Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.

PURPOSE: Cyclophosphamide, Epirubicin/Doxorubicin, 5-fluorouracil (CEF or CAF) chemotherapy has long been a standard first-line treatment for breast cancer. The genetic variations of enzymes that are responsible for the metabolism of these drugs have been linked to altered treatment response and toxicity. Two drug-metabolizing enzymes ALDH1A1 and NQO1 are critically involved in the pathways of CEF/CAF metabolism. This study aimed to evaluate the effect of ALDH1A1 (rs13959) and NQO1 (rs1800566) polymorphisms on treatment response and toxicities caused by adjuvant (ACT) and neoadjuvant chemotherapy (NACT) where CEF/CAF combination was used to treat Bangladeshi breast cancer patients. METHODS: A total of 330 patients were recruited from various hospitals, with 150 receiving neoadjuvant chemotherapy and 180 receiving adjuvant chemotherapy. To extract genomic DNA, a non-enzymatic simple salting out approach was adopted. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect genetic polymorphisms. Unconditional logistic regression was used to derive odds ratios (ORs) with 95% confidence intervals (CIs) to study the association between genetic polymorphisms and clinical outcome and toxicity. RESULTS: A statistically significant association was observed between ALDH1A1 (rs13959) polymorphism and treatment response (TT vs. CC: aOR = 6.40, p = 0.007; recessive model: aOR = 6.38, p = 0.002; allele model: p = 0.032). Patients with the genotypes TT and CT + TT of the NQO1 (rs1800566) polymorphism had a significantly higher risk of toxicities such as anemia (aOR = 0.34, p = 0.006 and aOR = 0.58, p = 0.021), neutropenia (aOR = 0.42, p = 0.044 and aOR = 0.57, p = 0.027), leukopenia (aOR = 0.33, p = 0.010 and aOR = 0.46, p = 0.005), and gastrointestinal toxicity (aOR = 0.30, p = 0.02 and aOR = 0.38, p = 0.006) when compared to the wild CC genotype, while patients with the genotype CT had a significant association with gastrointestinal toxicity (aOR = 0.42, p = 0.02) and leukopenia (aOR = 0.52, p = 0.010). The TT and CT + TT genotypes of rs13959 had a significantly higher risk of anemia (aOR = 2.00, p = 0.037 and aOR = 1.68, p = 0.029). There was no significant association between rs1800566 polymorphism and treatment response. CONCLUSION: Polymorphisms in ALDH1A1 (rs13959) and NQO1 (rs1800566) may be useful in predicting the probability of treatment response and adverse effects from CEF or CAF-based chemotherapy in breast cancer patients.

Response of Bangladesh to the World Health Organization call to eliminate cervical cancer as a public health issue: An observational report.

Background: Despite being preventable, cervical cancer remains a leading cause of mortality among Bangladeshi women. This article addresses the trends in Bangladesh's response to the World Health Organization's (WHO) request for the eradication of cervical cancer within the nation. Discussion: When it comes to cervical cancer, healthcare institutions need to be concerned in terms of protocols for diagnosis and treatment, staff education, and available resources. More than a quarter of all female cancers in Bangladesh are caused by cervical cancer, which can be prevented through better healthcare infrastructure, earlier diagnosis, more qualified healthcare professionals, improved urban and rural hospital infrastructure, community-based clinics, expanded affordable vaccinations, school-based delivery systems, adoption of single-dose vaccine schedules, raising awareness, and compiling a registry of previously affected results. WHO applauds Bangladesh's Ministry of Health and Family Welfare for its efforts to develop the National Strategy for cervical cancer prevention and control, which will guide and strengthen the country's activities to prevent and treat cervical cancer. Conclusion: The endeavor to eradicate this global disease burden should not be limited to Bangladesh; all nations should participate collectively to prevent the malignancy from returning and threatening human civilization.

Genetic association of Interleukin-17A polymorphism in Bangladeshi patients with breast and cervical cancer: a case-control study with functional analysis.

BACKGROUND: Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer. METHODS: This case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases. RESULTS: From the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015). CONCLUSION: Our study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment.

Natural compounds hold promise in the search for cancer therapies due to their unique chemical structures and combinations that may effectively combat cancer while minimizing toxicity and side effects compared to conventional treatments. Silibinin, a natural lignan, has been found to possess strong anti-cancer activity against several types of human cancers based on emerging research. This study aims to provide an overview of the therapeutic potential of silibinin in the treatment and prevention of cancers. A comprehensive search was conducted using various internet databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant research papers. Silibinin has been shown to exhibit anticancer activity against several types of cancers, including liver, lungs, breast, prostate, colorectal, skin, and bladder cancers. Its multifaceted mechanisms of action contribute to its therapeutic effects. Silibinin exerts antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic activities, making it a promising candidate for cancer therapy. One of the key mechanisms underlying the anticancer effects of silibinin is its ability to modulate multiple signaling pathways involved in cancer development and progression. It can inhibit the activation of various oncogenic pathways, including PI3K/Akt, NF-κB, Wnt/ß-catenin, and MAPK pathways, thereby suppressing cancer cell proliferation, inducing cell cycle arrest, and promoting apoptosis. Silibinin possesses great potential as an effective treatment agent for cancer. The multifaceted mechanisms of action, favorable safety profile, and potential synergistic effects of silibinin with conventional therapies make it an attractive candidate for further investigation and development as a cancer treatment. However, more extensive clinical studies are necessary to fully establish the efficacy, optimal dosage, and long-term effects of silibinin in cancer treatment.

The linkage between IL-6 rs1800797 variant and breast cancer susceptibility in Bangladeshi women: A case-control study.

Background and Aims: Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL-6 single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL-6 in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL-6 and the susceptibility to breast carcinoma among women in Bangladesh. Methods: The IL-6 rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra-primer ARMS-PCR method. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL-6 mRNA analysis, and genotype-based gene expression was retrieved from GTEx Portal. Results: This study found a significant link between IL-6 rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AG vs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AG vs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AA vs. GG: OR = 2.91, p > 0.05) and the recessive model (AA vs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25. Conclusions: A significant relationship was found between the IL-6 rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.

Association of MMP1 gene polymorphisms with breast cancer risk: A narrative review.

Background and Aims: Breast cancer is a multifactorial malignancy with different clinicopathological and molecular characteristics. It is the most frequent cancer in women in terms of both incidence and mortality. Matrix metallopeptidase 1 or MMP1 is a zinc-dependent endopeptidase associated with several physiological processes through the modification of the extracellular matrix and tumor microenvironment. However, previous results did not suggest any concluding remarks on the correlation between MMP1 gene polymorphisms and the risk of breast cancer. Methods: A comprehensive literature search was performed in PubMed database to retrieve relevant articles and extract data from suitable ones. The literature written only in English was selected for this review. Results: A total of 26 articles were included in the present narrative review. From the available studies, it is observed that MMP1 is upregulated in breast cancer tissues and found to be correlated with metastasis and invasion. The expression of MMP1 gene is mediated by numerous factors, including polymorphisms which act as a potential risk factor for the progression of breast cancer. To establish the correlation between genetic polymorphisms in MMP1 and the risk of breast cancer, several case-control studies, as well as genetic analyses, have been carried out in different ethnicities. The association of genetic polymorphisms in MMP1 with the risk and survival of breast cancer in different populations has been reviewed in this study. Moreover, the structural domain of MMP1 and the role of MMP1 in breast cancer metastasis and invasion are also discussed which will help to understand the potential impact of MMP1 as a genetic biomarker. Conclusions: This review provides an overview of the MMP1 gene polymorphisms in breast cancer. However, we recommend future studies concentrating on combined analysis of multiple SNPs, gene-gene interactions, and analysis of epigenetics, proteomics, and posttranscriptional modifications that will provide the best outcome.

MMP-3 -1171 5A/6A promoter polymorphism and cancer susceptibility: an updated meta-analysis and trial sequential analysis.

Purpose: Previous studies of MMP-3 -1171 5A/6A in cancers have produced inconclusive outcomes. This updated meta-analysis was performed to clarify the link between this variant and cancer. Methods: Databases including PubMed, Google Scholar, EMBASE and Cochrane were searched for data collection. The associations were calculated by odds ratios with 95% CIs. Results: 63 eligible studies with 14,252 cases and 15,176 controls were included. The codominant 2, codominant 3, dominant, recessive and allele models were found to be significantly associated with 1.28-, 1.13-, 1.13-, 1.19- and 1.13-fold enhanced overall risk of cancer, respectively. Stratification analysis revealed a 1.28-times enhanced risk of esophageal cancer (codominant 1), 1.29- and 1.26-fold (codominant 3) and 1.18- and 1.28-fold (recessive model) enhanced risk in colorectal and gastrointestinal cancers, respectively, 1.30-, 1.35- and 1.22-times in codominant model 1, dominant and allele models for breast cancer, 1.56-fold (codominant 2) for gynecological cancer and 2.40-times in codominant model 2 for hepatocellular cancer. Conclusion: This meta-analysis suggests a significant association between the MMP-3 -1171 5A/6A variant and cancer. This meta-analysis was registered at INPLASY (registration number: INPLASY202280049).

Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis.

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.

A review of pharmacogenetic studies in the Bangladeshi population.

Pharmacogenetics (PGx)-guided prescribing is an evidence-based precision medicine strategy. Although the past two decades have reported significant advancements in both the quality and quantity of PGx research studies, they are seldom done in developing countries like Bangladesh. This review identified and summarized PGx studies conducted in the Bangladeshi population by searching PubMed and Google Scholar. Additionally, a quality evaluation of the identified studies was also carried out. Eleven PGx studies were identified that looked at the effects of genetic variants on blood thinners (CYP2C9, VKORC1, and ITGB3), cancer drugs (TPMT, MTHFR, DPYD, ERCC1, GSTP1, XPC, XRCC1, TP53, XPD, and ABCC4), statins (COQ2, CYP2D6, and CYP3A5), and prednisolone (ABCB1, CYP3A5, and NR3C1) in the Bangladeshi population. Most studies were of low to moderate quality. Although the identified studies demonstrated the potential for PGx testing, the limited PGx literature in the Bangladeshi population poses a significant challenge in the widespread implementation of PGx testing in Bangladesh.

Analysis of serum calcium, sodium, potassium, zinc, and iron in patients with pre-eclampsia in Bangladesh: A case-control study.

Background and Aims: Pre-eclampsia is a particular type of pregnancy condition. Although the primary etiology of pre-eclampsia is unclear, it hypothesizes that the alteration of trace elements and macro-minerals may play a crucial function in the pathogenesis of Pre-eclampsia. Therefore, our research sought to ascertain the serum level of trace elements (zinc, iron) and macro-minerals (sodium, calcium, potassium) and their possible association with pre-eclampsia. Methods: The present study was conducted with 74 pre-eclampsia pregnant women (case) and 118 pregnant women having normal blood pressure (controls). Atomic Absorption Spectroscopy determined the serum level of trace components and electrolytes. Results: The researchers discovered notable differences in maternal age, gestational period, body mass index, systolic and diastolic blood pressure, hemoglobin, and creatinine level. Results of serum analysis revealed that calcium (52.06 ± 3.71 mg/L vs. 65.93 ± 2.57 mg/L, p < 0.05) and potassium (63.44 ± 5.33 mg/L vs. 102.54 ± 4.25 mg/L, p < 0.001) concentrations were substantially lower in the patient group than in control. Serum zinc (0.34 ± 0.02 mg/L vs. 0.52 ± 0.02 mg/L, p < 0.001) and iron (0.38 ± 0.03 mg/L vs. 0.46 ± 0.02 mg/L, p < 0.05) concentration were also considerably decreased in pre-eclampsia participants compared with a pregnant normotensive group. Pearson's correlation research results in the patient group revealed a connection between trace elements or macro minerals. In addition, the systolic blood pressure was positively correlated with sodium (r = 0.392, p < 0.01) and negatively correlated with potassium (r = -0.257, p < 0.05) in the control group. Conclusions: This study concludes that calcium, potassium, iron, and zinc levels were lower, whereas sodium levels were higher in Bangladeshi pre-eclampsia patients compared to controls. These findings with Pearson's correlation and the inter-element relationship between the patient and a control subject results can act as critical indication factors for patients with pre-eclampsia in Bangladesh and, as a result, may require a higher intake of calcium, potassium, iron, and zinc for effective therapeutic intervention and reduce the intake of sodium.

MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta-analysis.

BACKGROUND: Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the potential impact of MAP3K1 rs889312 SNP on the prognosis of various cancers, this meta-analysis was performed to obtain solid and credible evidence. METHODS AND MATERIALS: This study was performed according to the PRISMA 2020 statement. A comprehensive article search was conducted to find and select articles from multiple databases, including PubMed, Google Scholar, Web of Science, EMBASE and the Cochrane Library, published up to 15th September 2022. The data analysis was performed with Review Manager v5.2. Pooled HR with its 95% CI and p-value was calculated where HR >1 suggests worse/poor survival and HR <1 suggests better survival of cancer patients. RESULTS: A total of five articles comprising 24 439 patients were included for both qualitative and quantitative data synthesis. It was found that only the dominant genetic model (AC + CC vs. AA) showed a statistically significant poor overall survival for MAP3K1 rs889312 polymorphism (HR = 1.25, 95% CI = 1.06-1.47, p = .01). In addition, publication bias analysis by the Egger's test and the Begg-Mazumdar test reported no significant bias in the analysis of overall survival (p > .05). CONCLUSIONS: The present study concludes that MAP3K1 gene rs889312 polymorphism plays a prognostic role in the survival of cancer patients. However, future research is recommended that will analyze more MAP3K SNPs along with rs889312, which may reveal more credible outcomes in terms of cancer prognosis.

TGFß1 rs1800469 and SMAD4 rs10502913 polymorphisms and genetic susceptibility to colorectal cancer in Bangladeshi population.

BACKGROUND: Among Bangladeshi males and females, colorectal cancer is the fourth and fifth most prevalent cancer, respectively. Several studies have shown that the transforming growth factor beta 1 (TGFß1) gene and SMAD4 gene have a great impact on colorectal cancer. OBJECTIVE: The present study aimed to investigate whether TGFß1 rs1800469 and SMAD4 rs10502913 genetic polymorphisms are associated with susceptibility to colorectal cancer in the Bangladeshi population. METHODS AND MATERIALS: This case-control study was performed on 167 colorectal cancer patients and 162 healthy volunteers, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed for genotyping. RESULTS: In case of SMAD4 rs10502913 G > A polymorphism, the A allele reduced the colorectal cancer risk significantly (adjusted OR 0.35, 95% CI 0.23-0.52, p < 0.001) when compared to the G allele. It was also found that G/A and A/A genotypes of SMAD4 rs10502913 G > A polymorphism reduced the risk of colorectal cancer in comparison to the G/G genotype (G/A vs. G/G: adjusted OR 0.24, 95% CI 0.12-0.45, p < 0.001 and A/A vs. G/G: adjusted OR 0.06, 95% CI 0.02-0.21, p < 0.001). TGFß1 rs1800469 C > T polymorphism showed an elevated risk of developing colorectal cancer, although the results were not statistically significant. CONCLUSION: This study confirms the association of SMAD4 rs10502913 gene polymorphism with colorectal cancer susceptibility among the Bangladeshi population.

Polymorphisms in IL-17A Gene and Susceptibility of Colorectal Cancer in Bangladeshi Population: A Case-Control Analysis.

OBJECTIVE: Interleukin-17A (IL-17A) genetic polymorphisms are associated with multiple cancer types, including colorectal cancer (CRC). However, no previous study was performed in the Bangladeshi population to evaluate the association. Our study aimed to find the association between two IL-17A variants (rs10484879 C/A and rs3748067 G/A) and susceptibility of CRC. METHODS AND MATERIALS: This retrospective case-control study comprised 292 CRC patients and 288 age, sex, and BMI matched healthy volunteers. Genotyping of both variants was done by the tetra-primer ARMS-PCR method, and the results were analyzed by the SPSS software package (version-25.0). RESULTS: Logistic regression analysis indicated that in case of IL-17A rs10484879 polymorphism, AC and AA genotype carriers showed 2.44- and 3.27-times significantly increased risk for CRC development (OR = 2.44, P = .0008 and OR = 3.27, P = .0133, individually). A significant association was also observed for AC + AA genotype (OR = 2.58, P = .0001). Again, over-dominant and allelic model revealed statistically significant link to CRC risk (OR = 2.13, P = .0035 and OR = 2.22, P = .001). For rs3748067 polymorphism, AG and AA genotype carriers showed 2.30- and 2.45-times enhanced risk for CRC (OR = 2.30, P = .005 and OR = 2.45, P = .031). A statistically significant association was also observed for AG + AA genotype (OR = 2.35, P = .001), over-dominant model (OR = 2.05, P = .014), and allelic model (OR = 2.11, P = .0004). CONCLUSION: This study highlights that IL-17A rs10484879 and rs3748067 polymorphisms may be associated with CRC development. However, further functional research with larger samples may reveal more statistically significant outcomes.

Susceptibility of TNFAIP8, TNFAIP8L1, and TNFAIP2 Gene Polymorphisms on Cancer Risk: A Comprehensive Review and Meta-Analysis of Case-Control Studies.

Objectives: The TNFAIP8 gene family and TNFAIP2 gene are inextricably linked to an elevated risk of cancer development. This systemic review and meta-analysis seeks to establish the relationship between TNFAIP8 (rs11064, rs1045241, rs1045242, and rs3813308), TNFAIP8L1 (rs1060555), and TNFAIP2 (rs710100 and rs8126) polymorphisms with the risk of cancer. Methods and Materials: A systematic search of multiple databases from January 2022 to April 2022 was used to identify relevant studies. Odds ratios (ORs) with corresponding 95% CI and p-value were calculated to assess the association. Bonferroni correction was performed to correct p-values. Trial sequential analysis (TSA) and in-silico messenger RNA expression were also performed. Review Manager 5.4 software was used for performing this meta-analysis. Results: This study comprised 6909 cancer patients and 7087 healthy participants from 14 studies. Four genetic models of rs11064 (codominant 2 [COD2]: OR = 2.30, p = 7.83 × 10-5; codominant 3 [COD3]: OR = 2.10, p = .0006; recessive model [RM]: OR = 2.24, p = .0001; AC: OR = 1.47, p = .037), two genetic models of rs1045241 (codominant 1 [COD1]: OR = 1.27, p = .009; overdominant model [ODM]: OR = 1.24, p = .018), four genetic models of rs1045242 (COD1: OR = 1.52, p = .005; dominant model (DM): OR = 1.56, p = .002; OD: OR = 1.48, p = .008; AC: OR = 1.48, p = .002), and three genetic models of rs8126 (COD2: OR = 1.41, p = .0005; COD3: OR = 1.44, p = .0002; RM: OR = 1.43, p = .0001) were statistically linked to cancer risk. Only one genetic model of rs1060555 polymorphism showed a significant protective association with cancer (COD2: OR = 0.80, p = .048). The outcomes of TSA also validated the findings of the meta-analysis. Conclusion: This study summarizes that rs11064, rs1045241, and rs1045242 polymorphisms of TNFAIP8 gene and rs8126 polymorphism of TNFAIP2 gene are significantly linked with the risk of cancer development. This meta-analysis was registered at INPLASY (registration number: INPLASY202270073).

Association between TP73 G4C14-A4T14 polymorphism and different cancer types: an updated meta-analysis of 55 case-control studies.

OBJECTIVE: The TP73 G4C14-A4T14 variant has been associated with elevated cancer risk, but the evidence is inconclusive. We performed a meta-analysis to clarify the role of this variant in cancer development. METHODS: Eligible literature was selected by searching PubMed, Google Scholar, Cochrane Library, and Embase. The meta-analysis was performed using Review Manager 5.4. RESULTS: A meta-analysis of 55 case-control studies showed that the G4C14-A4T14 variant was significantly associated with overall cancer development in five genetic models, including the allele model (AM), codominant model 1 (COD1), COD2, dominant model (DM), and over-dominant model (OD). Sub-group analysis based on ethnicity showed significantly higher risks in Africans in COD2 and RM and in Whites in AM, COD2, DM, and recessive model (RM). Cancer-specific subgroup analysis identified significant risks of gynecological (ovarian, cervical, and endometrial cancer), colorectal, oral, head and neck, and other cancers. Moreover, hospital-based controls revealed significant cancer risks in the AM, COD1, COD2, DM, and RM genetic models. Our findings were confirmed by trial sequential analysis. CONCLUSION: This meta-analysis confirmed that TP73 G4C14-A4T14 significantly elevates the overall cancer risk, especially in White, African, and hospital-based populations, and specifically predisposes individuals to gynecological, colorectal, oral, and head and neck cancers.This meta-analysis was registered at INPLASY (registration number: INPLASY202210070).

Catalase C262T genetic variation and cancer susceptibility: A comprehensive meta-analysis with meta-regression and trial sequential analysis.

Several genetic association studies have analyzed the link between the catalase (CAT) C262T variant and different cancers, but the findings remain controversial. Our research centered on establishing a comprehensive correlation between the C262T variant and different cancers. This study was conducted using RevMan 5.4 software following the PRISMA 2020 guidelines. For this meta-analysis, 53 case-control studies (18,258 cases and 47,476 controls) were chosen. The analysis revealed that three genetic models were statistically linked (P < 0.05) to overall cancer susceptibility in codominant model 2 (COD2): odds ratio (OR) = 1.16, COD3: OR = 1.21, recessive model (RM): OR = 1.20). After stratification by ethnicity, a significant link (P < 0.05) was found in Caucasians (COD2: OR = 1.18, COD3: OR = 1.17, over-dominant model (ODM): OR = 1.19) and Asians (COD3: OR = 1.49). Subgroup analyses revealed a significant correlation (P < 0.05) with blood-and-bone-marrow-related cancer, skin cancer, gastrointestinal-tract-related cancer, prostate cancer, and gynecologic cancer. Three genetic models in population-based controls (COD2: OR = 1.19, COD3: OR = 1.17, RM: OR = 1.19) and two genetic models in hospital-based controls (COD3: OR = 1.40, RM: OR = 1.24) were found to be significantly correlated (P < 0.05) with cancer. Also, three genetic models for polymerase chain reaction-restriction fragment length polymorphism (COD3: OR = 1.46; RM: OR = 1.34, ODM: OR = 0.80) and three models for MALDI-TOF + MassARRAY (COD2: OR = 1.32, RM: OR = 1.26, allele model: OR = 1.14) genotyping methods showed significant association (P < 0.05) with cancer. The meta-regression showed that the quality scores might be a source of significant heterogeneity under the COD2 model (coefficient = 0.176, P = 0.029). Trial sequential analysis also validated the adequacy of the sample size on overall findings. Our results indicate that CAT C262T variant is associated with overall cancer susceptibility, especially in Caucasians and Asians. This variant may also be associated with blood-and-bone-marrow-related, GIT-related, prostate, skin, and gynecological cancers.

Effect of miR-196a2 rs11614913 Polymorphism on Cancer Susceptibility: Evidence From an Updated Meta-Analysis.

Background:MiR-196a2 rs11614913 polymorphism has been studied in a wide range of cancers throughout the years. Despite a large number of epidemiological studies performed in almost all ethnic populations, the contribution of this polymorphism to cancer risk is still inconclusive. Therefore, this updated meta-analysis was performed to estimate a meticulous correlation between miR-196a2 rs11614913 variant and cancer susceptibility. Methods: A systematic study search was carried out using PubMed, ScienceDirect, CNKI, EMBASE, Scopus, and Google Scholar databases following PRISMA guidelines to find necessary literature up to December 15, 2021. Pooled odds ratios with corresponding 95% confidence intervals were estimated using RevMan 5.4 based on ethnicities, cancer types, control sources, and genotyping methods. Results: A total of 152 studies, including 120 135 subjects (53 818 patients and 66 317 controls; 140 studies, after removing studies that deviated from HWE: 51 459 cases and 62 588 controls), were included in this meta-analysis. Quantitative synthesis suggests that the miR-196a2 rs11614913 genetic variant is significantly correlated with the reduced risk of overall cancer in CDM2, CDM3, RM, and AM (odds ratio < 1 and P < .05). It is also observed from ethnicity-based subgroup analysis that rs11614913 polymorphism is significantly (P < .05) linked with cancer in the Asian (in CDM2, CDM3, RM, AM) and the African population (in CDM1, CDM3, ODM). Stratified analysis based on the cancer types demonstrated a significantly decreased correlation for breast, hepatocellular, lung, and gynecological cancer and an increased association for oral and renal cell cancer. Again, the control population-based subgroup analysis reported a strongly reduced correlation for HB population in CDM2, RM, and AM. A substantially decreased risk was also observed for other genotyping methods in multiple genetic models. Conclusions:MiR-196a2 rs11614913 variant is significantly correlated with overall cancer susceptibility. Besides, rs11614913 is correlated with cancer in Asians and Africans. It is also correlated with breast, gynecological, hepatocellular, lung, oral, and renal cell cancer.

Propagation of age-related diseases due to the changes of lipid peroxide and antioxidant levels in elderly people: A narrative review.

Background and Aims: Lipid peroxidation end products are the major culprit for inducing chronic diseases in elderly people. Along with the elevated level of lipid peroxide biomarkers, there is a significant disruption of antioxidants balance, which combinedly propagate the diseases of elderly people. The aim of the present review is to bridge the connection of changes in lipid peroxides biomarkers and antioxidants level with age-associated diseases in elderly people. Methods: This narrative review was performed following a comprehensive search for suitable articles in multiple online databases, including PubMed, Google Scholar, EMBASE, Web of Science, Cochrane Library, and ScienceDirect using selected search terms. The most appropriate literature was included based on the selection criteria. Results: From the review, it is found that many age-related diseases propagated with an increased level of the end products of lipid peroxide and reduced levels of antioxidants in elderly people. When the end products of lipid peroxidation increase in the body, it creates oxidative stress, which ultimately leads to many complicated diseases, including cancers, cardiovascular and neurogenic diseases, and many other chronic inflammatory diseases. The oxidative stress induced by peroxidation can be assessed by different lipid peroxide end products such as malondialdehyde, oxidized low-density lipoprotein, isoprostanes, neuroprostanes, lipoperoxides, oxysterols (7-ketocholesterol, 7ß-hydroxycholesterol), and many more. Conclusions: This study definitively answers the correlation between the changes in lipid peroxides and antioxidants level and age-related diseases. Our narrative article recommends future investigations for elucidating the mechanisms rigorously to establish a compact correlation.

Exploring the role of senescence inducers and senotherapeutics as targets for anticancer natural products.

During the last few decades, cancer has remained one of the deadliest diseases that endanger human health, emphasizing urgent drug discovery. Cellular senescence has gained a great deal of attention in recent years because of its link to the development of cancer therapy. Senescent cells are incapable of proliferating due to irreversibly inhibition of the initiation of the cell cycle pathways. However, senescent cells aggregate in tissues and produce a pro-inflammatory secretome called senescence-associated secretory phenotype (SASP) that can cause serious harmful effects if not managed properly. There is mounting evidence that senescent cells lead to various phases of tumorigenesis in various anatomical sites, owing mostly to the paracrine activities of the SASP. Therefore, a new treatment field called senotherapeutics has been established. Senotherapeutics are newly developed anticancer agents that have been demonstrated to inhibit cancer efficiently. In light of recent findings, several promising natural products have been identified as senescence inducers and senotherapeutics, including, miliusanes, epigallocatechin gallate, phloretin, silybin, resveratrol, genistein, sulforaphane, quercetin, allicin, fisetin, piperlongumine, berberine, triptolide, tocotrienols and curcumin analogs. Some of them have already been validated through preclinical trials and exert an enormous potential for clinical trials. This review article focuses on and summarizes the latest advances made on cellular senescence and its potential as a target for cancer treatment and highlights the well-known natural products as senescence inducers and senotherapeutics for cancer treatment.