Association of First Primary Cancer With Risk of Subsequent Primary Cancer in US Adults | Oncology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States

Educational Objective
To understand risk factors for new malignancies in survivors of cancer.
1 Credit CME
Key Points

Question  What are the risks of subsequent primary cancers (SPCs) among adult-onset cancer survivors in the United States?

Findings  In this retrospective cohort study that included 1.54 million survivors with a first primary cancer (FPC) between 1992-2011 and who survived at least 5 years, the risk of developing and dying from SPCs was greater than the risk expected in the general population for 18 and 27 of the 30 FPCs among men, respectively, and for 21 and 28 of the 31 FPCs among women, respectively.

Meaning  The findings emphasize the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Abstract

Importance  The number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited.

Objective  To quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex.

Design, Setting, and Participants  A retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years.

Exposures  First primary cancer.

Main Outcomes and Measures  Incidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population.

Results  Among 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs.

Conclusions and Relevance  Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: Ahmedin Jemal, DVM, PhD, American Cancer Society, 250 Williams St NW, Atlanta, GA 30303 (ahmedin.jemal@cancer.org).

Accepted for Publication: November 5, 2020.

Correction: This article was corrected on April 16, 2021 for incorrect data in Figure 1, Figure 2, and Figure 3.

Author Contributions: Dr Sung had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sung, Yabroff, Jemal.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Sung, Jemal, Yabroff.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Sung, Hyun.

Administrative, technical, or material support: Jemal.

Supervision: Jemal.

Conflict of Interest Disclosures: None reported.

Funding/Support: Supported by the Intramural Research Department of the American Cancer Society (Drs Sung, Leach, Yabroff, and Jemal).

Role of the Funder/Sponsor: The American Cancer Society had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Miller  KD , Nogueira  L , Mariotto  AB ,  et al.  Cancer treatment and survivorship statistics, 2019.   CA Cancer J Clin. 2019;69(5):363-385. doi:10.3322/caac.21565PubMedGoogle ScholarCrossref
2.
Bluethmann  SM , Mariotto  AB , Rowland  JH .  Anticipating the “Silver Tsunami”: prevalence trajectories and comorbidity burden among older cancer survivors in the United States.   Cancer Epidemiol Biomarkers Prev. 2016;25(7):1029-1036. doi:10.1158/1055-9965.EPI-16-0133PubMedGoogle ScholarCrossref
3.
El-Shami  K , Oeffinger  KC , Erb  NL ,  et al.  American Cancer Society Colorectal Cancer Survivorship Care Guidelines.   CA Cancer J Clin. 2015;65(6):428-455. doi:10.3322/caac.21286PubMedGoogle ScholarCrossref
4.
Curtis  RE , Freedman  DM , Ron  E ,  et al, eds.  New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute; 2006. NIH publication 05-5302.
5.
Murphy  CC , Gerber  DE , Pruitt  SL .  Prevalence of prior cancer among persons newly diagnosed with cancer: an initial report from the Surveillance, Epidemiology, and End Results Program.   JAMA Oncol. 2018;4(6):832-836. doi:10.1001/jamaoncol.2017.3605PubMedGoogle ScholarCrossref
6.
Bright  CJ , Reulen  RC , Winter  DL ,  et al.  Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study.   Lancet Oncol. 2019;20(4):531-545. doi:10.1016/S1470-2045(18)30903-3PubMedGoogle ScholarCrossref
7.
Lee  JS , DuBois  SG , Coccia  PF , Bleyer  A , Olin  RL , Goldsby  RE .  Increased risk of second malignant neoplasms in adolescents and young adults with cancer.   Cancer. 2016;122(1):116-123. doi:10.1002/cncr.29685PubMedGoogle ScholarCrossref
8.
Hessol  NA , Whittemore  H , Vittinghoff  E ,  et al.  Incidence of first and second primary cancers diagnosed among people with HIV, 1985-2013: a population-based, registry linkage study.   Lancet HIV. 2018;5(11):e647-e655.PubMedGoogle ScholarCrossref
9.
Adjei Boakye  E , Buchanan  P , Hinyard  L ,  et al.  Trends in the risk and burden of second primary malignancy among survivors of smoking-related cancers in the United States.   Int J Cancer. 2019;145(1):143-153. doi:10.1002/ijc.32101PubMedGoogle ScholarCrossref
10.
Gilbert  DC , Wakeham  K , Langley  RE , Vale  CL .  Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis.   Br J Cancer. 2019;120(2):256-268. doi:10.1038/s41416-018-0273-9PubMedGoogle ScholarCrossref
11.
National Cancer Institute Surveillance, Epidemiology, and End Results Program.  SEER*Stat Database: Incidence—SEER Research Plus Data. 9 Registries, November 2019 submission (1975-2017)—linked to county attributes—total US, 1969-2018 counties. Accessed August 25, 2020. http://www.seer.cancer.gov
12.
National Cancer Institute Surveillance, Epidemiology, and End Results Program.  SEER*Stat Database: Incidence—SEER Research Plus Data. 13 Registries (excluding Arkansas), November 2019 submission (1992-2017)—linked to county attributes—total US, 1969-2018 counties. Accessed October 16, 2020. http://www.seer.cancer.gov
13.
National Cancer Institute Surveillance, Epidemiology, and End Results Program.  SEER*Stat Database: Incidence—SEER Research Plus Data. 13 Registries (excluding Arkansas), November 2019 submission (1992-2017) for SMRs—linked to county attributes—total US, 1969-2018 counties. Accessed August 25, 2020. http://www.seer.cancer.gov
14.
Johnson  C , Peace  S , Adamo  P , Fritz  A , Percy-Laurry  A , Edwards  BK .  Multiple Primary and Histology Coding Rules: January 1, 2007. National Cancer Institute, Surveillance, Epidemiology and End Results Program. Accessed October 10, 2020. https://seer.cancer.gov/tools/mphrules/2007_mphrules_manual_08242012.pdf
15.
United Nations Scientific Committee on the Effects of Atomic Radiation.  Effects of Ionizing Radiation. Annex A: Epidemiological Studies of Radiation and Cancer, Volume 1. United Nations; 2006. Accessed October 10, 2020. https://www.unscear.org/docs/publications/2006/UNSCEAR_2006_Annex-A-CORR.pdf
16.
US Department of Health and Human Services.  Smoking Cessation: A Report of the Surgeon General. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2020.
17.
Lauby-Secretan  B , Scoccianti  C , Loomis  D , Grosse  Y , Bianchini  F , Straif  K ; International Agency for Research on Cancer Handbook Working Group.  Body fatness and cancer—viewpoint of the IARC Working Group.   N Engl J Med. 2016;375(8):794-798. doi:10.1056/NEJMsr1606602PubMedGoogle ScholarCrossref
18.
World Cancer Research Fund/American Institute for Cancer Research.  Continuous Update Project Expert Report 2018. Alcoholic drinks and the risk of cancer. Accessed October 10, 2020. https://www.wcrf.org/dietandcancer/recommendations/limit-alcohol-consumption
19.
Bouvard  V , Baan  R , Straif  K ,  et al; WHO International Agency for Research on Cancer Monograph Working Group.  A review of human carcinogens—part B: biological agents.   Lancet Oncol. 2009;10(4):321-322. doi:10.1016/S1470-2045(09)70096-8PubMedGoogle ScholarCrossref
20.
Yasui  Y , Liu  Y , Neglia  JP ,  et al.  A methodological issue in the analysis of second-primary cancer incidence in long-term survivors of childhood cancers.   Am J Epidemiol. 2003;158(11):1108-1113. doi:10.1093/aje/kwg278PubMedGoogle ScholarCrossref
21.
National Cancer Institute Surveillance, Epidemiology, and End Results Program.  SEER*Stat software version 8.3.6. Accessed October 10, 2020. https://www.seer.cancer.gov/seerstat
22.
National Cancer Institute Surveillance, Epidemiology, and End Results Program.  Variable and Recode Definitions on the SEER Historic Stage A. Accessed October 10, 2020. https://seer.cancer.gov/seerstat/variables/seer/yr1973_2009/lrd_stage/index.html
23.
Travis  LB , Demark Wahnefried  W , Allan  JM , Wood  ME , Ng  AK .  Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors.   Nat Rev Clin Oncol. 2013;10(5):289-301. doi:10.1038/nrclinonc.2013.41PubMedGoogle ScholarCrossref
24.
Morton  LM , Dores  GM , Schonfeld  SJ ,  et al.  Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era.   JAMA Oncol. 2019;5(3):318-325. doi:10.1001/jamaoncol.2018.5625PubMedGoogle ScholarCrossref
25.
Berrington de Gonzalez  A , Gilbert  E , Curtis  R ,  et al.  Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship.   Int J Radiat Oncol Biol Phys. 2013;86(2):224-233. doi:10.1016/j.ijrobp.2012.09.001PubMedGoogle ScholarCrossref
26.
Dracham  CB , Shankar  A , Madan  R .  Radiation induced secondary malignancies: a review article.   Radiat Oncol J. 2018;36(2):85-94. doi:10.3857/roj.2018.00290PubMedGoogle ScholarCrossref
27.
National Cancer Institute.  Cancer Trends Progress Report: Life After Cancer. Accessed August 15, 2020. https://www.progressreport.cancer.gov/after
28.
Gritz  ER , Talluri  R , Fokom Domgue  J , Tami-Maury  I , Shete  S .  Smoking behaviors in survivors of smoking-related and non–smoking-related cancers.   JAMA Netw Open. 2020;3(7):e209072. doi:10.1001/jamanetworkopen.2020.9072PubMedGoogle Scholar
29.
Gallaway  MS , Glover-Kudon  R , Momin  B ,  et al.  Smoking cessation attitudes and practices among cancer survivors—United States, 2015.   J Cancer Surviv. 2019;13(1):66-74. doi:10.1007/s11764-018-0728-2PubMedGoogle ScholarCrossref
30.
Druesne-Pecollo  N , Touvier  M , Barrandon  E ,  et al.  Excess body weight and second primary cancer risk after breast cancer: a systematic review and meta-analysis of prospective studies.   Breast Cancer Res Treat. 2012;135(3):647-654. doi:10.1007/s10549-012-2187-1PubMedGoogle ScholarCrossref
31.
Gibson  TM , Park  Y , Robien  K ,  et al.  Body mass index and risk of second obesity-associated cancers after colorectal cancer: a pooled analysis of prospective cohort studies.   J Clin Oncol. 2014;32(35):4004-4011. doi:10.1200/JCO.2014.56.8444PubMedGoogle ScholarCrossref
32.
Anderson  C , Sandler  DP , Weinberg  CR ,  et al.  Age- and treatment-related associations with health behavior change among breast cancer survivors.   Breast. 2017;33:1-7. doi:10.1016/j.breast.2017.02.013PubMedGoogle ScholarCrossref
33.
Rai  A , Chawla  N , Han  X ,  et al.  Has the quality of patient-provider communication about survivorship care improved?   J Oncol Pract. 2019;15(11):e916-e924. doi:10.1200/JOP.19.00157PubMedGoogle ScholarCrossref
34.
Runowicz  CD , Leach  CR , Henry  NL ,  et al.  American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline.   CA Cancer J Clin. 2016;66(1):43-73. doi:10.3322/caac.21319PubMedGoogle ScholarCrossref
35.
Neumann  F , Jégu  J , Mougin  C ,  et al.  Risk of second primary cancer after a first potentially-human papillomavirus-related cancer: a population-based study.   Prev Med. 2016;90:52-58. doi:10.1016/j.ypmed.2016.06.041PubMedGoogle ScholarCrossref
36.
Mukhtar  F , Ilozumba  M , Utuama  O , Cimenler  O .  Change in pattern of secondary cancers after Kaposi sarcoma in the era of antiretroviral therapy.   JAMA Oncol. 2018;4(1):48-53. doi:10.1001/jamaoncol.2017.2395PubMedGoogle ScholarCrossref
37.
Berrington de Gonzalez  A , Kutsenko  A , Rajaraman  P .  Sarcoma risk after radiation exposure.   Clin Sarcoma Res. 2012;2(1):18. doi:10.1186/2045-3329-2-18PubMedGoogle ScholarCrossref
38.
Bryant  AK , Banegas  MP , Martinez  ME , Mell  LK , Murphy  JD .  Trends in radiation therapy among cancer survivors in the United States, 2000-2030.   Cancer Epidemiol Biomarkers Prev. 2017;26(6):963-970. doi:10.1158/1055-9965.EPI-16-1023PubMedGoogle ScholarCrossref
39.
Yabroff  KR , Lund  J , Kepka  D , Mariotto  A .  Economic burden of cancer in the United States: estimates, projections, and future research.   Cancer Epidemiol Biomarkers Prev. 2011;20(10):2006-2014. doi:10.1158/1055-9965.EPI-11-0650PubMedGoogle ScholarCrossref
40.
Harlan  LC , Hankey  BF .  The surveillance, epidemiology, and end-results program database as a resource for conducting descriptive epidemiologic and clinical studies.   J Clin Oncol. 2003;21(12):2232-2233. doi:10.1200/JCO.2003.94.023PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close