Dataset Information

Combined effects of TGFB1 +869 T/C and +915 G/C polymorphisms on acute rejection risk in solid organ transplant recipients: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND: Transforming growth factor-beta 1(TGF-?1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-?1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive. METHODS: Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0. RESULTS: Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58-0.96, P heterogeneity ?= 0.238; IP/LP vs. HP: OR ?= 0.77, 95% CI, 0.61-0.98, P heterogeneity ?= 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR ?= 0.32, 95% CI, 0.14-0.73, P heterogeneity ?= 0.790; IP/LP vs. HP: OR ?= 0.41, 95% CI, 0.20-0.85, P heterogeneity ?= 0.320). CONCLUSIONS: The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft.

SUBMITTER: Ge YZ

PROVIDER: S-EPMC3976347 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Combined effects of TGFB1 +869 T/C and +915 G/C polymorphisms on acute rejection risk in solid organ transplant recipients: a systematic review and meta-analysis.

Ge Yu-Zheng YZ Wu Ran R Lu Tian-Ze TZ Jia Rui-Peng RP Li Ming-Hao MH Gao Xiao-Fei XF Jiang Xiao-Min XM Zhu Xian-Bo XB Li Liang-Peng LP Tan Si-Jia SJ Song Qun Q Li Wen-Cheng WC Zhu Jia-Geng JG

PloS one 20140404 4

<h4>Background</h4>Transforming growth factor-beta 1(TGF-β1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-β1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive.<h4>Methods</h4>Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and A ...[more]

PMID: 24705444

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Project description:BACKGROUND:Immunosuppressed solid organ transplant recipients [SOTRs] have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections. METHODS:We performed a cohort study of 262,455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs to the general population. We used Poisson regression to calculate incidence rate ratios (IRRs) according to immune-related SOTR characteristics, including time since transplant (i.e., duration of immunosuppression). All statistical tests are two-sided. RESULTS:We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni p?<?7.2 x 10-5). All 33 are rare (incidence <6 per 100,000 person-years) and several have known viral etiology (e.g. Merkel cell carcinoma (SIR = 24.7, 95%CI = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas (SCCs) of the lip (SIR range = 18.3-19.8), eye/adnexa (SIR = 13.8, 95%CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95%CI = 6.1 to 13.5), and nasal cavity/sinuses (SIR = 4.5, 95%CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95%CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (ptrend<0.05), including SCCs of the lip, salivary gland, and anogenital sites. CONCLUSIONS:SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.

Project description:ObjectiveTo examine the incidence of lower genital tract dysplasia in women after solid organ transplantation, to evaluate risk factors associated with development of dysplasia, and to assess the timeline of disease development.MethodsThis was a retrospective study of female patients who underwent solid organ transplantation at a large-volume tertiary care center between 2000 and 2015. Demographic and clinicopathologic factors were extracted from electronic medical records. Cumulative incidence of lower genital tract dysplasia was calculated, and univariate and multivariable logistic regression were performed to identify risk factors for the development of dysplasia.ResultsAmong 394 female solid organ transplant recipients, the median age was 41 years (interquartile range 29-53). Forty-seven (11.9%; 95% CI 8.8-15.9%) women developed lower genital tract dysplasia over a median follow-up of 7.8 years (interquartile range 4.6-12.9). Thirty-eight (9.6%) developed cervical intraepithelial neoplasia (CIN), with 14 (3.6%) diagnosed with CIN 2 or worse (one was cervical carcinoma). Nineteen (4.8%) developed noncervical lower genital tract dysplasia, including vulvar, vaginal, or anal dysplasia, with 13 (3.3%) diagnosed with high-grade dysplasia or worse (five were lower genital tract carcinoma [three anal, one vulvar, and one vaginal]). Ten (2.5%) developed both cervical and noncervical lower genital tract dysplasia. Black race was significantly associated with developing dysplasia (odds ratio [OR] 2.86; 95% CI 1.33-6.13) as was hydroxychloroquine use (OR 5.95; 95% CI 1.96-18.09). High-grade cervical dysplasia was diagnosed at a median interval of 3.18 years after transplant; noncervical high-grade lower genital tract dysplasia was diagnosed at a median interval of 3.94 years.ConclusionsOne in eight transplant recipients developed lower genital tract dysplasia and approximately half were high-grade dysplasia or cancer. Black race and hydroxychloroquine use were associated with an increased risk of dysplasia. Yearly cervical screening and comprehensive lower genital examination beyond the cervix is indicated in this population.

Dataset Information

Combined effects of TGFB1 +869 T/C and +915 G/C polymorphisms on acute rejection risk in solid organ transplant recipients: a systematic review and meta-analysis.

Publications

Combined effects of TGFB1 +869 T/C and +915 G/C polymorphisms on acute rejection risk in solid organ transplant recipients: a systematic review and meta-analysis.

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