Incidence of nonmelanoma skin cancer in renal transplant recipients: A systematic review and meta-analysis
Mohammad Matinfar1, Shahrzad Shahidi2, Awat Feizi3
1 Department of Internal Medicine, Division of Nephrology, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Internal Medicine, Division of Nephrology, Isfahan University of Medical Sciences; Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Isfahan Endocrine and Metabolism Research Center and Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||10-Sep-2017|
|Date of Decision||04-Oct-2017|
|Date of Acceptance||06-Nov-2017|
|Date of Web Publication||20-Feb-2018|
Dr. Shahrzad Shahidi
Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Nonmelanoma skin cancer (NMSC) in renal transplant recipients is common and associated with significant morbidity and mortality. The aim of the present systematic review and meta-analysis was to estimate the incidence of NMSC among renal transplant recipients. Materials and Methods: We systematically searched PubMed, Medline, Scopus, and Web of Science databases for studies that assessed the incidence of NMSC in renal transplant recipients using a combination of relevant keywords. Two independent investigators included studies and extracted necessary information. Random effect meta-analysis was used to estimate pooled incidence of NMSC with 95% confidence intervals (CIs). Results: Twenty-nine studies comprising 36,021 patients meet the criteria for the systematic review. The pooled incidence of NMSC in renal transplant recipients was 12.6% (95% CI: 12%–14%) with a majority of squamous cell carcinoma (SCC) 55% (95% CI: 47%–63%). The pooled estimate of the incidence rates of SCC and basal cell carcinoma was 2.7% (95% CI: 2%–3.4%) and 2.2% (95% CI: 1.5%–2.8%), respectively. Subgroup analysis per geographic location showed that pooled incidence of NMSC was 39.1% (95% CI: 26.3%–51.8%), 12.4% (95% CI: 8.8%–16%), and 1.2% (95% CI: 0.4%–2%) in Australia and New Zealand, Europe, and Middle East, respectively. Conclusion: The results of the current meta-analysis demonstrated that the incidence of NMSC in renal transplant recipients varies widely. Regarding the high incidence of NMSC among renal transplant recipients, awareness of associated risk factors and early diagnosis of the malignancy in the population is a major clinical need.
Keywords: Basal cell carcinoma, incidence, nonmelanoma skin cancer, renal transplantation, squamous cell carcinoma
|How to cite this article:|
Matinfar M, Shahidi S, Feizi A. Incidence of nonmelanoma skin cancer in renal transplant recipients: A systematic review and meta-analysis. J Res Med Sci 2018;23:14
|How to cite this URL:|
Matinfar M, Shahidi S, Feizi A. Incidence of nonmelanoma skin cancer in renal transplant recipients: A systematic review and meta-analysis. J Res Med Sci [serial online] 2018 [cited 2018 Dec 13];23:14. Available from: http://www.jmsjournal.net/text.asp?2018/23/1/14/225904
| Introduction|| |
Renal transplantation has been considered the preferred treatment option regarding its positive impacts on patients' life expectancy and quality of life., The introduction of more potent immunosuppressive drugs has improved the outcome of renal transplantation. However, posttransplant malignancies can arise as a result of continuous exposure to immunosuppressive drugs., Nonmelanoma skin cancer (NMSC), predominantly squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is one of the most malignancies following renal transplantation.,
A recent meta-analysis by Shang et al. has evaluated the cancer risk in patients receiving renal replacement therapy. The results of the meta-analysis indicated that there is an association between renal transplantation and an increased risk of NMSC. Although the existing literature has provided relevant insights, some important questions remain to be answered. First of all, the estimate of the total incidence of NMSC among renal transplant recipients as well as across subgroups for this high-risk population is remained unclear. In addition, the incidence of SCC and BCC as the most frequent skin cancers in renal transplant recipients has not been elucidated. Accordingly, the aim of the present systematic review and meta-analysis is to estimate the incidence of NMSC among renal transplant recipients totally and across different important subgroups (if data are available). We will also ascertain the incidence of SCC and BCC among this population which provides useful information for clinicians.
| Materials and Methods|| |
A systematic search of literature was performed using a number of resources including PubMed, Medline, Scopus, and Web of Science databases. The search strategy included the following key terms: renal or kidney, transplant or transplantation or allograft, non-melanoma skin cancer or nonmelanoma skin cancer or NMSC. We did not apply any language or time restrictions, and the final search was conducted in February 2017. The reference list of all eligible articles was reviewed to detect further relevant articles.
Inclusion and exclusion criteria
The titles and abstracts of searched articles were reviewed by two independent authors (MM and SS). Studies were eligible if they meet the following inclusion criteria: (a) population-based studies on renal transplant recipients and (b) studies that provided incidence rate of NMSC or enough information to calculate incidence rates. The exclusion criteria were as follow: (a) studies on transplantation of organs other than kidney and (b) case reports, review articles, conference reports, and letters. If there were several publications on the same study, we used the most comprehensive one with the largest sample size or the longest follow-up time.
Data extraction and quality assessment
Two reviewers (MM and SS) independently performed data extraction, and any disagreements were picked up by a third author (AF). The following data were extracted from each study using standardized collection forms: first author, publication date, region, study design, sample size, sex, follow-up period, mean age at transplantation, number of NMSC, SCC, and BCC (where available), and incidence of NMSC, SCC, and BCC.
Two independent investigators assessed the quality of included studies. Investigators discussed their controversies and any disagreements were resolved through discussion and reevaluation.
To estimate the overall incidence and in subgroup meta-analyses, “metaprop program” in STATA version 14.0 (STATA, College Station, TX, USA) statistical software was used. In this modeling approach, the incidence was estimated using pooling binomial data, and 95% confidence interval (CI) for incidence was constructed using score method.
Heterogeneity was evaluated using the Cochran Chi-square test and the Cochrane-I2 statistics as well as visual inspection of forest plot. Values of 25%, 50%, and 75% for I2 were considered as low, medium, and high levels of heterogeneity, respectively. Data were pooled using random effects model due to high levels of heterogeneity among included studies. Possible sources of heterogeneity were explored by sensitivity and meta-regression, if possible, by subgroup analyses (based on geographic location and study design) and could be related to the duration of follow-up and mean age of participants.
In current meta-analysis, publication bias was assessed by examining asymmetry in Begg funnel plots and conducting weighted Egger linear regression method, which suggested that the selection of publication was a likely source of bias. The sources of publication bias were also evaluated using sensitivity analysis, in which each individual study was removed from analyses.
| Results|| |
Twenty-nine eligible studies comprising a total of 36,021 renal transplant recipients were included in the current meta-analysis [Figure 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,, Of the 29 publications, 25 were used for estimating the incidence of NMSC ,,,,,,,,,,,,,,,,,,,,,,,,, whereas 11 publications were included to estimate the incidence of SCC and BCC.,,,,,,,,,, Basic characteristics of included studies are presented in [Table 1].
|Table 1: Characteristics of included studies in the present meta-analysis|
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Majority of included studies had been performed in Europe (n = 19),,,,,,,,,,,,,,,,,,, four in Australia and New Zealand,,,, three in Middle East,,, and three in South Africa, Brazil, and Canada. There were 16 retrospective cohort studies,,,,,,,,,,,,,,,, 12 prospective cohort studies.,,,,,,,,,,, The mean age at transplantation and follow-up period ranged from 37 to 52.2 and 1.5 to 27.75 years, respectively. A total number of 1948 subjects developed NMSC in selected studies [Table 1].
| Meta-Analysis and Quantitative Results|| |
The Cochran Q statistics (P< 0.001) and I2 statistic indicated higher levels of heterogeneity (I2 >90%) among included studies in meta-analysis for total incidence estimating as well as in all considered subgroup meta-analyses accordingly, all analyses were conducted in random-effect meta-analysis modeling approach.
The pooled incidence of NMSC was 12.6% in renal transplant recipients (95% CI: 11%–14.2%); however, the analysis showed significant heterogeneity across studies (I2 = 98.94, P < 0.001) [Figure 2]. The sensitivity analysis indicated the exclusion of two studies , led to a pooled estimate of 10% (95% CI: 8.6%–11.4%) (I2 = 98.69, P < 0.001). The pooled estimate of the proportion of tumors revealed that 55% (95% CI: 47%–63%) (I2 = 96.72, P < 0.001) and 36% (95% CI: 30%–42%) (I2 = 94.05, P < 0.001) of all NMSCs were SCC and BCC, respectively [Figure 3]a and [Figure 3]b. Our results also indicated that the pooled proportion of patients with SCC and BCC were 44% (95% CI: 30.9%–57.2%) (I2 = 94.11, P < 0.001) and 38.3% (95% CI: 21%–55.7%) (I2 = 96.89, P < 0.001), respectively [Figure 4]a and [Figure 4]b.
|Figure 2: Forest plot for pooled estimate of incidence of nonmelanoma skin cancer incidence in renal transplant recipients|
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|Figure 3: (a) Forest plot for pooled estimated proportion of squamous cell carcinoma tumors and (b) Forest plot for pooled estimated proportion of basal cell carcinoma tumors|
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|Figure 4: (a) Forest plot for pooled estimated proportion of patients with squamous cell carcinoma and (b) Forest plot for pooled estimated proportion of patients with basal cell carcinoma|
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The pooled incidence rates of SCC and BCC were 2.7% (95% CI: 2%–3.4%) (I2 = 97.77, P < 0.001) and 2.2% (95% CI: 1.5%–2.8%) (I2 = 97.67, P < 0.001) respectively [Figure 5]a and [Figure 5]b. The sensitivity analysis revealed that omission of studies with the highest incidence rate , led to changes in estimated pooled incidence of 1.2% (95% CI: 0.8%–1.6%) (I2 = 93.01, P < 0.001) and 0.8% (95% CI: 0.5%–1.1%) (I2 = 91.49, P < 0.001) for SCC and BCC, respectively.
|Figure 5: (a) Forest plot for pooled estimated incidence of squamous cell carcinoma and (b) Forest plot for pooled estimated incidence of basal cell carcinoma|
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We performed a subgroup analysis to explore the incidence of NMSC among renal transplant recipients in various geographic regions. The results of subgroup analysis per geographic location indicated that pooled incidence of NMSC was 39.1% (95% CI: 26.3%–51.8%) (I2 = 95.34, P < 0.001), 12.4% (95% CI: 8.8%–16%) (I2 = 98.49, P < 0.001), and 1.2% (95% CI: 0.4%–2%) (I2 = 96.48, P < 0.001) in Australia and New Zealand, Europe, and Middle East, respectively [Figure 6].
|Figure 6: Forest plot of pooled estimated incidence of nonmelanoma skin cancer in subgroup analysis based on geographic location|
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The results of subgroup analysis based on the study design showed that pooled estimate for NMSC was 22% for prospective (95% CI: 15%–29%) (I2 = 99.10, P < 0.001), and 9% (95% CI: 7%–12%) (I2 = 98.80, P < 0.001) for retrospective studies [Figure 7].
|Figure 7: Forest plot of estimated incidence of nonmelanoma skin cancer in subgroup analysis based on study design|
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Publication bias and sensitivity analysis and meta-regression
The funnel plots were used for examining the publication bias, no evidences were detected from the plots in one hand, and on the other hand, the results of both Begg's rank correlation method and Egger weighted regression method suggested no statistically significant asymmetry in funnel plots. Trim and fill method also was used as a complementary approach to adjust the funnel plot asymmetry, but the results showed no trimming performed and data unchanged. The meta-regression analysis for evaluating the possible cofounding effects of mean age of participants and follow-up period of included studies showed no significant associations; in other word, they could not be considered as sources of heterogeneity. Furthermore, sensitivity analyses' results showed no significant change in estimated overall incidence as well as its values in subgroup analyses in this meta-analysis after excluding studies that were considered lower quality.
| Discussion|| |
Advances in kidney transplantation have improved both graft and patients' survival. However, long-term exposure to immune suppressive drugs leads to chronic medical conditions such as posttransplant malignancies.,, The most frequent malignancy after renal transplantation is NMSC. Some factors are regarded to contribute to susceptibility for NMSC. Older age, male sex, fair skin type, ultraviolet (UV) exposure, and duration of immunosuppression are reported to be associated with the risk of NMSC in renal transplant patients.,,,,,,,
The results of the present meta-analysis indicated that the incidence of NMSC in renal transplant patients was 12% with SCC as the most predominant tumor. It is estimated that BCC and SCC comprise about 80% and 20% of all NMSC in the general population. Conversely, in renal recipient patients, the majority of NMSC are SCC with a more aggressive phenotype, higher metastatic, and recurrence rate. However, this pattern has not been seen in all of studies which have assessed NMSC incidence after renal transplantation. The most common form of NMSC has been BCC in some studies done in Spain, Portugal, or Italy.,, Possibly, a number of factors such as genetic background, patterns of sun exposure, and skin type are among factors that change the ratio of BCC/SCC among renal transplant population. In addition, regarding the linear increase in BCC incidence after renal transplantation, possibly long-term follow-up studies detect the true difference between SCC and BCC incidence among this population.
The subgroup analysis conducted for geographic locations revealed that the incidence of NMSC in Australia is 39.1%. The assessment of NMSC in general population has also shown that the incidence of the malignancy varies widely across the world with the highest incidence in Australia. One possible reason for higher incidence of NMSC among renal transplant recipients in Australia and New Zealand is higher UV radiation intensity in the location. It is detected that southern hemisphere has a greater intensity of UV radiation which its clearer skies increase it to 15%., The low incidence of NMSC among Middle East population regarding the lack of highly pigmented (Fitzpatrick V and VI) skin types and exposure to high sunlight, casting some doubts on the role of sunlight exposure as the main determinant of high NMSC risk among Australians. Previous studies have reported a potential association between the expression of some human leukocyte antigens and NMSC.,,, It also supposed that lower incidence of NMSC in renal transplant recipients in the Middle East are explained by some ethic variations such as wearing protective clothing and different sunbathing habits.
| Conclusion|| |
The results of the present meta-analysis indicated that the incidence of NMSC varies greatly in different populations. High heterogeneity was observed in various subgroups in the present meta-analysis indicating that there might be other factors such as clinical and environmental risk factors that need to be considered to explain differences in the incidence of NMSC among renal transplant recipients. Regarding the high incidence of NMSC among renal transplant recipients, awareness of associated risk factors and early diagnosis of the malignancy in the population is a major clinical need.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al.
Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N
Engl J Med 1999;341:1725-30.
Neipp M, Karavul B, Jackobs S, Meyer zu Vilsendorf A, Richter N, Becker T, et al.
Quality of life in adult transplant recipients more than 15 years after kidney transplantation. Transplantation 2006;81:1640-4.
Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M, et al.
Cancer incidence before and after kidney transplantation. JAMA 2006;296:2823-31.
Vial T, Descotes J. Immunosuppressive drugs and cancer. Toxicology 2003;185:229-40.
Penn I. Cancers in renal transplant recipients. Adv Ren Replace Ther 2000;7:147-56.
Glover MT, Niranjan N, Kwan JT, Leigh IM. Non-melanoma skin cancer in renal transplant recipients: The extent of the problem and a strategy for management. Br J Plast Surg 1994;47:86-9.
Shang W, Huang L, Li L, Li X, Zeng R, Ge S, et al.
Cancer risk in patients receiving renal replacement therapy: A meta-analysis of cohort studies. Mol Clin Oncol 2016;5:315-25.
Nyaga VN, Arbyn M, Aerts M. Metaprop: A Stata command to perform meta-analysis of binomial data. Arch Public Health 2014;72:39.
Wilson EB. Probable inference, the law of succession, and statistical inference. J Am Stat Assoc 1927;22:209-12.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
Harris R, Bradburn M, Deeks J, Harbord R, Altman D, Sterne J. Metan: Fixed-and random-effects meta-analysis. Stata J 2008;8:3.
Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, et al.
The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: A systematic review. J Evid Based Med 2015;8:2-10.
Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ 2001;323:101-5.
Hartevelt MM, Bavinck JN, Kootte AM, Vermeer BJ, Vandenbroucke JP. Incidence of skin cancer after renal transplantation in the Netherlands. Transplantation 1990;49:506-9.
Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis 2000;36:167-76.
Naldi L, Fortina AB, Lovati S, Barba A, Gotti E, Tessari G, et al.
Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study. Transplantation 2000;70:1479-84.
Harden PN, Fryer AA, Reece S, Smith AG, Ramsay HM. Annual incidence and predicted risk of nonmelanoma skin cancer in renal transplant recipients. Transplant Proc 2001;33:1302-4.
Ramsay HM, Fryer AA, Hawley CM, Smith AG, Nicol DL, Harden PN, et al.
Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia. J Am Acad Dermatol 2003;49:397-406.
Carroll RP, Ramsay HM, Fryer AA, Hawley CM, Nicol DL, Harden PN. Incidence and prediction of nonmelanoma skin cancer post-renal transplantation: A prospective study in Queensland, Australia. Am J Kidney Dis 2003;41:676-83.
Fuente MJ, Sabat M, Roca J, Lauzurica R, Fernández-Figueras MT, Ferrándiz C. Aprospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients. Br J Dermatol 2003;149:1221-6.
Moloney FJ, Almarzouqi E, O'Kelly P, Conlon P, Murphy GM. Sunscreen use before and after transplantation and assessment of risk factors associated with skin cancer development in renal transplant recipients. Arch Dermatol 2005;141:978-82.
Moosa MR, Gralla J. Skin cancer in renal allograft recipients – Experience in different ethnic groups residing in the same geographical region. Clin Transplant 2005;19:735-41.
Moloney FJ, Comber H, O'Lorcain P, O'Kelly P, Conlon PJ, Murphy GM. Apopulation-based study of skin cancer incidence and prevalence in renal transplant recipients. Br J Dermatol 2006;154:498-504.
Ramsay HM, Reece SM, Fryer AA, Smith AG, Harden PN. Seven-year prospective study of nonmelanoma skin cancer incidence in U.K. Renal transplant recipients. Transplantation 2007;84:437-9.
Stratta P, Morellini V, Musetti C, Turello E, Palmieri D, Lazzarich E, et al.
Malignancy after kidney transplantation: Results of 400 patients from a single center. Clin Transplant 2008;22:424-7.
Navarro MD, López-Andréu M, Rodríguez-Benot A, Agüera ML, Del Castillo D, Aljama P. Cancer incidence and survival in kidney transplant patients. Transplant Proc 2008;40:2936-40.
Comeau S, Jensen L, Cockfield SM, Sapijaszko M, Gourishankar S. Non-melanoma skin cancer incidence and risk factors after kidney transplantation: A Canadian experience. Transplantation 2008;86:535-41.
Mackenzie KA, Wells JE, Lynn KL, Simcock JW, Robinson BA, Roake JA, et al.
First and subsequent nonmelanoma skin cancers: Incidence and predictors in a population of New Zealand renal transplant recipients. Nephrol Dial Transplant 2010;25:300-6.
Kalinova L, Majek O, Stehlik D, Krejci K, Bachleda P. Skin cancer incidence in renal transplant recipients-a single center study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154:257-60.
Tessari G, Naldi L, Boschiero L, Nacchia F, Fior F, Forni A, et al.
Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: A multicenter cohort study. Arch Dermatol 2010;146:294-9.
Keller B, Braathen LR, Marti HP, Hunger RE. Skin cancers in renal transplant recipients: A description of the renal transplant cohort in Bern. Swiss Med Wkly 2010;140:w13036.
Bretagnol A, Halimi JM, Roland M, Barbet C, Machet L, Al Najjar A, et al.
Autosomal dominant polycystic kidney disease: Risk factor for nonmelanoma skin cancer following kidney transplantation. Transpl Int 2010;23:878-86.
Zavos G, Karidis NP, Tsourouflis G, Bokos J, Diles K, Sotirchos G, et al.
Nonmelanoma skin cancer after renal transplantation: A single-center experience in 1736 transplantations. Int J Dermatol 2011;50:1496-500.
Ng JC, Cumming S, Leung V, Chong AH. Accrual of non-melanoma skin cancer in renal-transplant recipients: Experience of a Victorian tertiary referral institution. Australas J Dermatol 2014;55:43-8.
Vrotniakaite K, Jaceviciute R, Rudminiene I, Laucyte-Cibulskiene A, Rainiene T, Jankevicius F, et al.
Malignancy after renal transplantation: A single-center experience. Ann Transplant 2014;19:456-63.
Tepeoǧlu M, Ayva Ş, Ok Atılgan A, Tunca MZ, Özdemir BH, Moray G, et al.
Nonmelanoma skin cancer after kidney transplant. Exp Clin Transplant 2014;12:233-7.
Bernat-García J, Morales Suárez-Varela M, Vilata-Corell JJ, Marquina-Vila A, Pallardo L, Crespo J. The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients. Actas Dermosifiliogr 2014;105:940-6.
Bannon FJ, McCaughan JA, Traynor C, O'Brien K, Gavin AT, Maxwell AP, et al.
Surveillance of nonmelanoma skin cancer incidence rates in kidney transplant recipients in Ireland. Transplantation 2014;98:646-52.
Gonçalves CP, Trope BM, Ramos-E-Silva M. Non-melanoma skin cancer in renal transplant recipients: A study in a Brazilian reference center. Clin Cosmet Investig Dermatol 2015;8:339-44.
Keles Y, Tekin S, Duzenli M, Yuksel Y, Yücetin L, Dosemeci L, et al.
Post-transplantation malignancy after kidney transplantation in Turkey. Transplant Proc 2015;47:1418-20.
Pinho A, Gouveia M, Cardoso JC, Xavier MM, Vieira R, Alves R. Non-melanoma skin cancer in portuguese kidney transplant recipients – Incidence and risk factors. An Bras Dermatol 2016;91:455-62.
Einollahi B, Nemati E, Lessan-Pezeshki M, Simforoosh N, Nourbala MH, Rostami Z, et al.
Skin cancer after renal transplantation: Results of a multicenter study in Iran. Ann Transplant 2010;15:44-50.
Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N
Engl J Med 2005;352:1371-3.
Andrés A. Cancer incidence after immunosuppressive treatment following kidney transplantation. Crit Rev Oncol Hematol 2005;56:71-85.
Yunus M, Aziz T, Mubarak M. Posttransplant malignancies in renal transplant recipients: 22-years experience from a single center in Pakistan. Asian Pac J Cancer Prev 2012;13:575-8.
Ho WL, Murphy GM. Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients. Br J Dermatol 2008;158:217-24.
Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. J Am Acad Dermatol 2002;47:1-7.
Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 2012;166:1069-80.
Roy C, Gies H, Toomey S. The solar UV radiation environment: Measurement techniques and results. J Photochem Photobiol B 1995;31:21-7.
Gies H, Roy C, McLennan A, Tomlinson D, editors. Trends in ultraviolet radiation. Trends in Sun Protection Seminar Victoria. Australia: Anti Cancer Council of Victoria; 1999.
Glover MT, Bodmer J, Bodmer W, Kennedy LJ, Brown J, Navarrete C, et al.
HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer. Eur J Cancer 1993;29A: 520-4.
Czarnecki D, Zalcberg J, Kulinskáya E, Kay T. Impaired cell-mediated immunity of apparently normal patients who had multiple skin cancers. Cancer 1995;76:228-31.
Czarnecki DB, Lewis A, Nicholson I, Tait B. Multiple nonmelanoma skin cancer associated with HLA DR7 in Southern Australia. Cancer 1991;68:439-40.
Pakzad R, Soltani S, Salehiniya H. Epidemiology and trend in skin cancer mortality in Iran. J Res Med Sci 2015;20:921-2.
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