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Risk of hepatobiliary cancer after solid organ transplant in the United States.

ABSTRACT: BACKGROUND & AIMS:Studies of liver cancer risk in recipients of solid organ transplants generally have been small, yielding mixed results, and little is known about biliary tract cancers among transplant recipients. METHODS:We identified incident hepatobiliary cancers among 201,549 US recipients of solid organs, from 1987 through 2008, by linking data from the US transplant registry with 15 cancer registries. We calculated standardized incidence ratios (SIRs), comparing risk relative to the general population. We also calculated incidence rate ratios (RRs), comparing risk for hepatocellular carcinoma (HCC) and total (intrahepatic and extrahepatic) cholangiocarcinoma among subgroups of recipients. RESULTS:Of transplant recipients, 165 developed hepatobiliary cancers (SIR, 1.2; 95% confidence interval [CI], 1.0-1.4). HCC risk was increased among liver recipients (SIR, 1.5; 95% CI, 1.0-2.2), especially 5 or more years after transplant (SIR, 1.8; 95% CI, 1.0-3.0). Cholangiocarcinoma was increased among liver (SIR, 2.9; 95% CI, 1.6-4.8) and kidney recipients (SIR, 2.1; 95% CI, 1.3-3.1). HCC was associated with hepatitis B virus (RR, 3.2; 95% CI, 1.3-6.9), hepatitis C virus (RR, 10; 95% CI, 5.9-16.9), and non-insulin-dependent diabetes (RR, 2.5; 95% CI, 1.2-4.8). Cholangiocarcinoma was associated with azathioprine maintenance therapy (RR, 2.0; 95% CI, 1.1-3.7). Among liver recipients, primary sclerosing cholangitis was associated with an increased risk of cholangiocarcinoma, compared with the general population (SIR, 21; 95% CI, 8.2-42) and compared with liver recipients without primary sclerosing cholangitis (RR, 12.3; 95% CI, 4.1-36.4). CONCLUSIONS:Risks for liver and biliary tract cancer are increased among organ transplant recipients. Risk factors for these cancers include medical conditions and potentially medications taken by recipients.

SUBMITTER: Koshiol J

PROVIDER: S-EPMC4064001 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Risk of hepatobiliary cancer after solid organ transplant in the United States.

Koshiol Jill J Pawlish Karen K Goodman Marc T MT McGlynn Katherine A KA Engels Eric A EA

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20131219 9

<h4>Background & aims</h4>Studies of liver cancer risk in recipients of solid organ transplants generally have been small, yielding mixed results, and little is known about biliary tract cancers among transplant recipients.<h4>Methods</h4>We identified incident hepatobiliary cancers among 201,549 US recipients of solid organs, from 1987 through 2008, by linking data from the US transplant registry with 15 cancer registries. We calculated standardized incidence ratios (SIRs), comparing risk relat ...[more]

PMID: 24362053

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Project description:BackgroundCytomegalovirus (CMV) is among the most common viral infections after solid organ transplantation (SOT). Associations of CMV with cancer risk among SOT recipients have been incompletely evaluated.MethodsThe authors used linked data from the US SOT registry and 32 cancer registries. Poisson regression was used to compare cancer incidence across CMV risk groups based on donor (D) and recipient (R) immunoglobulin G (IgG) serostatus: high risk (R-negative/D-positive), moderate risk (R-positive), and low risk (R-negative/D-negative).ResultsIn total, 247,318 SOT recipients were evaluated during 2000-2017 (R-negative/D-positive, 20.3%; R-positive, 62.9%; R-negative/D-negative, 16.8%). CMV-seropositive recipients were older, more racially/ethnically diverse, and had lower socioeconomic status than CMV-seronegative recipients. Compared with R-negative/D-negative recipients, recipients in the R-negative/D-positive and R-positive groups had a lower incidence of diffuse large B-cell lymphoma (DLBCL; R-negative/D-positive: adjusted incidence rate ratio [aIRR], 0.74; 95% confidence interval [CI], 0.59-0.91; R-positive: aIRR, 0.83; 95% CI, 0.69-1.00). CMV serostatus modified the association between Epstein-Barr virus (EBV) status and DLBCL (p = .0006): DLBCL incidence was increased for EBV R-negative/D-positive recipients (aIRR, 3.46; 95% CI, 1.50-7.95) among CMV R-negative/D-negative recipients but not among the other CMV risk groups. Compared with recipients who were CMV R-negative/D-negative, those who were R-negative/D-positive had a lower incidence of small intestine cancer (aIRR, 0.23; 95% CI, 0.09-0.63), and R-positive recipients had a higher incidence of lung cancer (aIRR, 1.24; 95% CI, 1.05-1.46). CMV status was not associated with risk for other cancers.ConclusionsCMV status was not associated with risk for most cancers among SOT recipients. The inverse association with DLBCL may reflect the protective effects of CMV prophylaxis or treatment with off-target efficacy against EBV infection (the major cause of lymphoma in SOT recipients).

Project description:BACKGROUND:Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors' knowledge no study to date has comprehensively examined associations between transplantation status and mortality after a cancer diagnosis. METHODS:The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987-2014). Cox models were used to examine the association between transplantation status and cancer-specific mortality, adjusting for demographic characteristics and cancer stage. RESULTS:For the majority of cancers, cancer-specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [95% CI], 2.18-3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61-2.19), bladder (aHR, 1.85; 95% CI, 1.58-2.17), and colorectum (aHR, 1.77; 95% CI, 1.60-1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B-cell lymphoma (aHR range, 1.21-1.47). Associations remained significant after adjustment for first-course cancer treatment and generally were stronger among patients with local-stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94-4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07-3.70), breast (aHR, 2.08; 95% CI, 1.50-2.88), and prostate (aHR, 1.60; 95% CI, 1.12-2.29), despite the lack of an association for prostate cancer overall. CONCLUSIONS:For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.

Project description:BackgroundSolid organ transplant recipients have an elevated risk of cancer. Quantifying deaths attributable to cancer can inform priorities to reduce cancer burden.MethodsLinked transplantation and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987-2014). Population-attributable fractions (PAFs) of deaths due to cancer and corresponding cancer-attributable mortality rates were estimated using Cox models.ResultsAmong 221,962 solid organ transplant recipients, 15,012 developed cancer. Approximately 13% of deaths (PAF, 13.2%) were attributable to cancer, corresponding to a cancer-attributable mortality rate of 516 per 100,000 person-years. Lung cancer was the largest contributor to mortality (PAF, 3.1%), followed by non-Hodgkin lymphoma (NHL; PAF, 1.9%), colorectal cancer (PAF, 0.7%), and kidney cancer (PAF, 0.5%). Cancer-attributable mortality rates increased with age at transplantation, reaching 1229 per 100,000 person-years among recipients aged ≥65 years. NHL was the largest contributor among children (PAF, 4.1%) and lung cancer was the largest contributor among recipients aged ≥50 years (PAFs, 3.7%-4.3%). Heart recipients had the highest PAF (16.4%), but lung recipients had the highest cancer-attributable mortality rate (1241 per 100,000 person-years). Overall, mortality attributable to cancer increased steadily with longer time since transplantation, reaching 15.7% of deaths (810 per 100,000 person-years) at ≥10 years after transplantation. Comparison of cancer-attributable mortality rates with specified causes of death indicated that some deaths recorded as other causes might instead be caused by cancer or its treatment.ConclusionsCancer is a substantial cause of mortality among solid organ transplant recipients, with major contributions reported from lung cancer and NHL. Cancer-attributable mortality increases with age and time since transplantation, and therefore cancer deaths will become an increasing burden as recipients live longer.

Project description:ImportanceRisk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights.ObjectiveTo assess SC incidence and patient survival after solid organ transplantation.Design, setting, and participantsThis cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals.Main outcomes and measuresSebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population.ResultsA total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P < .001), race/ethnicity (non-Hispanic Black vs non-Hispanic White, IRR, 0.28; 95% CI, 0.10-0.77; P = .01), older age (IRR, 7.85; 95% CI, 3.85-16.0; ≥65 vs 0-44 years; P < .001 for trend), use of thymoglobulin induction (IRR, 1.82; 95% CI, 1.16-2.86; P = .009), posttransplant cutaneous squamous cell carcinoma (IRR, 4.60; 95% CI, 2.67-7.94; P < .001), and longer time since transplant (IRR, 8.40; 95% CI, 3.94-17.90; ≥10 vs 0-1.9 years; P < .001 for trend). Muir-Torre syndrome-associated cancers were rare among both SOTRs and others with SC (3.3%-4.1%). Among patients with SC, prior transplantation was associated with increased overall mortality (adjusted hazard ratio, 2.09; 95% CI, 1.45-3.01), although few deaths were attributed to SC (4 of 92 SOTRs [4.3%]; 235 of 3585 non-SOTRs [6.6%]).Conclusions and relevanceAmong SOTRs, results of this large cohort study suggest that SC was associated with measures of immunosuppression, and overall survival was worse than for other patients with SC. Findings also suggest a possible role for UV radiation in carcinogenesis.

Dataset Information

Risk of hepatobiliary cancer after solid organ transplant in the United States.

Publications

Risk of hepatobiliary cancer after solid organ transplant in the United States.

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