Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: A cohort study

被引:100
作者
Setshedi, Mashiko [2 ]
Epstein, David [2 ]
Winter, Trevor A. [4 ]
Myer, Landon [3 ]
Watermeyer, Gillian [2 ]
Hift, Richard [1 ]
机构
[1] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Div Med, ZA-4013 Durban, South Africa
[2] Univ Cape Town, Dept Med, Div Gastroenterol, ZA-7925 Cape Town, South Africa
[3] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa
[4] Stanford Univ, Med Ctr, Div Gastroenterol, Stanford, CA 94305 USA
关键词
6-mercaptopurine; azathioprine; immunosuppression; inflammatory bowel disease; malignancy; skin cancer; NON-HODGKINS-LYMPHOMA; MISMATCH REPAIR; DNA-DAMAGE; AZATHIOPRINE; MALIGNANCY; THERAPY; MANAGEMENT;
D O I
10.1111/j.1440-1746.2011.06865.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Background and Aim: The thiopurines azathioprine and 6-mercaptopurine are effective in the management of patients with inflammatory bowel disease (IBD) in whom aminosalicylates, antibiotics and corticosteroids have failed to induce or maintain remission. Long-term use of these agents has been linked to a greatly increased risk of non-melanoma skin cancer and lymphatic cancer in organ transplant recipients. There is some evidence to suggest that IBD patients receiving thiopurines might be at increased risk of cancer. Our aim was to determine the incidence of cancer in a cohort of patients with IBD managed in our clinic, and to relate this to thiopurine exposure. Methods: We conducted a retrospective study based on the clinical and pathology records of patients attending a specialist IBD clinic at Groote Schuur Hospital, Cape Town, South Africa between 1960 and 2007. Results: We analyzed the records of 1084 patients. A total of 123 subjects (11.5%) had received thiopurine therapy. Cancer was identified in 51 patients (4.7%), including colorectal cancer (15 patients), melanoma (two patients), non-melanoma skin cancer (seven patients) and non-Hodgkin's lymphoma (five patients). A diagnosis of non-melanoma skin cancer was significantly associated with thiopurine exposure (odds ratio 5.0, 95% confidence interval 1.1-22.8). Six of seven non-melanoma skin cancers occurred in Caucasian patients, with a highly significant association with thiopurine use (odds ratio 12.4, 95% confidence interval 2.3-67.4). Conclusions: Patients with IBD who receive thiopurines are at increased risk of nonmelanoma skin cancer. The risk is highest in Caucasian patients, and is negligible in other groups.
引用
收藏
页码:385 / 389
页数:5
相关论文
共 41 条
[1]
Asten P, 1999, J RHEUMATOL, V26, P1705
[2]
Inflammatory dowel disease, azathioprine and skin cancer: case report and literature review [J].
Austin, AS ;
Spiller, RC .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2001, 13 (02) :193-194
[3]
De novo malignancies after kidney and liver transplantations:: Experience on 582 consecutive cases [J].
Baccarani, U ;
Adani, GL ;
Montanaro, D ;
Risaliti, A ;
Lorenzin, D ;
Avellini, C ;
Tulissi, P ;
Groppuzzo, M ;
Currò, G ;
Luvisetto, F ;
Beltrami, A ;
Bresadola, V ;
Viale, PL ;
Bresadola, F .
TRANSPLANTATION PROCEEDINGS, 2006, 38 (04) :1135-1137
[4]
Skin cancers in renal-transplant recipients occur more frequently than previously recognized in a temperate climate [J].
Bordea, C ;
Wojnarowska, F ;
Millard, PR ;
Doll, H ;
Welsh, K ;
Morris, PJ .
TRANSPLANTATION, 2004, 77 (04) :574-579
[5]
A CONTROLLED DOUBLE-BLIND-STUDY OF AZATHIOPRINE IN THE MANAGEMENT OF CROHNS-DISEASE [J].
CANDY, S ;
WRIGHT, J ;
GERBER, M ;
ADAMS, G ;
GERIG, M ;
GOODMAN, R .
GUT, 1995, 37 (05) :674-678
[6]
EKBOM A, 1991, CANCER-AM CANCER SOC, V67, P2015, DOI 10.1002/1097-0142(19910401)67:7<2015::AID-CNCR2820670731>3.0.CO
[7]
2-R
[8]
Pharmacogenomics: Translating functional genomics into rational therapeutics [J].
Evans, WE ;
Relling, MV .
SCIENCE, 1999, 286 (5439) :487-491
[9]
Increased incidence of non-Hodgkin's lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low [J].
Farrell, RJ ;
Ang, Y ;
Kileen, P ;
O'Briain, DS ;
Kelleher, D ;
Keeling, PWN ;
Weir, DG .
GUT, 2000, 47 (04) :514-519
[10]
Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine [J].
Fraser, AG ;
Orchard, TR ;
Robinson, EM ;
Jewell, DP .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2002, 16 (07) :1225-1232