MLH1 Ile219Val Polymorphism in Argentinean Families with Suspected Lynch Syndrome

Dominguez‐Valentin, Mev; Wernhoff, Patrik; Cajal, Andrea R.; Kalfayan, Pablo; Piñero, Tamara Alejandra; González, María Laura; Ferro, Alejandra; Sammartino, Inés; Calo, Natalia S. Causada; Vaccaro, Carlos

doi:10.3389/fonc.2016.00189

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…This whole process of network construction and research development on hereditary cancer in Latin America prepares the ground for global Latin American collaborations on increasing the knowledge of MMR variants in different populations and to bring additional awareness of this condition to medical professionals and public health leaders in this region. Since its inception, more than ten international scientific publications have been generated in hereditary CRC by our network . Furthermore, Argentina, Uruguay and Chile have initiated their participation on the PLSD, providing information of a total of 128 prospective path_MMR carriers to enrich the global database of variation.…”

Section: Latin American Hereditary Crc Collaborative Research Networkmentioning

confidence: 99%

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Vaccaro

López-Köstner

Adriana

et al. 2018

Intl Journal of Cancer

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Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

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Section: Latin American Hereditary Crc Collaborative Research Networkmentioning

confidence: 99%

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Vaccaro

López-Köstner

Adriana

et al. 2018

Intl Journal of Cancer

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“…However, since both alleles code for nonpolar pH-neutral amino acids, the substitution is considered conservative and not expected to result in drastic changes in protein properties and function [ 73 ]. Several functional studies support this hypothesis [ 73 , 74 , 105 , 106 , 107 ] but the existence of a more subtle effect should not be excluded [ 73 , 106 , 108 , 109 ] as an association between the G variant allele and reduced MLH1 expression has been demonstrated repeatedly in cancer patients [ 74 , 75 , 76 , 77 ]. Moreover, two recent meta-analyses have associated this variant with increased risk of colorectal cancer [ 110 , 111 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several functional studies support this hypothesis [73,74,[105][106][107] but the existence of a more subtle effect should not be excluded [73,106,108,109] as an association between the G variant allele and reduced MLH1 expression has been demonstrated repeatedly in cancer patients [74][75][76][77]. Moreover, two recent meta-analyses have associated this variant with increased risk of colorectal cancer [110,111].…”

Section: Nbn Rs1805794mentioning

confidence: 99%

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants

Santos

Silva

et al. 2020

Genes

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Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.

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Screening for Hereditary Cancer in Latin America

Álvarez

Domínguez

Carvallo

2018

Genomic Medicine in Emerging Economies

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MLH1 Ile219Val Polymorphism in Argentinean Families with Suspected Lynch Syndrome

Cited by 4 publications

References 38 publications

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants

Screening for Hereditary Cancer in Latin America

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