Cancer Risk Triples After Kidney Grafts

SYDNEY, Australia, Dec. 19 -- Kidney transplantation is associated with a significant increase in the risk of cancer, including a tripling of the risk for cancer at 18 sites, researchers here reported.

A study of 28,855 end-stage renal disease patients who received kidney transplants found a slight but significant (P=0.002), increase in risk of cancer during dialysis (standardized incidence ratio 1.35; 95% CI, 1.27-1.45), but after transplant the SIR increased to 3.27 (95% CI, 3.09-3.46, P for trend <0.001).

Moreover, most of these cancers are those with known or suspected viral causes, reported epidemiologist Claire M.Vajdec, Ph.D., of the University of New South Wales, in the Dec. 20 issue of the Journal of the American Medical Association.

Following transplantation, there was a significant increase in risk of cancer at 25 sites, she said.

Immune suppression after transplantation is recognized as a risk factor for non-melanoma skin cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, but Dr. Vajdic and colleagues said it had been assumed that there was no increase in other cancers.

However, that issue had never been studied in a large population with long-term follow-up. The patients in this study had accumulated 273,407 person-years of follow-up.

Incident cancers were identified by linkage of the Australia and New Zealand Dialysis and Transplant Registry with the Australian National Cancer Statistics Clearing House.

Excluding non-melanoma skin cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, there were 1,236 observed cancers in patients who received kidney transplants, a population in which the number of expected cancer cases was 378.

In some cases the increases were especially striking. For example, there were 283 cancers of the lip versus six expected cases, 102 cancers of the lung, trachea, or bronchus versus the expected 42, and 111 melanomas compared with 44 expected.

Of 18 cancer sites with more than a threefold increase in risk five were at sites that are known to be caused by human papilloma virus (tongue, mouth , vulva, vagina, penis) and an additional four were at sites for which the evidence for human papillomavirus is limited or inconclusive (eye, salivary gland, esophagus, nasal cavity), they wrote.

Additionally, two cancer sites were known to be causally related to Epstein-Barr virus (Hodgkin's disease, non-Hodgkin's lymphoma), one was of a type known to be related to hepatitis B or hepatitis C virus (liver cancer), and the other was caused by human herpesvirus 8 (Kaposi's sarcoma), they continued.

There were an additional even cancer types that were significantly increased, but less than threefold, after transplantation. Among these, two are known to be human papillomavirus-related (cervical and anal cancer), and there is inconclusive evidence of a role for human papillomavirus in three others (stomach, colon, and lung cancer). There is no evidence for an infective agent causing melanoma or the majority of cases of leukemia

Interestingly, there was no post-transplantation excess risk for breast or prostate cancer, which are the two most common cancers among Australians and identified by screening methods. This suggested that the increased detection of cancer in the group was not related to increased surveillance.

Among the study's limitations was the need to retrospectively define the period before transplantation, which may have underestimated the incidence of cancer because some patients may not have been referred for transplant because of their cancer history.

The heightened cancer surveillance in the transplant population may also have introduced bias, they wrote.

The study was funded by the Cancer Council New South Wales.

Jeremy R. Chapman, M.D., a co-author, reported serving on advisory board and speaker panels for Astellas, Novartis, Wyeth, and Hoffmann la Roche as well as receiving research support from the National Health and Medical Research Council, Juvenile Diabetes Foundation International, Novartis, Wyeth, Jannsen-Cilag, and Hoffmann la Roche. Andrew E. Grulish, Ph.D., reported serving on the advisory board for the Gardasil human papillomavirus vaccine for Commonwealth Serum Laboratories.