Dataset Information

TP53 rs1625895 is Related to Breast Cancer Incidence and Early Death in Iranian Population.

ABSTRACT: Breast cancer as the second most common cancer worldwide tend to be experienced by Iranian women 10 years earlier with a peak incidence at the premenopausal stage. Genetic mutations of TP53 tumor suppressor gene has been shown to be related to early onset of breast cancer. It has been shown already that rs1625895 polymorphic site is related to glioma as well as lung cancer. In this study, we have investigated the role of rs1625895 polymorphism in breast cancer incidence in Iranian women. DNA extraction of 86 breast cancer patients and 96 control individuals have been used for allele-specific primer-PCR and genotyping of allele A and allele G of the TP53 rs1625895. Genotypes frequencies have been shown that GG homozygosis as the most frequent genotype is a significant association with increased risk of breast cancer development in Iranian women (odds ratio?=?6, p?=?0.002). On the other hand and in comparison to allele G, allele A could cause early death of breast cancer patients by threefolds significantly (p?=?0.011). As a conclusion, we show that allele A is the minor allele in both breast cancer patients and also control individuals and major allele G, is related to the increased risk of breast cancer development in Iranian women.

SUBMITTER: Assad Samani L

PROVIDER: S-EPMC6801240 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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<i>TP53</i> rs1625895 is Related to Breast Cancer Incidence and Early Death in Iranian Population.

Assad Samani Leila L Javadirad Seyed-Morteza SM Parsafar Soha S Tabatabaeian Hossein H Ghaedi Kamran K Azadeh Mansoureh M

Indian journal of clinical biochemistry : IJCB 20180621 4

Breast cancer as the second most common cancer worldwide tend to be experienced by Iranian women 10 years earlier with a peak incidence at the premenopausal stage. Genetic mutations of <i>TP53</i> tumor suppressor gene has been shown to be related to early onset of breast cancer. It has been shown already that rs1625895 polymorphic site is related to glioma as well as lung cancer. In this study, we have investigated the role of rs1625895 polymorphism in breast cancer incidence in Iranian women. ...[more]

PMID: 31686737

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Project description:BACKGROUND The early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors. MATERIAL AND METHODS Based on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ?1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed. RESULTS A total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7-78.9%), 75.8% (75.1-76.4%), and 72.3% (71.6-72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5-75.4%), 73.5% (72.0-74.9%), and 68.6% (67.0-70.1%), respectively. CONCLUSIONS Nomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

Project description:BackgroundHeterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.MethodsWe searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.ResultsWe identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.ConclusionsAmong Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

Dataset Information

TP53 rs1625895 is Related to Breast Cancer Incidence and Early Death in Iranian Population.

Publications

<i>TP53</i> rs1625895 is Related to Breast Cancer Incidence and Early Death in Iranian Population.

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