Risk of neoplasia in renal transplant patients

London, N.J.M.; Farmery, Susan M.; Lodge, J.P.A.; Will, Eric J.; Davidson, Alexander M.

doi:10.1016/s0140-6736(95)92780-8

Cited by 358 publications

(214 citation statements)

References 8 publications

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“…This study emphasizes the need for frequent screening for skin tumours in transplant recipients, and this need for surveillance is recognized by other groups (Leigh and Glover, 1995;London et al, 1995). In particular, these data emphasize the clinical importance of screening for potentially lethal anogenital neoplasms in highsusceptibility RARs.…”

Section: Discussionsupporting

confidence: 62%

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy

Arends¹,

Benton²,

McLaren³

et al. 1997

Br J Cancer

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Section: Discussionsupporting

confidence: 62%

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy

Arends¹,

Benton²,

McLaren³

et al. 1997

Br J Cancer

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“…Similarly, rates of p53 mutation have been reported to be low in cervical cancers in which HPV was detected (compared with tumours in which virus was not detected) in some, but not all, studies of cervical carcinoma, the implication being that viral products may inactivate the p53 tumour-suppressor genes by alternative mechanisms to mutation (Crook et al, 1991;Busby-Earle et al, 1992;Vousden, 1993). Transplant recipients receiving immunosuppression show an elevated risk of various tumour types that have in common a possible viral pathogenesis, including lymphoma, cervix and Kaposi's sarcoma of the skin (Kinlen et al, 1979;London et al 1995). Given the increased risk of NMSC and the high prevalence of HPV infection, it is therefore tempting to imagine that HPV cause NMSC.…”

Section: Resultsmentioning

confidence: 99%

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

Rehman

Quinn²,

Takata³

et al. 1997

Br J Cancer

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Summary Organ transplant recipients receiving immunosuppression show a dramatically increased risk of non-melanoma skin cancer. The cause of this increase is not known. We report that the rate of loss of heterozygosity (at all the loci we examined) was significantly lower in tumours from immunosuppressed individuals than in tumours from immunocompetent subjects [20 out of 148 (14%) vs 157 out of 428 (37%); P < 0.0001]. These results suggest that tumours in immunosuppressed individuals have a different molecular pathogenesis.Keywords: loss of heterozygosity; non-melanoma skin cancer; immunosuppression; tumour suppressor; human papilloma virus; squamous cell carcinoma Patients receiving immunosuppressive therapy after organ transplantation show up to a 250-fold increase in the incidence of nonmelanoma skin cancers (NMSCs) and their precursor lesions (Abel, 1989; Hartevelt et al, 1990; Espana et al, 1995; Glover et al, 1997). In such patients the high prevalence of infection by a spectrum of human papilloma virus (HPV) types together with a high incidence of other neoplasms associated with a viral pathogenesis has suggested a role for virus during NMSC development (Barr et al, 1989). However, in skin, unlike cervical carcinoma, compelling evidence that HPVs play a causative role, rather than being mere passengers, is lacking. It is also possible that other viruses such as the recently described Kaposi's sarcoma herpes-like virus (KSHV) (Boshoff et al, 1996) or as yet unidentified viruses may be important. We therefore sought indirect evidence for a different molecular pathogenesis in these tumours that would provide support for a causal role for one or more types of virus, including viruses that had not yet been identified.Tumour-suppressor gene inactivation commonly occurs by mutation of one allele accompanied by chromosome loss of the wild-type allele (Knudson, 1991). Other mechanisms of tumoursuppressor gene activation can occur, including binding of the products of virally encoded oncogenes or changes in methylation status of tumour-suppressor genes (Vousden, 1993;Kinzler and Vogelstein, 1996). If, in tumours from immunosuppressed individuals, tumour-suppressor genes are being inactivated by alternative means, then the rate or pattern of loss of heterozygosity might be expected to differ from those in immunocompetent individuals. We examined this hypothesis. Ten-micrometre tissue sections were carefully microdissected to separate tumour from adjacent normal epithelium, and the DNA was extracted using phenol-chloroform (Jackson et al, 1995). In all cases, control DNA from either adjacent normal skin or blood was used. Tumour and control DNA was subject to polymerase chain reaction (PCR) amplification using one [y-32P]ATP (Life Sciences, Amersham, UK) end-labelled primer as previously described (Rehman et al, 1996), using microsatellite markers 3p (D3S1293), 9p (D9S162, D9S171), 9q (D9S197), 13q (D13S170), 17p (D17S796) and 17q (D17S785) (Research Genetics, Huntsville, AL, USA). PCR products were resolved on a ...

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“…A number of European studies report a 27 ± 40% cumulative risk of developing either a basal cell (BCC) or squamous cell cancer (SCC) within the ®rst 20 years following transplantation (Hartevelte et al, 1990;London et al, 1995;McGregor and Proby, 1995). Several mechanisms have been suggested to account for this increase, including chemical carcinogenesis (Lennard et al, 1985;Swann et al, 1996), altered DNA repair (Kelly et al, 1987;Swann et al, 1996) and loss of immune surveillance (Doll and Kinlen, 19970).…”

mentioning

confidence: 99%

“…In addition, however, a considerable body of epidemiological evidence is consistent with an association between sun exposure and skin cancer in transplant recipients. The cumulative incidence of skin cancer following transplantation in sub-tropical regions of Australia is considerably higher than in patients transplanted and resident in Europe and furthermore, over 90% of transplant skin cancers occur on sun-exposed sites (Hartevelt et al, 1990;London et al, 1995;McGregor and Proby, 1995;Bouwes Bavinck et al, 1996). The data we present in this study provide molecular evidence consistent with a causal role for sun exposure in the development of post-transplant skin cancer.…”

mentioning

confidence: 99%

p53 mutations implicate sunlight in post-transplant skin cancer irrespective of human papillomarivus status

et al. 1997

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Mutations in p53 were detected in 11/23 (48%) of non melanoma skin cancers in renal allograft recipients and in 5/8 (63%) of sporadic tumours from immune competent patients. 9/12 (75%) of mutations in transplant patients and all 5 mutations in non transplant tumours were consistent with damage caused by ultraviolet (u.v.) irradiation. DNA sequences, predominantly of the epidermodysplasia verruciformis (EV) subgroup, were detected in 9/23 (39%) of transplant tumours and in 2/8 (25%) of eight non-transplant tumours. There was no relationship between HPV status and p53 mutation, HPV DNA being present in 5/16 (31%) of tumours with p53 mutation and 6/15 (40%) of tumours lacking p53 mutation. These data are consistent with an important role for sunlight in the development of post-transplant skin cancer, and with limited functional data suggesting that E6 proteins of the cutaneous and EV-related papillomaviruses do not target p53 for ubiquitin-mediated degradation.

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Risk of neoplasia in renal transplant patients

Cited by 358 publications

References 8 publications

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

p53 mutations implicate sunlight in post-transplant skin cancer irrespective of human papillomarivus status

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