BC-DETECT: combined detection of serum HE4 and TFF3 improves breast cancer diagnostic efficacy.

BACKGROUND: Early accurate breast cancer (BC) diagnosis is critical in disease management. Mammography has been widely used. However, its radiation, and high false-negative and -positive results have always been a concern. We evaluated combined detection of human epididymal protein 4 (HE4) and trefoil factor 3 (TFF3) as substitute method to enhance BC diagnosis. METHODS: HE4 and TFF3 blood levels were determined by ELISA in sera of 120 BC patients and 80 women (40 healthy and 40 benign breast disease) as controls. Receiver-operating characteristic curve was applied for evaluation diagnostic power of each biomarker and their combination. RESULTS: In BC patients, serum HE4 [5 (2-11.9) vs. 3.1 (1.8-5.4) and 1 (1-3.5); P = 0.022] and TFF3 [5.3 (4.5-6.7) vs. 4.7 (4-4.8) and 3.9 (3-4.4); P = 0.027] were significantly higher than that in benign and healthy groups, respectively. Both HE4 (AUC = 0.783; P < 0.0001) and TFF3 (AUC = 0.759; P < 0.0001) had superior BC diagnostic ability compared to CEA and CA-15.3. Logistic regression analysis revealed simplified index BC-DETECT = HE4 + TFF3, and its values were significantly (P = 0.0132) elevated in BC (10.9 (8.4-17.2) compared to benign (7.2 (5.4-10.1)) and healthy (5.1 (4-6.3)) controls. AUC of BC-DETECT for BC prediction was (AUC = 0.850; P < 0.0001) with sensitivity, specificity, and positive and negative predictive values and accuracy of 84.2%, 70%, 80.8%, 74.7%, and 78.5%, respectively. High BC-DETECT levels were associated with tumor non-luminal subtypes, late stage, high grade, large size, lymph-node invasion, and multiple lesions. CONCLUSIONS: BC-DETECT is inexpensive, rapid, and easy to perform and reliably guides BC early detection. Moreover, the association between elevated BC-DETECT values and disease severity may propose its potential role as prognostic marker.

Genetic variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma.

The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma (HCC). The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of HCC and to identify the computational bioinformatics frameworks of these missense variants. A total of 250 participants were enrolled in this study, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method. The frequency of the APEX1 (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (p > .05). Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC.

Association of Apolipoprotein E gene polymorphism with the risk of T2DM and obesity among Egyptian subjects.

BACKGROUND: Numerous reports investigated the involvement of apolipoprotein E (APOE) polymorphisms with elevated risk of type 2 diabetes mellitus (T2DM) and obesity. The principal objective of this study is to assess the contribution of APOE polymorphisms (rs429358 and rs7412) with the risk of T2DM and obesity. SUBJECTS AND METHODS: This work was designed involving 400 participants [100 healthy controls, 100 T2DM patients, 100 obese patients, and 100 T2DM + obese patients]. Genomic deoxyribonucleic acid (DNA) of the APOE polymorphisms was characterized using the PCR-RFLP assay. RESULTS: The common predominant genotype of the study population is the APOE Ɛ3/Ɛ3 [T2DM patients (46%), obese patients (52%), T2DM + obese patients (37%), and healthy controls (58%)]. The frequencies of the APOE Ɛ4/Ɛ4 genotype and the APOE*Ɛ4 allele were significantly elevated among T2DM patients (p-value < 0.05). Additionally, the frequencies of the APOE Ɛ2/Ɛ2 genotype and the APOE*Ɛ2 allele were significantly increased among obese patients (p-value < 0.05). Moreover, the frequencies of the APOE Ɛ2/Ɛ2 genotype, APOE*Ɛ2 allele, APOE Ɛ4/Ɛ4 genotype, and APOE*Ɛ4 allele were statistically significant among T2DM + obese patients (p-value < 0.05). CONCLUSIONS: APOE*Ɛ2 and APOE*Ɛ4 alleles were considered as independent risk factor among T2DM + obese patients. Furthermore, the APOE*Ɛ2 allele was correlated with elevated risk of obesity, while the APOE*Ɛ4 allele was correlated with elevated risk of T2DM.

Leptin gene tetranucleotide repeat polymorphism in obese individuals in Egypt.

BACKGROUND: Leptin is a peptide hormone secreted by the adipose tissue. Genetic mutations of the leptin gene were reported to cause severe obesity. OBJECTIVES: This study was undertaken to investigate the association of the polymorphic tetranucleotide repeat locus 3' UTR of leptin gene with obesity in Egyptian cases. SUBJECTS AND METHODS: This study has included 120 subjects affected with obesity 57 of them were consistent with the diagnosis of metabolic syndrome (MS) while the rest (63) had simple obesity. These cases were compared to 83 normal weight healthy controls. All participants were subjected to an estimation of their body mass index (BMI), waist hip ratio (WHR), serum as well as characterization of leptin gene tetranucleotide repeat (TTTC)n polymorphism by PCR technique. RESULTS: Thirteen different alleles were identified in all cases of obesity versus only 5 alleles in normal controls. The most frequent allele was the 154 bp allele (57.5% in all cases of obesity vs. 92.2% in controls). Total cases with obesity showed a significantly higher carriage rate of class II alleles (I/II + II/II genotypes) compared to healthy controls (48.3% vs. 6.0%, OR=14.6, 95% CI=5.5-38.6, p=<0.0001). This was more apparent in the group with simple obesity (52.3% vs. 6.0%, OR=17.2, 95% CI=6.1-48.1, p=<0.0001) than in MS cases (43.9 % vs. 6.0 %, OR =12.19, 95% CI=4.9-30.4, p=< 0.0001). Interestingly, cases with MS did not differ from those with simple obesity regarding their class I or II allele frequencies (p> 0.05). Although serum lipids were significantly higher in obese cases compared to controls, no difference was found among obese cases with different leptin gene class genotypes (p> 0.05). CONCLUSIONS: Tetranucleotide repeat (TTTC)n polymorphism in the 3' UTR of the human leptin gene was associated with obesity in Egyptian obese cases showing higher class II allele carriage rate. However, the lipoprotein levels were not affected by this polymorphism.

Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian women with unexplained recurrent pregnancy loss.

AIMS: This work aims at testing for the association of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with unexplained recurrent pregnancy loss (RPL) among Egyptian women. SUBJECTS AND METHODS: Participants were 70 cases having a history of two or more events of unexplained RPL and 136 controls with a good obstetric history. Detection of MTHFR C677T and A1298C mutations was done by polymerase chain reaction with restriction fragment length polymorphisms assay using restriction enzymes HinfI and MboII respectively. RESULTS: Compared with controls, cases with unexplained pregnancy loss showed higher frequency of the homozygous mutant MTHFR 677 TT, 1298 CC genotypes, and the mutant haplotype 677T/1298C, although not reaching statistical significance. The frequency of 677 mutant genotypes (TT or TC) combined with either the mutant 1298 (CC or AC) or normal 1298 (AA) genotypes was significantly increased among cases with late-stage pregnancy loss versus those with early-stage pregnancy loss (p=0.001). There was also increased frequency of the 677 mutant genotypes among cases with secondary infertility compared with those with primary infertility and among cases with pregnancy loss >4 times compared with those with ≤4 times but with no statistical significance. Regarding other risk factors, it was noted that the frequency of mutations among cases with no or just one risk factor did not differ significantly from those having two or more risk factors (p=0.98). CONCLUSIONS: Mutations related to the MTHFR gene are increased but not statistically significant in Egyptian women with unexplained pregnancy loss. Interaction with other genetic variants might be speculated and need to be investigated.

Factor V Leiden and prothrombin gene mutations in Egyptian cases with unexplained recurrent pregnancy loss.

BACKGROUND: Thrombophilias have been suggested as a possible cause of recurrent pregnancy loss (RPL). OBJECTIVE: Testing for the association of factor V Leiden (FVL) and prothrombin (FII) mutations with RPL among cases from the Nile Delta region of Egypt. SUBJECTS AND METHODS: Participants included 72 cases having a history of two or more events of unexplained RPL and 70 controls with a good obstetric history. Detection of FVL (G1691A) and FII (G20210A) mutations was carried out using PCR with sequence specific primers. RESULTS: Cases showed a significantly higher frequency of FVL GA (OR = 21·38, P<0·0001) and FII GA (OR = 36·7, P<0·0001) genotypes. Cases with two or more risk factors had significant higher frequency of both mutant genotypes, while no significant difference could be elicited related to primary or secondary infertility, number of fetal losses, or phase of pregnancy loss. CONCLUSION: Screening for thrombophilic mutations may help in the prevention of unexplained RPL.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Egyptian patients with myocardial infarction.

INTRODUCTION: This work aimed to test the association of the angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism with myocardial infarction. SUBJECTS AND METHODS: This study comprised 79 Egyptian myocardial infarction cases with a mean age of 54.4+/-9.9 years including 60 males and 19 females, plus 238 healthy unrelated individuals of nearly matched age and sex as a control group. For all subjects, DNA testing for the angiotensin-converting enzyme gene I/D polymorphism was done using PCR amplification for detection of both the D and I alleles followed by a second run PCR specific for the I allele for samples typed as DD in the first run. RESULTS: Cases had a higher frequency of DD (29.1%) and ID (62.0%) genotypes than II (8.9%) genotype, with a higher frequency of D allele than I allele (64.4% vs. 33.6%). Compared to controls, cases had a significantly higher frequency of ID genotype (62.0% vs. 47.5%, p<0.05).This was more apparent among cases in the low risk group (p=0.002) than in the high risk group (p=0.041). CONCLUSION: The angiotensin-converting enzyme gene I/D polymorphism is probably a risk factor for ischaemic heart disease among Egyptian cases, particularly if integrated with other environmental and genetic risk factors.