Evidence map›Paper›PMID 26857527›Full record

ArticleJournal of the National Cancer Institute2016

Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways.

David C Gibbs, Irene Orlow, Jennifer I Bramson, Peter A Kanetsky, Li Luo, Anne Kricker, Bruce K Armstrong, Hoda Anton-Culver, Stephen B Gruber, Loraine D Marrett and 14 more

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Association of Inherited Genetic Variants with Multiple Primary Melanoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
  5. Assessment of the Influence of UVR in Cutaneous Melanoma.Photodermatology, photoimmunology & photomedicine · 2025
    Review
  6. Article
  7. Review
  8. Disease-Associated Risk Variants inCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021
    Article
  9. Article
  10. Article
  11. Association of Known Melanoma Risk Factors with Primary Melanoma of the Scalp and Neck.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020
    Article
  12. Non-genetic and genetic predictors of a superficial first basal cell carcinoma.Journal of the European Academy of Dermatology and Venereology : JEADV · 2019
    Article
  13. Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.The Journal of investigative dermatology · 2018
    Article
  14. Article
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 12 institutions in 5 countries.

David C GibbsDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Irene OrlowDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Jennifer I BramsonDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Peter A KanetskyDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Li LuoDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Anne KrickerDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Bruce K ArmstrongDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Hoda Anton-CulverDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Stephen B GruberDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Loraine D MarrettDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Richard P GallagherDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Roberto ZanettiDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Stefano RossoDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Terence DwyerDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Ajay SharmaDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Emily La PillaDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Lynn FromDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Klaus J BusamDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Anne E CustDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
David W OllilaDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Colin B BeggDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Marianne BerwickDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF).
Nancy E ThomasDepartment of Dermatology, University of North Carolina, Chapel Hill, NC (DCG, NET); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (NET, DWO); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY (IO, AS, ELP, KJB, CBB); Department of Surgery, University of North Carolina, Chapel Hill, NC (JIB, DWO); Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (PAK); Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM (LL, MB); Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia (AEC, AK, BKA); Department of Epidemiology, University of California, Irvine, CA (HAC); USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (SBG); Department of Population Studies and Surveillance, Cancer Care Ontario, Toronto, Ontario, Canada (LDM); Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (RPG); Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy (RZ, SR); The George Institute for Global Health, Oxford Martin School of Public Health, University of Oxford, Oxford, UK (TD); Department of Pathology, Women's College Hospital, Toronto, Ontario, Canada (LF). nthomas@med.unc.edu.
GEM Study Group
University of Sydney · AUUniversity of California, Irvine · USUniversity of Oxford · GBCancer Care Ontario · CAUNC Lineberger Comprehensive Cancer CenterUniversity of New Mexico · USUniversity of North Carolina at Chapel Hill · USBC Cancer Agency · CAGeorge Institute for Global Health · GBMoffitt Cancer Center · USNew Mexico Cancer Center · USPiedmont Reference Center for Epidemiology and Cancer Prevention · IT

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Melanoma RAS/BRAF Mutation:Heterogeneity-Risk-PrognosisR01CA112243 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI THOMAS, NANCY E. · 2005 to 2014
$5.4M
A MODEL FOR GENETIC SUSCEPTIBILITY: MELANOMAU01CA083180 · NCI · UNIVERSITY OF NEW MEXICO · PI BERWICK, MARIANNE · 1999 to 2003
$5.2M
Solar Exposure and Melanoma SurvivalR01CA112524 · NCI · UNIVERSITY OF NEW MEXICO · PI BERWICK, MARIANNE · 2005 to 2009
$2.5M
Statistical Strategies for Establishing Etiologic Heterogeneity of TumorsR01CA163251 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI BEGG, COLIN B · 2012 to 2015
$1.5M
Epidemiologic Parameters of Rare Cancer Risk FactorsR01CA098438 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI BEGG, COLIN B · 2003 to 2005
$839k
NCI NIH HHS CA098438NCI NIH HHS P30 CA008748NCI NIH HHS P30CA008748NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NCI NIH HHS P30 CA016086NCI NIH HHS P30CA016086NCI NIH HHS R01 CA098438NCI NIH HHS R01 CA112243NCI NIH HHS R01CA112243NCI NIH HHS R01CA112243-05S1NCI NIH HHS R01 CA112524NCI NIH HHS R01CA112524NCI NIH HHS R01CA112524-05S2NCI NIH HHS R01 CA163251NCI NIH HHS R33CA10704339NCI NIH HHS U01 CA083180NCI NIH HHS U01CA83180NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P30ES010126
6 · The paper itself

Abstract

backgroundSolar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown.

methodsIn the Genes, Environment and Melanoma (GEM) Study, 2103 Caucasian participants had first primary melanomas that underwent centralized pathology review. For 47 single-nucleotide polymorphisms (SNPs) previously identified as low-penetrant melanoma risk variants, we used multinomial logistic regression to compare melanoma with solar elastosis and melanoma with neval remnants simultaneously to melanoma with neither of these markers, excluding melanomas with both markers. All statistical tests were two-sided.

resultsIRF4 rs12203592 was the only SNP to pass the false discovery threshold in baseline models adjusted for age, sex, and study center. rs12203592*T was associated positively with melanoma with solar elastosis (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.18 to 1.82) and inversely with melanoma with neval remnants (OR = 0.65, 95% CI = 0.48 to 0.87) compared with melanoma with neither marker (P global = 3.78 x 10(-08)). Adjusting for phenotypic characteristics and total sun exposure hours did not materially affect rs12203592's associations. Distinct early- and late-onset age distributions were observed in patients with IRF4 rs12203592 [CC] and [TT] genotypes, respectively.

conclusionsOur findings suggest a role of IRF4 rs12203592 in pathway-specific risk for melanoma development. We hypothesize that IRF4 rs12203592 could underlie in part the bimodal age distribution reported for melanoma and linked to the divergent pathways.

Indexed as

Polymorphism, Single NucleotideAdultAgedAge of OnsetFemaleGenetic Predisposition to DiseaseGenotypeHumansInterferon Regulatory Factor-4Interferon Regulatory FactorsLogistic ModelsMaleMelanomaMiddle AgedOdds RatioPhenotypeInterferon Regulatory Factor-4Interferon Regulatory Factors

Identifiers

PMID26857527
PMCPMC4948568
OpenAlexW2300075159

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