapy for breast cancer. Cancer 71, 3054–3057 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Zablotska, L. B., Chak, A., Das, A. & Neugut, A. I. Increased risk of squamous cell esophageal cancer after adjuvant radiation therapy for primary breast cancer. Am. J. Epidemiol. 161, 330–337 (2005).

    Article  PubMed  Google Scholar 

  28. Boice, J. D. Jr, Harvey, E. B., Blettner, M., Stovall, M. & Flannery, J. T. Cancer in the contralateral breast after radiotherapy for breast cancer. N. Engl. J. Med. 326, 781–785 (1992).

    Article  PubMed  Google Scholar 

  29. Hooning, M. J. et al. Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer. J. Clin. Oncol. 26, 5561–5568 (2008).

    Article  PubMed  Google Scholar 

  30. Stovall, M. et al. Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the WECARE study. Int. J. Radiat. Oncol. Biol. Phys. 72, 1021–1030 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Berrington de Gonzalez, A. et al. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol. 12, 353–360 (2011).

    Article  PubMed  Google Scholar 

  32. Engert, A. et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N. Engl. J. Med. 363, 640–652 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Girinsky, T. et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother. Oncol. 79, 270–277 (2006).

    Article  PubMed  Google Scholar 

  34. Harris, J. R. & Hellman, S. Put the “hockey stick” on ice. Int. J. Radiat. Oncol. Biol. Phys. 15, 497–499 (1988).

    Article  CAS  PubMed  Google Scholar 

  35. Classen, J. et al. Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial. J. Clin. Oncol. 21, 1101–1106 (2003).

    Article  PubMed  Google Scholar 

  36. Classen, J. et al. Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG). Br. J. Cancer 90, 2305–2311 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wong, F. L. et al. Cancer incidence after retinoblastoma. radiation dose and sarcoma risk. JAMA 278, 1262–1267 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Kuttesch, J. F. Jr et al. Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas. J. Clin. Oncol. 14, 2818–2825 (1996).

    Article  PubMed  Google Scholar 

  39. Travis, L. B. et al. Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290, 465–475 (2003).

    Article  PubMed  Google Scholar 

  40. Travis, L. B. et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J. Natl Cancer Inst. 94, 182–192 (2002).

    Article  PubMed  Google Scholar 

  41. van den Belt-Dusebout, A. W. et al. Roles of radiation dose and chemotherapy in the etiology of stomach cancer as a second malignancy. Int. J. Radiat. Oncol. Biol. Phys. 75, 1420–1429 (2009).

    Article  PubMed  Google Scholar 

  42. Neglia, J. P. et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J. Natl Cancer Inst. 98, 1528–1537 (2006).

    Article  PubMed  Google Scholar 

  43. Bhatti, P. et al. Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the Childhood Cancer Survivor Study. Radiat. Res. 174, 741–752 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sigurdson, A. J. et al. Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet 365, 2014–2023 (2005).

    Article  PubMed  Google Scholar 

  45. De Bruin, M. L. et al. Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes. J. Clin. Oncol. 27, 4239–4246 (2009).

    Article  PubMed  Google Scholar 

  46. Ng, A. K. et al. Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood 100, 1989–1996 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Kry, S. F. et al. The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 62, 1195–1203 (2005).

    Article  PubMed  Google Scholar 

  48. Purdy, J. A. Dose to normal tissues outside the radiation therapy patient's treated volume: a review of different radiation therapy techniques. Health Phys. 95, 666–676 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Brodin, N. P. et al. Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma. Acta Oncol. 50, 806–816 (2011).

    Article  PubMed  Google Scholar 

  50. Bednarz, B., Athar, B. & Xu, X. G. A comparative study on the risk of second primary cancers in out-of-field organs associated with radiotherapy of localized prostate carcinoma using Monte Carlo-based accelerator and patient models. Medical Phys. 37, 1987–1994 (2010).

    Article  Google Scholar 

  51. Zwahlen, D. R. et al. Effect of intensity-modulated pelvic radiotherapy on second cancer risk in the postoperative treatment of endometrial and cervical cancer. Int. J. Radiat. Oncol. Biol. Phys. 74, 539–545 (2009).

    Article  PubMed  Google Scholar 

  52. Zacharatou Jarlskog, C. & Paganetti, H. Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age. Int. J. Radiat. Oncol. Biol. Phys. 72, 228–235 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Swerdlow, S. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edn (IARC Press, 2008).

    Google Scholar 

  54. Sill, H., Olipitz, W., Zebisch, A., Schulz, E. & Wolfler, A. Therapy-related myeloid neoplasms: pathobiology and clinical characteristics. Br. J. Pharmacol. 162, 792–805 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Attal, M. et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N. Engl. J. Med. 366, 1782–1791 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. McCarthy, P. L. et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N. Engl. J. Med. 366, 1770–1781 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pedersen-Bjergaard, J., Pedersen, M., Roulston, D. & Philip, P. Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 86, 3542–3552 (1995).

    CAS  PubMed  Google Scholar 

  58. Leone, G., Pagano, L., Ben-Yehuda, D. & Voso, M. T. Therapy-related leukemia and myelodysplasia: susceptibility and incidence. Haematologica 92, 1389–1398 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Travis, L. B. et al. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N. Engl. J. Med. 340, 351–357 (1999).

    Article  CAS  PubMed  Google Scholar 

  60. Travis, L. B. et al. Treatment-associated leukemia following testicular cancer. J. Natl Cancer Inst. 92, 1165–1171 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Pedersen-Bjergaard, J. et al. Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338, 359–363 (1991).

    Article  CAS  PubMed  Google Scholar 

  62. Seedhouse, C. & Russell, N. Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia. Br. J. Haematol. 137, 513–529 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Godley, L. A. & Larson, R. A. Therapy-related myeloid leukemia. Semin. Oncol. 35, 418–429 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Leleu, X. et al. Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenstrom macroglobulinemia treated with nucleoside analogs. J. Clin. Oncol. 27, 250–255 (2009).

    Article  PubMed  Google Scholar 

  65. Morrison, V. A. et al. Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an Intergroup Study, Cancer and Leukemia Group B 9011. J. Clin. Oncol. 20, 3878–3884 (2002).

    Article  PubMed  Google Scholar 

  66. Neugut, A. I., Robinson, E., Nieves, J., Murray, T. & Tsai, W. Y. Poor survival of treatment-related acute nonlymphocytic leukemia. JAMA 264, 1006–1008 (1990).

    Article  CAS  PubMed  Google Scholar 

  67. Mauritzson, N. et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia 16, 2366–2378 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Schoch, C., Kern, W., Schnittger, S., Hiddemann, W. & Haferlach, T. Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 18, 120–125 (2004).

    Article  CAS  PubMed  Google Scholar 

  69. Lyman, G. H. & Dale, D. C. Long-term outcomes of myeloid growth factor treatment. J. Natl Compr. Canc. Netw. 9, 945–952 (2011).

    Article  CAS  PubMed  Google Scholar 

  70. Hershman, D. et al. Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J. Natl Cancer Inst. 99, 196–205 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Lyman, G. H. et al. Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review. J. Clin. Oncol. 28, 2914–2924 (2010).

    Article  PubMed  Google Scholar 

  72. Henderson, T. O. et al. Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int. J. Radiat. Oncol. Biol. Phys. 84, 224–230 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Swerdlow, A. J. et al. Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment. J. Clin. Oncol. 19, 1610–1618 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. van Leeuwen, F. E. et al. Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease. J. Natl Cancer Inst. 87, 1530–1537 (1995).

    Article  CAS  PubMed  Google Scholar 

  75. Swerdlow, A. J. et al. Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study. J. Clin. Oncol. 29, 4096–4104 (2011).

    Article  CAS  PubMed  Google Scholar 

  76. Andre, M. et al. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. Blood 103, 1222–1228 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Mudie, N. Y. et al. Risk of second malignancy after non-Hodgkin's lymphoma: a British cohort study. J. Clin. Oncol. 24, 1568–1574 (2006).

    Article  PubMed  Google Scholar 

  78. Nottage, K. et al. Secondary colorectal carcinoma after childhood cancer. J. Clin. Oncol. 30, 2552–2558 (2012).

    Article  PubMed  Google Scholar 

  79. Henderson, T. O. et al. Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann. Intern. Med. 156, 757–766 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Travis, L. B. et al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J. Natl Cancer Inst. 87, 524–530 (1995).

    Article  CAS  PubMed  Google Scholar 

  81. Bermejo, J. L., Sundquist, J. & Hemminki, K. Bladder cancer in cancer patients: population-based estimates from a large Swedish study. Br. J. Cancer 101, 1091–1099 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Veiga, L. H. et al. Chemotherapy and thyroid cancer risk: a report from the childhood cancer survivor study. Cancer Epidemiol. Biomarkers Prev. 21, 92–101 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378, 771–784 (2011).

  84. Fisher, B. et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl Cancer Inst. 90, 1371–1388 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Cuzick, J. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11, 1135–1141 (2010).

    Article  CAS  PubMed  Google Scholar 

  86. Burstein, H. J. et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J. Clin. Oncol. 28, 3784–3796 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Witherspoon, R. P. et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N. Engl. J. Med. 321, 784–789 (1989).

    Article  CAS  PubMed  Google Scholar 

  88. Milligan, D. W. et al. Secondary leukaemia and myelodysplasia after autografting for lymphoma: results from the EBMT. EBMT Lymphoma and Late Effects Working Parties. European Group for Blood and Marrow Transplantation. Br. J. Haematol. 106, 1020–1026 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Brown, J. R. et al. Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma. J. Clin. Oncol. 23, 2208–2214 (2005).

    Article  CAS  PubMed  Google Scholar 

  90. Bhatia, S. et al. Malignant neoplasms following bone marrow transplantation. Blood 87, 3633–3639 (1996).

    CAS  PubMed  Google Scholar 

  91. Rizzo, J. D. et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 113, 1175–1183 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Curtis, R. E. et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 94, 2208–2216 (1999).

    CAS  PubMed  Google Scholar 

  93. Curtis, R. E. et al. Solid cancers after bone marrow transplantation. N. Engl. J. Med. 336, 897–904 (1997).

    Article  CAS  PubMed  Google Scholar 

  94. Krishnan, A. et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 95, 1588–1593 (2000).

    CAS  PubMed  Google Scholar 

  95. Socie, G., Baker, K. S. & Bhatia, S. Subsequent malignant neoplasms after hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 18 (Suppl.), S139–S150 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Landgren, O. et al. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation. Blood 113, 4992–5001 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jagadeesh, D., Woda, B. A., Draper, J. & Evens, A. M. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr. Treat. Options Oncol. 13, 122–136 (2012).

    Article  PubMed  Google Scholar 

  98. Friedman, D. L. et al. Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood 111, 939–944 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bhatia, S. et al. Solid cancers after bone marrow transplantation. J. Clin. Oncol. 19, 464–471 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Gallagher, G. & Forrest, D. L. Second solid cancers after allogeneic hematopoietic stem cell transplantation. Cancer 109, 84–92 (2007).

    Article  PubMed  Google Scholar 

  101. Majhail, N. S. et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117, 316–322 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Leisenring, W., Friedman, D. L., Flowers, M. E., Schwartz, J. L. & Deeg, H. J. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J. Clin. Oncol. 24, 1119–1126 (2006).

    Article  PubMed  Google Scholar 

  103. King, M. C., Marks, J. H., Mandell, J. B. & New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302, 643–646 (2003).

    Article  CAS  PubMed  Google Scholar 

  104. Stoffel, E. et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology 137, 1621–1627 (2009).

    Article  PubMed  Google Scholar 

  105. Bonadona, V. et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305, 2304–2310 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. Metcalfe, K. A. et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol. Oncol. 96, 222–226 (2005).

    Article  CAS  PubMed  Google Scholar 

  107. Levi, F., Te, V. C., Randimbison, L. & La Vecchia, C. Cancer risk in women with previous breast cancer. Ann. Oncol. 14, 71–73 (2003).

    Article  CAS  PubMed  Google Scholar 

  108. Rhiem, K. et al. The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study. Breast Cancer Res. 14, R156 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Reiner, A. S. et al. Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: a report from the women's environmental cancer and radiation epidemiology study. J. Clin. Oncol. 31, 433–439 (2013).

    Article  PubMed  Google Scholar 

  110. Domchek, S. M. et al. Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer. Cancer http://dx.doi.org/10.1002/cncr.27842.

  111. Win, A. K. et al. Risks of primary extracolonic cancers following colorectal cancer in Lynch syndrome. J. Natl Cancer Inst. 104, 1363–1372 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Parry, S. et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut 60, 950–957 (2011).

    Article  PubMed  Google Scholar 

  113. Kastan, M. B. DNA damage responses: mechanisms and roles in human disease: 2007 G. H. A. Clowes Memorial Award Lecture. Mol. Cancer Res. 6, 517–524 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Nutting, C. et al. A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy? Clin. Oncol. (R. Coll. Radiol) 12, 300–304 (2000).

    CAS  Google Scholar 

  115. Limacher, J. M., Frebourg, T., Natarajan-Ame, S. & Bergerat, J. P. Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int. J. Cancer 96, 238–242 (2001).

    Article  CAS  PubMed  Google Scholar 

  116. Birch, J. M. et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20, 4621–4628 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Talwalkar, S. S. et al. Myelodysplastic syndromes arising in patients with germline TP53 mutation and Li-Fraumeni syndrome. Arch. Pathol. Lab. Med. 134, 1010–1015 (2010).

    PubMed  Google Scholar 

  118. Link, D. C. et al. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA 305, 1568–1576 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Kleinerman, R. A. et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J. Clin. Oncol. 23, 2272–2279 (2005).

    Article  PubMed  Google Scholar 

  120. Draper, G. J., Sanders, B. M. & Kingston, J. E. Second primary neoplasms in patients with retinoblastoma. Br. J. Cancer 53, 661–671 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sharif, S. et al. Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J. Clin. Oncol. 24, 2570–2575 (2006).

    Article  PubMed  Google Scholar 

  122. Evans, D. G., Farndon, P. A., Burnell, L. D., Gattamaneni, H. R. & Birch, J. M. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br. J. Cancer 64, 959–961 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Goldstein, A. M., Yuen, J. & Tucker, M. A. Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes Control 8, 865–871 (1997).

    Article  CAS  PubMed  Google Scholar 

  124. Breslow, N. E. et al. Secondary malignant neoplasms after Wilms tumor: an international collaborative study. Int. J. Cancer 127, 657–666 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Bernstein, J. L. et al. Radiation exposure, the ATM gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study. J. Natl Cancer Inst. 102, 475–483 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Kleinerman, R. A. Radiation-sensitive genetically susceptible pediatric sub-populations. Pediatr. Radiol. 39 (Suppl. 1), S27–S31 (2009).

    Article  PubMed  Google Scholar 

  127. Allan, J. M. Genetic susceptibility to radiogenic cancer in humans. Health Phys. 95, 677–686 (2008).

    Article  CAS  PubMed  Google Scholar 

  128. Pharoah, P. D. et al. Polygenic susceptibility to breast cancer and implications for prevention. Nat. Genet. 31, 33–36 (2002).

    Article  CAS  PubMed  Google Scholar 

  129. Peto, J. Breast cancer susceptibility-a new look at an old model. Cancer Cell 1, 411–412 (2002).

    Article  CAS  PubMed  Google Scholar 

  130. Berwick, M. et al. The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study. Cancer Epidemiol. Biomarkers Prev. 15, 1520–1525 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Berwick, M. et al. Interaction of CDKN2A and sun exposure in the etiology of melanoma in the general population. J. Invest. Dermatol. 131, 2500–2503 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Bishop, D. T. et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J. Natl Cancer Inst. 9, 894–903 (2002).

    Article  Google Scholar 

  133. Di Bernardo, M. C. et al. A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nat. Genet. 40, 1204–1210 (2008).

    Article  CAS  PubMed  Google Scholar 

  134. Broderick, P. et al. IRF4 polymorphism rs872071 and risk of Hodgkin lymphoma. Br. J. Haematol. 148, 413–415 (2010).

    Article  CAS  PubMed  Google Scholar 

  135. Duffy, D. L. et al. IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am. J. Hum. Genet. 87, 6–16 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Li, S. et al. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet. 8, e1002791 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. de Martel, C. et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13, 607–615 (2012).

    Article  PubMed  Google Scholar 

  138. Wood, M. E. et al. Second malignant neoplasms: assessment and strategies for risk reduction. J. Clin. Oncol. 30, 3734–3745 (2012).

    Article  PubMed  Google Scholar 

  139. Bhatia, S. Role of genetic susceptibility in development of treatment-related adverse outcomes in cancer survivors. Cancer Epidemiol. Biomarkers Prev. 20, 2048–2067 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Allan, J. M. et al. Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy. Blood 104, 3872–3877 (2004).

    Article  CAS  PubMed  Google Scholar 

  141. Hernandez-Boluda, J. C. et al. A polymorphism in the XPD gene predisposes to leukemic transformation and new nonmyeloid malignancies in essential thrombocythemia and polycythemia vera. Blood 119, 5221–5228 (2012).

    Article  CAS  PubMed  Google Scholar 

  142. Best, T. et al. Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma. Nat. Med. 17, 941–943 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Castigliano, S. G. Influence of continued smoking on the incidence of second primary cancers involving mouth, pharynx, and larynx. J. Am. Dent. Assoc. 77, 580–585 (1968).

    Article  CAS  PubMed  Google Scholar 

  144. Parsons, A., Daley, A., Begh, R. & Aveyard, P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ 340, b5569 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Lin, K. et al. Second primary malignancy of the aerodigestive tract in patients treated for cancer of the oral cavity and larynx. Head Neck 27, 1042–1048 (2005).

    Article  PubMed  Google Scholar 

  146. Do, K. A. et al. Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer Causes Control 14, 131–138 (2003).

    Article  PubMed  Google Scholar 

  147. Gillison, M. L. et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J. Clin. Oncol. 30, 2102–2111 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Leon, X. et al. Influence of the persistence of tobacco and alcohol use in the appearance of second neoplasm in patients with a head and neck cancer. A case-control study. Cancer Causes Control 20, 645–652 (2009).

    Article  PubMed  Google Scholar 

  149. Knight, J. A. et al. Alcohol intake and cigarette smoking and risk of a contralateral breast cancer: the women's environmental cancer and radiation epidemiology study. Am. J. Epidemiol. 169, 962–968 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Li, C. I., Daling, J. R., Porter, P. L., Tang, M. T. & Malone, K. E. Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. J. Clin. Oncol. 27, 5312–5318 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Trentham-Dietz, A., Newcomb, P. A., Nichols, H. B. & Hampton, J. M. Breast cancer risk factors and second primary malignancies among women with breast cancer. Breast Cancer Res. Treat. 105, 195–207 (2007).

    Article  PubMed  Google Scholar 

  152. Levi, F., Randimbison, L., La Vecchia, C., Erler, G. & Te, V. C. Incidence of invasive cancers following squamous cell skin cancer. Am. J. Epidemiol. 146, 734–739 (1997).

    Article  CAS  PubMed  Google Scholar 

  153. Titus-Ernstoff, L. et al. Multiple primary melanoma: two-year results from a population-based study. Arch. Dermatol. 142, 433–438 (2006).

    Article  PubMed  Google Scholar 

  154. Rigel, D. S., Friedman, R. J. & Kopf, A. W. The incidence of malignant melanoma in the United States: issues as we approach the 21st century. J. Am. Acad. Dermatol. 34, 839–847 (1996).

    Article  CAS  PubMed  Google Scholar 

  155. Majed, B., Dozol, A., Ribassin-Majed. L., Senouci, K. & Asselain, B. Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association. Breast Cancer Res. Treat. 126, 729–738 (2011).

    Article  PubMed  Google Scholar 

  156. Sanchez, L. et al. Risk factors for second primary tumours in breast cancer survivors. Eur. J. Cancer Prev. 17, 406–413 (2008).

    Article  PubMed  Google Scholar 

  157. Rock, C. L. et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J. Clin. 62, 243–274 (2012).

    Article  PubMed  Google Scholar 

  158. Mayne, S. T. et al. Randomized trial of supplemental beta-carotene to prevent second head and neck cancer. Cancer Res. 61, 1457–1463 (2001).

    CAS  PubMed  Google Scholar 

  159. Bairati, I. et al. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int. J. Cancer 119, 2221–2224 (2006).

    Article  CAS  PubMed  Google Scholar 

  160. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective [online], (2007).

  161. Smith, R. A. et al. Cancer screening in the United States, a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J. Clin. 61, 8–30 (2011).

    Article  PubMed  Google Scholar 

  162. Hewitt, M. & Ganz, P. A. (Eds) From Cancer Patient to Cancer Survivor, Lost in Transition: An American Society of Clinical Oncology and Institute of Medicine Symposium (The National Academies Press, 2006).

    Google Scholar 

  163. Saslow, D. et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J. Clin. 57, 75–89 (2007).

    Article  PubMed  Google Scholar 

  164. Warner, E. et al. Prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging. J. Clin. Oncol. 29, 1664–1669 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365, 1687–1717 (2005).

  166. Howell, A. et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 365, 60–62 (2005).

    Article  CAS  PubMed  Google Scholar 

  167. Coates, A. S. et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98 J. Clin. Oncol. 25, 486–492 (2007).

    Article  CAS  PubMed  Google Scholar 

  168. BIG 1–98 Collaborative Group. et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N. Engl. J. Med. 361, 766–776 (2009).

  169. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9, 45–53 (2008).

  170. Cuzick, J. et al. Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J. Natl Cancer Inst. 99, 272–282 (2007).

    Article  CAS  PubMed  Google Scholar 

  171. Goss, P. E. et al. Exemestane for breast-cancer prevention in postmenopausal women. N. Engl. J. Med. 364, 2381–2391 (2011).

    Article  CAS  PubMed  Google Scholar 

  172. Fisher, B. et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J. Natl Cancer Inst. 97, 1652–1662 (2005).

    Article  CAS  PubMed  Google Scholar 

  173. Vogel, V. G. et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295, 2727–2741 (2006).

    Article  CAS  PubMed  Google Scholar 

  174. Cuzick, J. et al. Preventive therapy for breast cancer: a consensus statement. Lancet Oncol. 12, 496–503 (2011).

    Article  CAS  PubMed  Google Scholar 

  175. Pierce, J. P. et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA 298, 289–298 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Chlebowski, R. T. et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. J. Natl Cancer Inst. 98, 1767–1776 (2006).

    Article  PubMed  Google Scholar 

  177. Friedenreich, C. M., Neilson, H. K. & Lynch, B. M. State of the epidemiological evidence on physical activity and cancer prevention. Eur. J. Cancer 46, 2593–2604 (2010).

    Article  PubMed  Google Scholar 

  178. Moyer, V. A. & U.S. Preventive Services Task Force. Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann. Intern. Med. 18, 900–904 (2012).

    Article  Google Scholar 

  179. Burke, W. et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 277, 915–919 (1997).

    Article  CAS  PubMed  Google Scholar 

  180. Burke, W. et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. JAMA 277, 997–1003 (1997).

    Article  CAS  PubMed  Google Scholar 

  181. Lindor, N. M. et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296, 1507–1517 (2006).

    Article  CAS  PubMed  Google Scholar 

  182. Rosenthal, A. & Jacobs, I. Familial ovarian cancer screening. Best Pract. Res. Clin. Obstet. Gynaecol. 20, 321–338 (2006).

    Article  PubMed  Google Scholar 

  183. Collaborative Group on Epidemiological Studies of Ovarian Cancer et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 371, 303–314 (2008).

  184. Grimbizis, G. F. & Tarlatzis, B. C. The use of hormonal contraception and its protective role against endometrial and ovarian cancer. Best Pract. Res. Clin. Obstet. Gynaecol. 24, 29–38 (2010).

    Article  PubMed  Google Scholar 

  185. Hannaford, P. C. et al. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ 335, 651 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Hampel, H., Sweet, K., Westman, J. A., Offit, K. & Eng, C. Referral for cancer genetics consultation: a review and compilation of risk assessment criteria. J. Med. Genet. 41, 81–91 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Thiis-Evensen, E. et al. Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study, I. Scand. J. Gastroenterol. 34, 414–420 (1999).

    Article  CAS  PubMed  Google Scholar 

  188. Rothwell, P. M. et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376, 1741–1750 (2010).

    Article  CAS  PubMed  Google Scholar 

  189. Chan, A. T. et al. Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev. Res. (Phila) 5, 164–178 (2012).

    Article  CAS  Google Scholar 

  190. Mauch, P. et al. Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9–16, Bellagio, Italy. Eur. J. Haematol. Suppl. 66, 68–76 (2005).

    Article  Google Scholar 

  191. Aberle, D. R. et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365, 395–409 (2011).

    Article  PubMed  Google Scholar 

  192. Liede, A., Karlan, B. Y. & Narod, S. A. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J. Clin. Oncol. 22, 735–742 (2004).

    Article  CAS  PubMed  Google Scholar 

  193. Wolf, A. M. et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J. Clin. 60, 70–98 (2010).

    Article  PubMed  Google Scholar 

  194. Bishop, J. N., Harland, M., Randerson-Moor, J. & Bishop, D. T. Management of familial melanoma. Lancet Oncol. 8, 46–54 (2007).

    Article  CAS  PubMed  Google Scholar 

  195. Berwick, M., Begg, C. B., Fine, J. A., Roush, G. C. & Barnhill, R. L. Screening for cutaneous melanoma by skin self-examination. J. Natl Cancer Inst. 88, 17–23 (1996).

    Article  CAS  PubMed  Google Scholar 

  196. Travis, L. B. Outcomes in cancer survivors who develop second malignant neoplasms. J. Clin. Oncol. Podcast Archive [online], (2013).

  197. Elena, J. W. et al. Leveraging epidemiology and clinical studies of cancer outcomes: recommendations and opportunities for translational research. J. Natl Cancer Inst. 105, 85–94 (2013).

    Article  PubMed  Google Scholar 

  198. Wheeler, H. E., Maitland, M. L., Dolan, M. E., Cox, N. J. & Ratain, M. J. Cancer pharmacogenomics: strategies and challenges. Nat. Rev. Genet. 14, 23–34 (2013).

    Article  CAS  PubMed  Google Scholar 

  199. Freedman, A. N. et al. Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation. J. Natl Cancer Inst. 102, 1698–1705 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  200. National Institutes of Health, National Cancer Institute, and the LIVESTRONG Young Adult Alliance. Closing the gap: research and cancer care imperatives for adolescents and young adults with cancer [online], (2006).

  201. Travis, L. B. et al. Testicular cancer survivorship: research strategies and recommendations. J. Natl Cancer Inst. 102, 1114–1130 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  202. Choi, G. et al. Genetically mediated Nf1 loss in mice promotes diverse radiation-induced tumors modeling second malignant neoplasms. Cancer Res. 72, 6425–6434 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Freedman, A. N. et al. Cancer risk prediction models: a workshop on development, evaluation, and application. J. Natl Cancer Inst. 97, 715–723 (2005).

    Article  PubMed  Google Scholar 

  204. National Childhood Cancer Foundation. Cure Search for Children's Cancer [online], (2013).

  205. Landier, W. et al. Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines. J. Clin. Oncol. 30, 4401–4408 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  206. Armstrong, G. T. et al. Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J. Clin. Oncol. 29, 3056–3064 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Milano, M. T., Li, H., Gail, M. H., Constine, L. S. & Travis, L. B. Long-term survival among patients with Hodgkin's lymphoma who developed breast cancer: a population-based study. J. Clin. Oncol. 28, 5088–5096 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Ms Laura Finger (Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY) for expert editorial assistance.

Author information

Authors and Affiliations

Authors

Contributions

All the authors researched data for the article, made a substantial contribution to the discussion of the content, and wrote and edited the manuscript prior to submission.

Corresponding author

Correspondence to Lois B. Travis.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Travis, L., Wahnefried, W., Allan, J. et al. Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors. Nat Rev Clin Oncol 10, 289–301 (2013). https://doi.org/10.1038/nrclinonc.2013.41

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2013.41

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer