Editing Azathioprine (section)

===Cancers===
Azathioprine is listed as a human carcinogen in the 12th Report on Carcinogens by the [[National Toxicology Program]] of [[United States Department of Health and Human Services|U.S. Department of Health and Human Services]], asserting that it is "known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans."<ref name="roc2011">{{cite web|author=National Toxicology Program|author-link=National Toxicology Program|title=Report On Carcinogens – Twelfth Edition – 2011|date=10 June 2011|url=https://ntp.niehs.nih.gov/go/roc12|publisher=[[National Toxicology Program]]|access-date=June 20, 2012|url-status=live|archive-url=https://web.archive.org/web/20120716214414/http://ntp.niehs.nih.gov/ntp/roc/twelfth/roc12.pdf|archive-date=16 July 2012}}</ref> Since August 2009, the U.S. FDA has required warnings to be placed on packaging with respect to increased risks of certain cancers.<ref>{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm175803.htm |title=FDA: Cancer Warnings Required for TNF Blockers |date=August 4, 2009 |publisher=FDA |access-date=June 20, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120703083928/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm175803.htm |archive-date=July 3, 2012 }}</ref>

The risks involved seem to be related both to the duration and the dosage used. People who have previously been treated with an [[alkylating antineoplastic agent|alkylating agent]] may have an excessive risk of cancers if treated with azathioprine. Epidemiological studies by [[International Agency for Research on Cancer]] have provided "sufficient" evidence of azathioprine carcinogenicity in humans ([[List of IARC Group 1 carcinogens|group 1]]),<ref name="IARC-1981">{{cite journal| author = International Agency for Research on Cancer (IARC)| author-link = International Agency for Research on Cancer| year = 1981| url = http://www.inchem.org/documents/iarc/vol26/azathioprine.html| title = Azathioprine – 5. Summary of Data Reported and Evaluation| journal = Summaries & Evaluations| volume = 26| page = 47| url-status = live| archive-url = https://web.archive.org/web/20060906064533/http://www.inchem.org/documents/iarc/vol26/azathioprine.html| archive-date = 2006-09-06}}</ref> although the methodology of past studies and the possible underlying mechanisms are questioned.<ref name="MutatRes1993-Gombar">{{cite journal | vauthors = Gombar VK, Enslein K, Blake BW | title = Carcinogenicity of azathioprine: an S-AR investigation | journal = Mutation Research | volume = 302 | issue = 1 | pages = 7–12 | date = May 1993 | pmid = 7683109 | doi = 10.1016/0165-7992(93)90083-8 }}</ref>

The various diseases requiring transplantation may in themselves increase the risks of [[non-Hodgkin lymphoma]], [[squamous cell carcinoma]]s of the skin, [[Cholangiocarcinoma|hepatobiliary carcinomas]], and [[Mesenchyme|mesenchymal tumours]] to which azathioprine may add additional risks. Those receiving azathioprine for rheumatoid arthritis may have a lower risk than those undergoing transplantation.<ref name="IARC-1987">{{cite journal| author = International Agency for Research on Cancer (IARC)| author-link = International Agency for Research on Cancer| year = 1987| url = http://www.inchem.org/documents/iarc/suppl7/azathioprine.html| title = Azathioprine| journal = Summaries & Evaluations| issue = suppl. 7| page = 119| url-status = live| archive-url = https://web.archive.org/web/20060604004241/http://www.inchem.org/documents/iarc/suppl7/azathioprine.html| archive-date = 2006-06-04}}</ref>

Cases of [[hepatosplenic T-cell lymphoma]] – a rare type of [[lymphoma]] – have been reported in patients treated with azathioprine. The majority occurred in patients with inflammatory bowel disease. Adolescents and young adult males were the majority of cases.<ref name="gut">{{cite journal | vauthors = McGovern DP, Jewell DP | title = Risks and benefits of azathioprine therapy | journal = Gut | volume = 54 | issue = 8 | pages = 1055–1059 | date = August 2005 | pmid = 16009676 | pmc = 1774869 | doi = 10.1136/gut.2004.053231 }}</ref> They presented with a very aggressive disease course, and with one exception, died of the lymphoma. The FDA has required changes to the labeling to inform users and clinicians of the issue.<ref>{{cite web |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm258794.htm |title=Imuran (azathioprine) Tablets and Injection |date=May 2011 |publisher=FDA |access-date=June 20, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120302092152/https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm258794.htm |archive-date=March 2, 2012 }}</ref>

====Skin cancers====
In transplant patients, [[skin cancer]] is 50 to 250 times more common than in the general population, and between 60 and 90% of patients are affected 20 years after transplantation. The use of immunosuppressive medication including azathioprine in organ transplantation has been linked to increased rates of developing skin cancer.<ref name="bbcsb">{{cite web |url=http://news.bbc.co.uk/2/hi/health/4248356.stm |title=Skin cancer alert for organ drug |date=September 15, 2005 |website=[[BBC Online]] |publisher=[[BBC News]] |access-date=June 10, 2012 |url-status=live |archive-url=https://web.archive.org/web/20121014205054/http://news.bbc.co.uk/2/hi/health/4248356.stm |archive-date=October 14, 2012 }}</ref> Azathioprine causes the accumulation of [[6-thioguanine]] (6-TG) in patients' DNA, which might trigger cancer when the patient is later exposed to [[ultraviolet light]]. Patients taking azathioprine were found to be abnormally sensitive to UVA light.<ref>{{cite journal | vauthors = O'Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P | title = Azathioprine and UVA light generate mutagenic oxidative DNA damage | journal = Science | volume = 309 | issue = 5742 | pages = 1871–1874 | date = September 2005 | pmid = 16166520 | pmc = 2426755 | doi = 10.1126/science.1114233 | bibcode = 2005Sci...309.1871O }}</ref>