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1.
Br J Dermatol ; 177(5): 1208-1216, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28994104

ABSTRACT

Keratinocyte carcinoma (KC) is the most common type of cancer among white populations, but it is even more common among solid organ transplant recipients (OTRs). The most frequent histological type of KC among OTRs is cutaneous squamous cell carcinoma (cSCC), followed by basal cell carcinoma, although the reverse is seen in the general population. Metastatic cSCCs are more frequent, and mortality is increased compared with immunocompetent populations. There is strong evidence that the risk of KC among OTRs rises with increasing time after transplantation and older age at transplantation, and that KC is enhanced in those with sun-damaged skin. This evidence suggests that accelerated accumulation of genetic damage from several sources leads to excess KC in OTRs. We describe international variation in KC and focus on trends in immunosuppressive regimens, the role of ultraviolet susceptibility and exposure, and the contribution of genetics to tumour development. Further epidemiological studies are needed to address gaps in our understanding of the mediation of excess KC by immunosuppressive drugs, viral infection, genetic susceptibility, timing of relevant ultraviolet exposure or some combination of these factors.


Subject(s)
Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Keratinocytes , Organ Transplantation/adverse effects , Skin Neoplasms/epidemiology , Humans , Immunosuppressive Agents/adverse effects , Transplant Recipients
2.
Br J Dermatol ; 177(5): 1202-1207, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28952162

ABSTRACT

Long-term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65-fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.


Subject(s)
Carcinoma, Basal Cell/prevention & control , Carcinoma, Squamous Cell/prevention & control , Keratinocytes , Organ Transplantation/adverse effects , Skin Neoplasms/prevention & control , Carcinoma, Basal Cell/etiology , Carcinoma, Squamous Cell/etiology , Early Detection of Cancer , Female , Humans , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/adverse effects , Male , Risk Assessment/methods , Risk Factors , Skin Neoplasms/etiology
3.
Am J Transplant ; 17(11): 2911-2921, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28397388

ABSTRACT

Solid organ transplant recipients have an elevated incidence of thyroid cancer. We evaluated a wide range of potential risk factors in a cohort of 229 300 U.S. solid organ transplant recipients linked with 15 stage/regional cancer registries (1987-2012). Incidence rate ratios (IRRs) were adjusted for age, sex, race/ethnicity, transplanted organ, year of transplantation, and time since transplantation. Hazard ratios (HRs) for death and/or graft failure were adjusted for age, sex, race/ethnicity, transplanted organ, and year of transplantation. After transplantation, 356 thyroid cancers were diagnosed. Thyroid cancer incidence was 2.50-fold higher in transplant recipients than the general population (95% confidence interval [CI] 2.25-2.77). Among recipients of different organs, kidney recipients had the highest incidence of thyroid cancer (IRR = 1.26, 95% CI 1.03-1.53). Elevated thyroid cancer incidence was associated with cholestatic liver disease/cirrhosis as an indication for liver transplantation (IRR = 1.69, 95% CI 1.09-2.63), hypertensive nephrosclerosis as an indication for kidney transplantation (IRR = 1.41, 95% CI 1.03-1.94), and longer prior dialysis among kidney recipients (5+ vs. <1 year, IRR = 1.92, 95% CI 1.32-2.80; p-trend <0.01). Posttransplantation diagnosis of thyroid cancer was associated with modestly increased risk of death (HR = 1.33, 95% CI 1.02-1.73). Overall, our results suggest that end-stage organ disease and longer duration of dialysis may contribute to higher thyroid cancer incidence in transplant recipients.


Subject(s)
Organ Transplantation/adverse effects , Renal Dialysis/statistics & numerical data , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/etiology , Adult , Age Factors , Aged , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Prognosis , Registries , Risk Factors , Transplant Recipients , United States/epidemiology
5.
Am J Transplant ; 16(12): 3479-3489, 2016 12.
Article in English | MEDLINE | ID: mdl-27160653

ABSTRACT

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987-2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27-6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p-trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.


Subject(s)
Carcinoma, Renal Cell/etiology , Graft Rejection/etiology , Kidney Neoplasms/etiology , Kidney Transplantation/adverse effects , Postoperative Complications , Adult , Carcinoma, Renal Cell/epidemiology , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/epidemiology , Humans , Incidence , Kidney Failure, Chronic/surgery , Kidney Function Tests , Kidney Neoplasms/epidemiology , Male , Middle Aged , Prognosis , Risk Factors , United States/epidemiology
6.
Am J Transplant ; 16(10): 2986-2993, 2016 10.
Article in English | MEDLINE | ID: mdl-27062091

ABSTRACT

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research.


Subject(s)
Data Collection/standards , Neoplasms/diagnosis , Organ Transplantation , Registries/standards , Adult , Female , Humans , Incidence , Male , Neoplasms/epidemiology , Prognosis , United States/epidemiology
7.
Am J Transplant ; 16(3): 960-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26731613

ABSTRACT

Solid organ transplant recipients have increased colorectal cancer (CRC) risk. We assessed CRC risk among transplant recipients and identified factors contributing to this association. The US transplant registry was linked to 15 population-based cancer registries (1987-2010). We compared CRC risk in recipients to the general population by using standardized incidence ratios (SIRs) and identified CRC risk factors by using Poisson regression. Based on 790 cases of CRC among 224 098 transplant recipients, the recipients had elevated CRC risk (SIR 1.12, 95% confidence interval [CI] 1.04 to 1.20). The increase was driven by an excess of proximal colon cancer (SIR 1.69, 95% CI 1.53 to 1.87), while distal colon cancer was not increased (SIR 0.93, 95% CI 0.80 to 1.07), and rectal cancer was reduced (SIR 0.64, 95% CI 0.54 to 0.76). In multivariate analyses, CRC was increased markedly in lung recipients with cystic fibrosis (incidence rate ratio [IRR] 12.3, 95% CI 6.94 to 21.9, vs. kidney recipients). Liver recipients with primary sclerosing cholangitis and inflammatory bowel disease also had elevated CRC risk (IRR 5.32, 95% CI 3.73 to 7.58). Maintenance therapy with cyclosporine and azathioprine was associated with proximal colon cancer (IRR 1.53, 95% CI 1.05 to 2.23). Incidence was not elevated in a subgroup of kidney recipients treated with tacrolimus and mycophenolate mofetil, pointing to the relevance of the identified risk factors. Transplant recipients have increased proximal colon cancer risk, likely related to underlying medical conditions (cystic fibrosis and primary sclerosing cholangitis) and specific immunosuppressive regimens.


Subject(s)
Colorectal Neoplasms/etiology , Graft Rejection/etiology , Organ Transplantation/adverse effects , Postoperative Complications , Registries , Adult , Aged , Colorectal Neoplasms/epidemiology , Female , Follow-Up Studies , Graft Survival , Humans , Incidence , Male , Middle Aged , Prognosis , Risk Assessment , Risk Factors , Transplant Recipients , United States/epidemiology
10.
Am J Transplant ; 15(1): 129-36, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25522018

ABSTRACT

Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Neoplasms/epidemiology , Sirolimus/therapeutic use , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/drug therapy , Humans , Incidence , Kidney Function Tests , Male , Middle Aged , Prognosis , Registries , Risk Assessment , United States/epidemiology
11.
Am J Transplant ; 14(6): 1376-82, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24712385

ABSTRACT

Transmission of cancer is a life-threatening complication of transplantation. Monitoring transplantation practice requires complete recording of donor cancers. The US Scientific Registry of Transplant Recipients (SRTR) captures cancers in deceased donors (beginning in 1994) and living donors (2004). We linked the SRTR (52,599 donors, 110,762 transplants) with state cancer registries. Cancer registries identified cancers in 519 donors: 373 deceased donors (0.9%) and 146 living donors (1.2%). Among deceased donors, 50.7% of cancers were brain tumors. Among living donors, 54.0% were diagnosed after donation; most were cancers common in the general population (e.g. breast, prostate). There were 1063 deceased donors with cancer diagnosed in the SRTR or cancer registry, and the SRTR lacked a cancer diagnosis for 107 (10.1%) of these. There were 103 living donors with cancer before or at donation, diagnosed in the SRTR or cancer registry, and the SRTR did not have a cancer diagnosis for 43 (41.7%) of these. The SRTR does not record cancers after donation in living donors and so missed 81 cancers documented in cancer registries. In conclusion, donor cancers are uncommon, but lack of documentation of some cases highlights a need for improved ascertainment and reporting by organ procurement organizations and transplant programs.


Subject(s)
Neoplasms/epidemiology , Registries , Tissue Donors , Humans , United States/epidemiology
12.
Leukemia ; 28(12): 2317-23, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24727673

ABSTRACT

Solid organ transplant recipients have elevated cancer risks, owing in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207 859 solid organ transplants (1987-2009). Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8-5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4-9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression P<0.05 for all comparisons). Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after transplantation, P=0.0163). Overall survival following AML/MDS among transplant recipients was inferior to that of similar patients reported to US cancer registries (log-rank P<0.0001). Our novel finding of increased risks for specific myeloid neoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients.


Subject(s)
Leukemia, Myeloid/epidemiology , Leukemia, Myeloid/etiology , Organ Transplantation/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Leukemia, Myeloid/diagnosis , Male , Middle Aged , Mortality , Registries , Risk , United States/epidemiology , Young Adult
13.
Br J Cancer ; 110(11): 2796-803, 2014 May 27.
Article in English | MEDLINE | ID: mdl-24691420

ABSTRACT

BACKGROUND: Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. METHODS: From the US SEER-Medicare database, 44,191 NHL, 1832 HL and 200,000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. RESULTS: Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15-28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24-1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28-1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001). CONCLUSIONS: Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.


Subject(s)
Lymphoma, B-Cell, Marginal Zone/etiology , Lymphoma, T-Cell/etiology , Respiratory Tract Infections/complications , Aged , Aged, 80 and over , Case-Control Studies , Cellulitis/complications , Female , Herpes Zoster/complications , Hodgkin Disease/virology , Humans , Male , Risk Factors , SEER Program
14.
Am J Transplant ; 13(12): 3202-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24119294

ABSTRACT

Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva and oropharynx. We examined the incidence of HPV-related cancers in 187 649 US recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRRs) compared rates across transplant subgroups. We observed elevated incidence of HPV-related cancers (SIRs: in situ 3.3-20.3, invasive 2.2-7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal and penile cancers (IRRs 2.1-4.6 for 5+ vs. <2 years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13 and increased incidence with B:44, contributed to susceptibility at several sites. Use of specific immunosuppressive medications was variably associated with incidence; for example, tacrolimus, was associated with reduced incidence for some anogenital cancers (IRRs 0.4-0.7) but increased incidence of oropharyngeal cancer (IRR 2.1). Thus, specific features associated with recipient characteristics, transplanted organs and medications are associated with incidence of HPV-related cancers after transplant. The absence of increased incidence of invasive cervical cancer highlights the success of cervical screening in this population and suggests a need for screening for other HPV-related cancers.


Subject(s)
Anus Neoplasms/complications , Immunosuppression Therapy/adverse effects , Organ Transplantation/adverse effects , Oropharyngeal Neoplasms/complications , Papillomavirus Infections/complications , Penile Neoplasms/complications , Uterine Cervical Neoplasms/complications , Vulvar Neoplasms/complications , Adolescent , Adult , Anus Neoplasms/epidemiology , Anus Neoplasms/virology , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Oropharyngeal Neoplasms/epidemiology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Penile Neoplasms/epidemiology , Penile Neoplasms/virology , Registries , Tacrolimus/adverse effects , United States/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology , Vulvar Neoplasms/epidemiology , Vulvar Neoplasms/virology , Young Adult
15.
Br J Cancer ; 109(1): 280-8, 2013 Jul 09.
Article in English | MEDLINE | ID: mdl-23756857

ABSTRACT

BACKGROUND: Solid organ transplant recipients have high risk of lymphomas, including non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). A gap in our understanding of post-transplant lymphomas involves the spectrum and associated risks of their many histologic subtypes. METHODS: We linked nationwide data on solid organ transplants from the US Scientific Registry of Transplant Recipients (1987-2008) to 14 state and regional cancer registries, yielding 791 281 person-years of follow-up for 19 distinct NHL subtypes and HL. We calculated standardised incidence ratios (SIRs) and used Poisson regression to compare SIRs by recipient age, transplanted organ, and time since transplantation. RESULTS: The risk varied widely across subtypes, with strong elevations (SIRs 10-100) for hepatosplenic T-cell lymphoma, Burkitt's lymphoma, NK/T-cell lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma (both systemic and primary cutaneous forms). Moderate elevations (SIRs 2-4) were observed for HL and lymphoplasmacytic, peripheral T-cell, and marginal zone lymphomas, but SIRs for indolent lymphoma subtypes were not elevated. Generally, SIRs were highest for younger recipients (<20 years) and those receiving organs other than kidneys. CONCLUSION: Transplant recipients experience markedly elevated risk of a distinct spectrum of lymphoma subtypes. These findings support the aetiologic relevance of immunosuppression for certain subtypes and underscore the importance of detailed haematopathologic workup for transplant recipients with suspected lymphoma.


Subject(s)
Lymphoma/epidemiology , Organ Transplantation/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Incidence , Infant , Male , Middle Aged , Registries , Risk Factors , Treatment Outcome , United States/epidemiology , Young Adult
16.
Am J Transplant ; 13(3): 714-20, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23331953

ABSTRACT

Transplant recipients have elevated cancer risk, but it is unknown if cancer risk differs across race and ethnicity as in the general population. US kidney recipients (N = 87,895) in the Transplant Cancer Match Study between 1992 and 2008 were evaluated for racial/ethnic differences in risk for six common cancers after transplantation. Compared to white recipients, black recipients had lower incidence of non-Hodgkin lymphoma (NHL) (adjusted incidence rate ratio [aIRR] 0.60, p<0.001) and higher incidence of kidney (aIRR 2.09, p<0.001) and prostate cancer (aIRR 2.14, p<0.001); Hispanic recipients had lower incidence of NHL (aIRR 0.64, p = 0.001), lung (aIRR 0.41, p < 0.001), breast (aIRR 0.53, p = 0.003) and prostate cancer (aIRR 0.72, p = 0.05). Colorectal cancer incidence was similar across groups. Standardized incidence ratios (SIRs) measured the effect of transplantation on cancer risk and were similar for most cancers (p≥0.1). However, black and Hispanic recipients had larger increases in kidney cancer risk with transplantation (SIRs: 8.96 in blacks, 5.95 in Hispanics vs. 4.44 in whites), and only blacks had elevated prostate cancer risk following transplantation (SIR: 1.21). Racial/ethnic differences in cancer risk after transplantation mirror general population patterns, except for kidney and prostate cancers where differences reflect the effects of end-stage renal disease or transplantation.


Subject(s)
Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Kidney Diseases/complications , Kidney Transplantation/adverse effects , Neoplasms/epidemiology , Neoplasms/etiology , White People/statistics & numerical data , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Kidney Diseases/surgery , Male , Middle Aged , Prognosis , Registries , Risk Factors , Young Adult
17.
Am J Transplant ; 12(5): 1268-74, 2012 May.
Article in English | MEDLINE | ID: mdl-22300426

ABSTRACT

Posttransplant lymphoproliferative disorder (PTLD) is a major complication of solid-organ transplantation. With human immunodeficiency virus infection (an analogous immunosuppressive state), elevated kappa and lambda immunoglobulin free light chains (FLCs) in peripheral blood are associated with increased risk of lymphoma. To assess the role of B-cell dysfunction in PTLD, we measured circulating FLCs among Canadian transplant recipients, including 29 individuals with PTLD and 57 matched transplant recipients who were PTLD-free. Compared with controls, PTLD cases had higher kappa FLCs (median 1.53 vs. 1.07 times upper limit of normal) and lambda FLCs (1.03 vs. 0.68). Using samples obtained on average 3.5 months before PTLD diagnosis, cases were more likely to have polyclonal FLC elevations (i.e. elevated kappa and/or lambda with normal kappa/lambda ratio: odds ratio [OR] 4.2, 95%CI 1.1-15) or monoclonal elevations (elevated kappa and/or lambda with abnormal ratio: OR 3.0, 95%CI 0.5-18). Strong FLC-PTLD associations were also observed at diagnosis/selection. Among recipients with Epstein-Barr virus (EBV) DNA measured in blood, EBV DNAemia was associated with FLC abnormalities (ORs 6.2 and 3.2 for monoclonal and polyclonal elevations). FLC elevations are common in transplant recipients and associated with heightened PTLD risk. FLCs likely reflect B-cell dysfunction, perhaps related to EBV-driven lymphoproliferation.


Subject(s)
Antibodies, Viral/blood , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Lymphoproliferative Disorders/etiology , Organ Transplantation/adverse effects , Adolescent , Adult , B-Lymphocytes/immunology , B-Lymphocytes/virology , Case-Control Studies , Child , Child, Preschool , DNA, Viral/genetics , Female , Herpesviridae/genetics , Herpesviridae Infections/complications , Herpesviridae Infections/virology , Humans , Immunocompromised Host , Infant , Lymphoproliferative Disorders/blood , Male , Middle Aged , Predictive Value of Tests , Prognosis , Young Adult
18.
Br J Cancer ; 103(1): 112-4, 2010 Jun 29.
Article in English | MEDLINE | ID: mdl-20551958

ABSTRACT

BACKGROUND: Immunosuppression is a risk factor for certain skin cancers. Autoimmune conditions can involve the skin, and may involve immunosuppressive therapies. METHODS: We conducted a population-based case-control study among elderly US adults using Surveillance, Epidemiology, and End Results-Medicare-linked data of 44,613 skin cancer cases and 178,452 frequency-matched controls. Medicare claims identified autoimmune conditions. Adjusted odds ratios (ORs) compared prevalence in cases and controls. RESULTS: The most frequent autoimmune condition was rheumatoid arthritis (2.29%), which was associated with slightly increased risk of Merkel cell carcinoma (N=1977; OR (95%CI): 1.39 (1.10-1.74)). Risk of cutaneous non-Hodgkin's lymphoma (N=2652) was increased with psoriasis (OR (95%CI): 3.20 (2.62-3.92)). Risk of Kaposi's sarcoma (N=773) was elevated with ulcerative colitis (OR (95%CI): 2.76 (1.42-5.39)), and risk of other sarcomas (N=1324) was elevated with Graves disease (2.62 (1.30-5.31)). CONCLUSIONS: These findings suggest that immune disturbances in the skin, arising from autoimmune conditions or their treatment, promote development of skin cancer.


Subject(s)
Autoimmune Diseases/complications , Skin Neoplasms/etiology , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Risk , Skin Neoplasms/immunology
19.
Br J Cancer ; 100(5): 822-8, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19259097

ABSTRACT

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies.


Subject(s)
Autoimmune Diseases/complications , Myelodysplastic Syndromes/etiology , Myelodysplastic-Myeloproliferative Diseases/etiology , Myeloproliferative Disorders/etiology , Aged , Aged, 80 and over , Autoimmune Diseases/epidemiology , Female , Humans , Male , Myelodysplastic Syndromes/epidemiology , Myelodysplastic-Myeloproliferative Diseases/epidemiology , Myeloproliferative Disorders/epidemiology , Odds Ratio , Risk Factors , Time Factors
20.
Br J Cancer ; 100(5): 817-21, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19190628

ABSTRACT

Systemic autoimmune rheumatic diseases (SARDs) are chronic inflammatory and immuno-modulatory conditions that have been suggested to affect cancer risk. Using the Surveillance, Epidemiology and End Results-Medicare-linked database, women aged 67-99 years and diagnosed with incident breast cancer in 1993-2002 (n=84 778) were compared with an equal number of age-matched cancer-free female controls. Diagnoses of SARDs, including rheumatoid arthritis (RA, n=5238), systemic lupus erythematosus (SLE, n=340), Sjogren's syndrome (n=374), systemic sclerosis (n=128), and dermatomyositis (n=31), were determined from claim files for individuals from age 65 years to 1 year before selection. Associations of SARD diagnoses with breast cancer, overall and by oestrogen receptor (ER) expression, were assessed using odds ratio (OR) estimates from multivariable logistic regression models. The women diagnosed with RA were less likely to develop breast cancer (OR=0.87, 95% confidence interval (CI)=0.82-0.93). The risk reduction did not differ by tumour ER-status (OR=0.83, 95% CI=0.78-0.89 for ER-positive vs OR=0.91, 95% CI=0.81-1.04 for ER-negative, P for heterogeneity=0.14). The breast cancer risk was not associated with any of the other SARDs, except for a risk reduction of ER-negative cases (OR=0.49, 95% CI=0.26-0.93) among women with SLE. These findings suggest that systemic inflammation may affect breast epithelial neoplasia.


Subject(s)
Aged , Autoimmune Diseases/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Rheumatic Diseases/epidemiology , Aged, 80 and over , Autoimmune Diseases/complications , Breast Neoplasms/metabolism , Case-Control Studies , Estrogen Receptor alpha/metabolism , Female , Humans , Odds Ratio , Population , Rheumatic Diseases/complications , Risk Factors , Social Class
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