Multiple primary cancers in patients undergoing tumor-normal sequencing define novel associations Journal Article


Authors: Liu, Y. L.; Cadoo, K. A.; Mukherjee, S.; Khurram, A.; Tkachuk, K.; Kemel, Y.; Maio, A.; Belhadj, S.; Carlo, M. I.; Latham, A.; Walsh, M. F.; Dubard-Gault, M. E.; Wang, Y.; Brannon, A. R.; Salo-Mullen, E.; Sheehan, M.; Fiala, E.; Devolder, B.; Dandiker, S.; Mandelker, D.; Zehir, A.; Ladanyi, M.; Berger, M. F.; Solit, D. B.; Bandlamudi, C.; Ravichandran, V.; Bajorin, D. F.; Stadler, Z. K.; Robson, M. E.; Vijai, J.; Seshan, V.; Offit, K.
Article Title: Multiple primary cancers in patients undergoing tumor-normal sequencing define novel associations
Abstract: Background: Cancer survivors are developing more subsequent cancers. SIR analysis found lymphoma–lung, lymphoma–uterine, tumors. We sought to characterize patients with multiple (≥2) breast–brain, and melanoma–lung pairs in women and primary cancers (MPC) to assess associations and genetic prostate–mesothelioma, prostate–sarcoma, melanoma–stomach, mechanisms. and prostate–brain pairs in men in excess of expected after account-Methods: Patients were prospectively consented (01/2013–02/ ing for synchronous tumors, known inherited cancer syndromes, 2019) to tumor-normal sequencing via a custom targeted panel and environmental exposures. Of 1,580 (36%) patients who received (MSK-IMPACT). A subset consented to return of results of ≥76 germline results, 324 (21%) had 361 pathogenic/likely pathogenic cancer predisposition genes. International Agency for Research on variants (PV), 159 (44%) in high penetrance genes. Of tumor Cancer (IARC) 2004 rules for defining MPC were applied. Tumor samples analyzed, 55% exhibited loss of heterozygosity at the pairs were created to assess relationships between cancers. Age-germline variant. In those with negative germline findings, melaadjusted, sex-specific, standardized incidence ratios (SIR) for first to noma, prostate, and breast cancers were common. second cancer event combinations were calculated using SEER Conclusions: We identified tumor pairs without known predisrates, adjusting for confounders and time of ascertainment. Assoposing mutations that merit confirmation and will require novel ciations were made with germline and somatic variants. strategies to elucidate genetic mechanisms of shared susceptibilities. Results: Of 24,241 patients, 4,340 had MPC (18%); 20% were Impact: If verified, patients with MPC with novel phenotypes synchronous. Most (80%) had two primaries; however, 4% had ≥4 may benefit from targeted cancer surveillance. © 2021 American Association for Cancer Research
Keywords: standardized incidence ratio; international agency for research on cancer
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 31
Issue: 2
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2022-02-01
Start Page: 362
End Page: 371
Language: English
DOI: 10.1158/1055-9965.Epi-21-0820
PUBMED: 34810208
PROVIDER: scopus
PMCID: PMC8825750
DOI/URL:
Notes: Article -- MSK author Vijai Joseph's first and last names are reversed on the original publication -- Export Date: 1 March 2022 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    343 Seshan
  2. Dean Bajorin
    603 Bajorin
  3. Kenneth Offit
    704 Offit
  4. Mark E Robson
    581 Robson
  5. David Solit
    656 Solit
  6. Zsofia Kinga Stadler
    293 Stadler
  7. Marc Ladanyi
    1187 Ladanyi
  8. Ahmet Zehir
    304 Zehir
  9. Vijai Joseph
    182 Joseph
  10. Michael Forman Berger
    599 Berger
  11. Angela Rose Brannon
    45 Brannon
  12. Yelena Kemel
    64 Kemel
  13. Maria Isabel Carlo
    104 Carlo
  14. Margaret Rebecca Graham Sheehan
    26 Sheehan
  15. Michael Francis Walsh
    115 Walsh
  16. Diana Lauren Mandelker
    105 Mandelker
  17. Ying Liu
    35 Liu
  18. Alicia Latham
    33 Latham
  19. Kaitlyn Ann Tkachuk
    19 Tkachuk
  20. Aliya Khurram
    10 Khurram
  21. Elise Marguerite Fiala
    7 Fiala
  22. Anna Maio
    12 Maio
  23. Yuhan Wang
    2 Wang