Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the ...endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.
Polymorphisms of the KRAS gene have been shown to be associated with cancer. However, their association with breast cancer (BC) has been inconsistent. The purpose of this study was to determine the ...frequency with which the rs61764370, rs9266, and rs140080026 polymorphisms of the KRAS gene are associated with BC in patients of the Mexican population.
The rs61764370 A>C or T>G and rs140080026 A>G polymorphisms were determined by Polymerase Chain Reaction (PCR), and the rs9266 A>G polymorphism was determined by DNA sequencing of healthy Mexican subjects and BC patients.
We observed that 78% of BC patients are overweight and/or obese, 57% have metastatic lymph nodes, 64% have luminal A/B cancer subtypes, and 61% have stage III-IV cancer. The rs61764370 polymorphism was associated with BC susceptibility when the BC patients and the control group were compared for the AC genotype (p = 0.020), AC vs. AA genotypes (heterozygous model: p = 0.016), AC/CC genotype (dominant model: p = 0.002), and the C allele (p = 0.007). The AC/CC genotype (p = 0.018; rs61764370) and AG/GG genotype (p = 0.005; rs9266) were associated with age in BC patients ≥50 years old. The AC/CC (rs61764370) and AG/GG (rs9266) genotypes were classified by molecular subtype, TNM stage, miscarriage, lymph node metastasis, ductal type, and Ki-67. These classifications were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The AAA (OR 0.65, 95% CI 0.43-0.98, p = 0.039) and CAA (OR 3.25, 95% CI 1.13-9.36, p = 0.021) haplotypes were also associated with BC susceptibility. In addition, 94 polymorphisms were identified on the 3'UTR of the KRAS gene GRCh 38/hg3 (25,209,490-25,209,122) in BC (n = 112) and control (n = 113) samples. However, 92 of these polymorphisms have only expressed the major allele (wild-type allele).
The rs61764370 polymorphism in the KRAS gene was associated with BC susceptibility in the Mexican population. The dominant model of the rs61764370 and rs9266 polymorphisms (classified by molecular subtype, miscarriage, TNM stage, lymph node metastasis, and Ki-67) could significantly contribute to BC risk in patients ≥50 years. The CAA haplotype could significantly contribute to BC risk in the Mexican population analyzed.
The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as ...well as to perform in silico assessments of the variants' potential impact.
We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR.
The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs).
The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.
The aim of this investigation was to determine the frequency and association of the variants rs4817415, rs2070424, and rs1041740 of the SOD1 gene in healthy women and breast cancer (BC) patients.
...Genomic DNA samples from 146 healthy women and 130 patients with BC were analyzed.
GG genotype (OR 2.54, 95% CI 1.31-4.91, p = 0.0073) and the G allele (OR 1.37, 95% CI 1.09-1.73, p = 0.007) of the rs2070424 variant and CC genotype (OR 1.67, 95% CI 1.04-0.2.70, p = 0.0444) and allele C (OR 1.58, 95% CI 1.09-2.29, p = 0.0183) of the rs1041740 variant of SOD1 gene were associated as risk factors for BC susceptibility relative to the control group. Study groups comparison of the stratification by menopausal status showed an association of susceptibility to BC risk with carriers of the GG genotype (OR 2.9, 95% CI 1.11-7.81, p = 0.042) of the rs2070424 variant and with the premenopausal status of the study group and the TT (OR 2.89, 95% CI 1.73-4.85, p = 0.001) genotype of the rs1041740 variant. Furthermore, differences were observed in the patients with BC who were carriers of the CC genotype of the rs4817415 variant with elevated Ki-67 (≥ 20%) and who presented lymph node metastasis and stage III-IV BC (p<0.05). Two common haplotypes were identified in the study groups: CAC (protective factor), and CGC (risk factor) (p<0.05).
The rs2070424 and rs1041740 variants of the SOD1 gene and the CGC haplotype were associated as risk susceptibility factors of BC in this sample analyzed.
The rs2234694 and 50 bp insertion/deletion (Ins/Del) polymorphisms of the SOD1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been ...detected. The purpose of this study was to determine the frequency and association of SOD1 gene polymorphisms (rs2234694 and 50 bp Ins/Del) in BC patients in the Mexican population.
The SOD1 polymorphisms were determined by Polymerase Chain Reaction (PCR) in Mexican healthy subjects and BC patients.
The rs2234694 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the AC genotype (p<0.0001), the AC/CC genotype (dominant model: p<0.0001), and the C allele (p<0.0001). The 50 bp Ins/Del polymorphism was associated with BC susceptibility for the Del allele (p=0.048), although the association between the dominant model AC/CC (rs2234694) and BC patients was evident for menopause adjusted odds ratio (OR) 1.65 (95% CI 1.05-2.7); p=0.048, Ki-67 (≥15%) (OR1.9, 95% CI 1.14- 3.16, p=0.016), and the presence of DM2 (OR 2.4, 95% CI 1.35- 4.31, p=0.003). A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for estrogen receptor (ER) and progesterone receptor (PR), carrying the AC genotypes (OR 0.47, 95% CI 0.23-0.94, p= 0.033) and CC (OR 0.11, 95% CI 0.013-1.07, p=0.047). The association between the InsDel/DelDel (dominant model; 50 bp Ins/Del) genotype and BC with metastatic lymph nodes (OR 1.5, 95% CI 1.1-2.25, p=0.019), hematologic toxicity (OR 1.5, 95%CI 1.1-2.23, p=0.015), gastric toxicity (OR 1.5, 95%CI 1.1-2.07, p=0.030), and Ki-67 (≥15%) (OR1.6, 95%CI 1.2-2.26, p=0.002) was evident, indicating that these factors may contribute significantly to BC risk. The C/Ins haplotype was also associated with BC susceptibility (OR3.47, 95% CI 1.62-7.74, p=0.001).
rs2234694 and 50 bp Ins/Del polymorphisms in the SOD1 gene were associated with BC susceptibility in a Mexican population. A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for ER and PR, carrying the AC genotypes. The haplogenotypes AA/InsIns and AC/InsDel could contribute significantly to BC risk in gastric and hematologic toxicities, metastatic lymph nodes, and the presence of DM2 in the Mexican population analyzed.
Background:
Breast cancer is a multifactorial disease whose genetic susceptibility is related to polymorphic variants of cell proliferation and migration pathways. Variants in
AXIN2
and
TCF7L2
in the ...Wnt-β catenin pathway have been associated with different types of cancer; however, little is known about its role in breast cancer. This study tests the hypothesis of links between
AXIN2
rs1133683 and rs2240308, and
TCF7L2
rs7903146 and rs12255372 variants in breast cancer.
Methods:
Peripheral blood samples were obtained from 404 women (202 patients and 202 control females). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology was used to identify the gene variants.
Results:
The
AXIN2
rs2240308 (C > T), and
TCF7L2
rs7903146 (C > T) and rs12255372 (G > T) variants were associated with breast cancer and with age, TNM stage, and histologic-molecular subtype (
p
= 0.001). Likewise, the haplotype T-T in the
TCF7L2
gene (rs7903146-rs12253372) was significantly related with breast cancer (OR = 2.66, 95%, CI = 1.64–4.30,
p
= 0.001).
Conclusion:
Our data show a link between
AXIN2
rs2240308 and
TCF7L2
rs7903146 and rs12255372 variants in breast cancer, and speculate this may be important in pathogenesis.
Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive lysosomal storage disorder caused by a deficiency or absence of α--iduronidase, which is involved in the catabolism of ...glycosaminoglycans (GAGs). This deficiency leads to the accumulation of GAGs in several organs. Given the wide spectrum of the disease, MPS-I has historically been classified into 3 clinical subtypes - severe (Hurler syndrome), intermediate (Hurler-Scheie syndrome), and mild (Scheie syndrome) - none of which is determined by residual enzyme activity. Eleven Mexican patients with MPS-I from northwestern México were evaluated. Diagnoses were confirmed through quantification of GAGs in urine and enzyme assay for α--iduronidase. Regardless of phenotype, all patients had various degrees of infiltrated facies, short stature, dysostosis multiplex, joint contractures, and corneal opacity typical of the disease. A better understanding of the spectrum of this disease can assist in diagnosis, treatment, and improvement in the quality of life for these patients.
The objective of this study was to examine the association between TNF-α serum levels and -308G>A and -238G>A polymorphisms in the corresponding gene by comparing healthy subjects to colorectal ...cancer (CRC) patients from a Mexican population. Serum levels of TNF-α were found to significantly differ between CRC patients and controls (P = 0.001), but no relationship between the -308G>A and -238G>A polymorphisms and increased CRC risk was established (P > 0.05). However, an association between the -308G>A variant and disease became evident when the distribution of AA-GA genotypes was examined in patients with hematologic toxicity (neutropenia) and those without (odds ratio = 3.356, 95% confidence interval = 1.295- 8.698, P = 0.013). The GG haplotype was more common in controls than CRC patients, with a frequency of 0.85 among the former, but this difference was not significant (P > 0.05). In conclusion, TNF-α serum levels and AA-AG genotypes of the TNF-α-308G>A polymorphism may significantly contribute to CRC susceptibility in the population examined in this investigation.
The methylenetetrahydrofolate reductase (MTHFR) gene plays an important role in the steps involved in the processing of amino acids. The analysis of polymorphisms in the MTHFR gene has revealed ...associations with cancer; in particular the C677T polymorphism, which has been suggested to affect folate metabolism, DNA methylation, synthesis, and repair, and to contribute to tumor promotion in the mammary gland. We examined the role of the C677T polymorphism in the MTHFR gene by comparing the C677T genotypes of 339 healthy Mexican women with those of 497 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 10 and 21% for 677TT; 41 and 36% for 677CT; and 49 and 43% for 677CC, respectively. The odds ratio (OR) for the 677TT genotype was 2.5, with a 95% confidence interval (95%CI) of 1.6-3.8; P = 0.0001. The positive association was also evident when the distributions of the 677TT genotype in control and patients affected within the following two categories were compared to alcohol consumption (OR = 0.41; 95%CI = 0.19-0.86; P = 0.018); and high level glutamate-oxaloacetate transaminase (SGOT) (OR = 0.36; 95%CI = 0.15-0.83, P = 0.017). These results suggest that the 677TT genotype of the C677T polymorphism in the MTHFR gene is associated with BC susceptibility in the Mexican population.
The rs1008562, rs2234671 and rs3138060 polymorphisms of the CXCR1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The ...purpose of this study was to determine the frequency and association of the rs1008562, rs2234671 and rs3138060 polymorphisms of CXCR1 gene in BC patients in the Mexican population.
The CXCR1 polymorphisms were determined by Polymerase Chain Reaction (PCR) and real time-PCR in healthy Mexican subjects and BC patients.
The prevalent patron in BC patients was observed, the majority were overweight and obesity (72%) with metastatic lymph nodes (48%), luminal A/B subtypes (63%), and advanced stages (60%). Triple negative breast cancer (TNBC) patients: they were younger (58%) than 43 years old, overweight (33%), obesity (42%), ductal type histological (98%), metastasis to lymph nodes (47%), advanced stages III-IV (61%) and metastasis (33%). The rs2234671 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the CC genotype (p=0.037), CG (heterozygous model: p=0.018), GC/CC (dominant model: p=0.004), and the C allele (p=0.001), as well as the GC/CC genotype with hormone replace therapy (HRT, p=0.016). The rs3138060 polymorphism was associated with BC susceptibility for CG/GG genotype (dominant model: p=0.032) and G allele (p=0.018). Although the association between the dominant model of rs1008562, rs2234671, rs3138060 polymorphisms and BC patients and control was evident for tobacco and alcohol consumption (p<0.05). The rs1008562, rs2234671, and rs3138060 polymorphisms of the CXCR1 gene classified by molecular subtype and stage were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The CCC (OR 1.75, 95% CI 1.03- 2.97, p=0.046), GGG (OR 3.73, 95% CI 1.61- 8.65, p=0.0018) haplotypes were also associated with BC susceptibility.
Rs2234671 and rs3138060 polymorphisms in the CXCR1 gene were associated with BC susceptibility in the Mexican population. The dominant model of the rs1008562, rs2234671 and rs3138060 polymorphisms could significantly contribute to BC risk in tobacco and alcohol consumption, molecular subtype and stage. The rs1008562, rs2234671 and rs3138060 polymorphisms, and the haplotypes CCC and GGG could significantly contribute to BC risk in the Mexican population analyzed.
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