title: Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort.
abstract: Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: A E
authors.initials: AE
authors.lastname: Coghill
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: L G
authors.initials: LG
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: D
authors.initials: D
authors.lastname: Berg
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.|School of Public Health, University of Washington, Seattle, WA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Resler
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: N
authors.initials: N
authors.lastname: Leca
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.|School of Public Health, University of Washington, Seattle, WA.
authors.forename: M M
authors.initials: MM
authors.lastname: Madeleine
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D011379:Prognosis; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D016559:Tacrolimus / Q000627:therapeutic use; D014861:Washington / Q000453:epidemiology
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: cancer, malignancy, neoplasia; clinical research, practice; immunosuppression, immune modulation; skin, nonmelanoma, epidemiology
references.citation: Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003961
references.pmid: 16235347
references.citation: Am J Transplant. 2005 Dec;5(12 ):2954-60
references.pmid: 16303010
references.citation: J Antibiot (Tokyo). 1968 Jul;21(7):463-4
references.pmid: 4303502
references.citation: JAMA. 2011 Nov 2;306(17):1891-901
references.pmid: 22045767
references.citation: BMJ. 2010 Feb 11;340:c570
references.pmid: 20150194
references.citation: Immunopharmacology. 2000 May;47(2-3):85-118
references.pmid: 10878285
references.citation: Int J Cancer. 2013 Mar 15;132(6):1429-38
references.pmid: 22886725
references.citation: Nat Rev Nephrol. 2010 Sep;6(9):511-9
references.pmid: 20736984
references.citation: Am J Transplant. 2010 Jun;10(6):1385-93
references.pmid: 20121752
references.citation: Br J Cancer. 2008 Oct 21;99(8):1276-84
references.pmid: 18854826
references.citation: BMJ. 2014 Nov 24;349:g6679
references.pmid: 25422259
references.citation: Am J Transplant. 2010 Aug;10(8):1889-96
references.pmid: 20659094
references.citation: Transplant Proc. 1969 Mar;1(1):106-12
references.pmid: 4944206
references.citation: JAMA. 1977 Jan 10;237(2):152
references.pmid: 576155
references.citation: Transplantation. 2004 Jun 27;77(12):1777-82
references.pmid: 15223891
references.citation: Transplant Proc. 2010 Oct;42(8):3001-5
references.pmid: 20970593
references.citation: Immunobiology. 1989 Feb;178(4-5):401-15
references.pmid: 2785485
references.citation: Swiss Med Wkly. 2010 Jul 15;140:w13036
references.pmid: 20652847
references.citation: Br J Dermatol. 2002 Nov;147(5):950-6
references.pmid: 12410706
references.citation: J Lab Clin Med. 2001 Jan;137(1):14-20
references.pmid: 11150019
references.citation: Br J Dermatol. 2008 Jul;159(1):198-204
references.pmid: 18489587
references.citation: Transplantation. 1987 Sep;44(3):429-34
references.pmid: 3629691
references.citation: N Engl J Med. 2003 Apr 24;348(17):1681-91
references.pmid: 12711744
references.citation: Transplantation. 2006 Apr 27;81(8):1093-100
references.pmid: 16641592
references.citation: Am J Transplant. 2004 Jun;4(6):905-13
references.pmid: 15147424
references.citation: Cancer Epidemiol. 2012 Apr;36(2):e69-73
references.pmid: 22236649
references.citation: Arch Dermatol. 2004 Sep;140(9):1079-85
references.pmid: 15381547
references.citation: Lancet. 1971 May 15;1(7707):983-6
references.pmid: 4102451
references.citation: Clin Transplant. 2005 Apr;19(2):279-85
references.pmid: 15740568
references.citation: Clin Transpl. 2000;:193-202
references.pmid: 11512313
references.citation: Int J Cancer. 1994 May 15;57(4):568-73
references.pmid: 8181860
references.citation: N Engl J Med. 2004 Dec 23;351(26):2715-29
references.pmid: 15616206
references.citation: Lancet. 2007 Jul 7;370(9581):59-67
references.pmid: 17617273
references.citation: Nucleic Acids Res. 2009 Apr;37(6):1951-61
references.pmid: 19208641
references.citation: Transpl Int. 2006 Aug;19(8):607-20
references.pmid: 16827677
references.citation: Carcinogenesis. 1993 Aug;14(8):1579-84
references.pmid: 8353842
references.citation: Transplantation. 1998 Aug 27;66(4):493-9
references.pmid: 9734494
references.citation: Int J Epidemiol. 2013 Dec;42(6):1669-77
references.pmid: 23171871
references.citation: J Am Acad Dermatol. 2002 Jul;47(1):1-17; quiz 18-20
references.pmid: 12077575
references.citation: Br J Dermatol. 2012 Aug;167 Suppl 2:53-62
references.pmid: 22881588
references.citation: Transplantation. 2003 Aug 15;76(3):597-602
references.pmid: 12923450
references.citation: Exp Dermatol. 2011 Mar;20(3):232-6
references.pmid: 21323745
references.citation: Transplant Proc. 2010 Oct;42(8):3055-7
references.pmid: 20970609
references.citation: Nature. 1999 Feb 11;397(6719):530-4
references.pmid: 10028970
references.citation: Dermatol Surg. 2004 Apr;30(4 Pt 2):622-7
references.pmid: 15061846
references.citation: Transplantation. 1997 Aug 15;64(3):436-43
references.pmid: 9275110
references.citation: Transplant Proc. 2003 Aug;35(5):1714-6
references.pmid: 12962768
references.citation: Am J Transplant. 2015 Jan;15(1):129-36
references.pmid: 25522018
references.citation: Exp Dermatol. 2011 Oct;20(10):795-9
references.pmid: 21707758
references.citation: Lancet. 1998 Feb 28;351(9103):623-8
references.pmid: 9500317
references.citation: Transplantation. 2014 Sep 27;98(6):646-52
references.pmid: 24798309
references.citation: Exp Dermatol. 2008 Apr;17(4):349-55
references.pmid: 17979968