The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors.
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ABSTRACT:
SUBMITTER: Czerwinska P
PROVIDER: S-EPMC8061774 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor ? receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. METHODS: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. RESULTS: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value <; 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the "More Powerful" Quasi-Likelihood Score Test did not provide any evidence for association (MQLS; p = 0.41). CONCLUSIONS: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.
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Project description:While internal migration is widely occurring in countries across the world and older people are more likely to be left behind by family members who out-migrated to other locations, little attention has been paid to the cognitive health of those people who have been left behind (PLB). Understanding how these demographic patterns relate to older persons' cognitive health may inform efforts to reduce the disease burden due to cognitive decline. Data came from the China Health and Nutrition Survey in 1997, 2000 and 2004. Participants aged 55 to 93 who participated in a cognitive function screening test (score range: 0-31) in two or more waves and provided information on family members' migration (n = 1,267) were included in the analysis. A mixed linear model was used to investigate the association between being left behind by any members who had not resided in the household for at least 6 months at baseline and cognitive function. Approximately 10% of the participants had been left behind by family members who migrated out of their communities. A significant interaction was observed in relation to cognitive function between being left behind and the number of years from the first test. Specifically, there was a less steep decline in cognitive function of PLB compared to people not left behind. This longitudinal study showed that PLB tended to have a higher cognitive function compared to those not left behind due to their relatively stable transition in cognitive function during the study period.
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Project description:ObjectivesOsteoporosis, a prevalent skeletal disorder characterized by reduced bone strength, is closely linked to the IGF system, crucial for skeletal metabolism. However, the precise nature of this relationship remains elusive. In this study, we employed Mendelian randomization (MR) to unravel the associations between genetically predicted serum IGF system member levels and osteoporosis.MethodsA two-sample MR approach was employed to investigate these causal associations based on two individual datasets. Predictions of 14 serum levels of IGF system members were made using 11,036,163 relevant Single Nucleotide Polymorphisms (SNPs) within a cohort of 4,301 individuals of European descent. Genetic association estimates for osteoporosis were derived from two publicly available GWAS consortia: the Finnish consortium from the FinnGen biobank, comprising 212,778 individuals of Finnish descent (3,203 cases and 209,575 controls), and the UK consortium from the UK Biobank, including 337,159 individuals of European descent (5,266 cases and 331,893 controls).ResultsAccording to the UK dataset, IGF-1 levels were associated with a reduced risk of osteoporosis, as indicated by the weighted median method (Odds Ratio [OR] = 0.998, 95% CI = 0.997-1.000, P = 0.032). Additionally, higher levels of IGFBP-3 were linked to a decreased risk of osteoporosis using the Inverse-Variance Weighted (IVW) method (OR = 0.999, 95% CI = 0.998-1.000, P = 0.019), and CTGF levels exhibited a negative association with osteoporosis, as determined by the weighted median method (OR = 0.998, 95% CI = 0.996-0.999, P = 0.004). In the FinnGen dataset, IGF-1 and IGFBP-3 were not identified to be associated with osteoporosis. While, IGF-LR1 levels displayed a negative association with osteoporosis, according to the MR-Egger method (OR = 0.886, 95% CI = 0.795-0.987, P = 0.036), while CYR61 was linked to an increased risk of osteoporosis based on both the weighted median and IVW methods (OR = 1.154, 95% CI = 1.009-1.319, P = 0.037, and OR = 1.115, 95% CI = 1.022-1.215, P = 0.014, respectively).ConclusionThis study provides compelling evidence that certain IGF family members play a role in the pathogenesis of osteoporosis between different datasets, indicating population specific causal effects between IGF family and osteoporosis. Although the results from both datasets demonstrated that IGF family involved in the pathogenesis of osteoporosis, but the responding key molecules might be various among different population. Subsequent research is warranted to evaluate the potential of these biomarkers as targets for osteoporosis prevention and treatment in specific population.
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Project description:Genomic instability is a hallmark of cancer cells which results in excessive DNA damage. To counteract this, cells have evolved a tightly regulated DNA damage response (DDR) to rapidly sense DNA damage and promote its repair whilst halting cell cycle progression. The DDR functions predominantly within the context of chromatin and requires the action of chromatin-binding proteins to coordinate the appropriate response. TRIM24, TRIM28, TRIM33 and TRIM66 make up the transcriptional intermediary factor 1 (TIF1) family of chromatin-binding proteins, a subfamily of the large tripartite motif (TRIM) family of E3 ligases. All four TIF1 proteins are aberrantly expressed across numerous cancer types, and increasing evidence suggests that TIF1 family members can function to maintain genome stability by mediating chromatin-based responses to DNA damage. This review provides an overview of the TIF1 family in cancer, focusing on their roles in DNA repair, chromatin regulation and cell cycle regulation.
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Project description:BACKGROUND:Cancer patients' symptom burden is commonly attributed to their cancer and treatment. Increasingly, cancer patients have many other chronic comorbid conditions. However, the degree to which these comorbid conditions may contribute to the patient-reported symptom burden is unclear. METHODS:This study explored the relations between the presence of comorbid conditions, the symptom experience and burden, and the perceived bother from cancer or comorbid conditions in 3106 cancer patients. The associations between the number of comorbidities (identified from current medications), the patient-reported symptom burden (the number of symptoms scored as ?7 on the 13-item MD Anderson Symptom Inventory physical scale), the patient-reported bother from comorbid conditions and from cancer (from "not at all" to "extremely"), and the clinician-reported difficulty in caring for patients' symptoms were examined. RESULTS:According to medication lists, 19% of the patients had at least 5 of 12 comorbid conditions. Approximately 39% rated at least 1 symptom as???7, and this proportion increased with an increasing number of comorbid conditions (48% with???5 comorbid conditions vs 36% with 1 comorbid condition). One-third of the patients reported moderate or worse bother, and this was significantly associated with an increased number of comorbid conditions (odds ratio [OR], 2.4) and an increased symptom burden (OR, 1.22). Clinician ratings of difficulty in managing patients' symptoms were significantly associated with bother from cancer (OR, 2.0), comorbid conditions (OR, 1.6), and symptom burden (OR, 1.1). CONCLUSIONS:Comorbidity is common in cancer patients and is associated with a greater symptom burden and clinician reports of difficulty in managing patients' symptoms. Greater attention to comorbid conditions is needed to optimize the symptom management of cancer patients with multimorbidity. Cancer 2017;123:3835-3842. © 2017 American Cancer Society.
| S-EPMC5610613 | biostudies-literature