Association of common ATMvariants with familial breast cancer in a South American population

González‐Hormazábal, Patricio; Bravo, Teresa; Blanco, Rafael; Valenzuela, Carlos Y; Gómez, Fernando; Waugh, Enrique; Peralta, O; Ortuzar, Waldo Feliu; Reyes, José M.; Jara, Lilian

doi:10.1186/1471-2407-8-117

Cited by 32 publications

(38 citation statements)

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“…The ATM kinase has an essential role maintaining genomic integrity, as a key activator of cellular responses to DNA double-strand breaks [61]. In Chile and Mexico, association studies were performed to evaluate the relationship between common ATM variants and familial BC [62,63]. The same variants were studied in both countries: IVS24-9delT and IVS38-8T>C. Both reports concluded that these variants are associated with increased risk of BC (Table 5).…”

Section: Other Bc Susceptibility Mutations In Central and South Amerimentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

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Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate-and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

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Section: Other Bc Susceptibility Mutations In Central and South Amerimentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

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“…All of these were in heterozygous state, very similar to the results found in this study, indicating that being the carrier of one of these alleles alone or in combination may alter the risk for cancer, probably through increased genetic instability or through altering the normal response for DNA damage repair, as described previously. 10 Additionally, we found that haplotype T/(-T), TT, G/G appear to confer risk to BC (OR 3.41; CI 1.38-8.43); however, as can be seen in table I, in this case such risk should be attributable in fact to allele IVS24-9delT (T/-T).…”

Section: Discussionmentioning

confidence: 62%

“…10 For polymorphism 5557G>A, the authors described a heterozygous frequency of 20.6% in cases and of 13% in controls. Similar frequencies were found for the variant IVS24-9delT.…”

Section: Discussionmentioning

confidence: 99%

“…González-Hormazábal and colleagues found variants in the ATM gene in a study of 137 Chilean patients with familial BC negative for mutations in BRCA1/2, in which they analyzed polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A (the latter more common, with 20.6%), and concluded that these three genotypes alone or in combination plus environmental factors may alter the risk for BC through increasing genetic instability or by altering the DNA damage response. 10 This study was, to our knowledge, the first indication of the importance of this mutation in Latin American population.…”

Section: Studies Of Polymorphism 5557g>amentioning

confidence: 99%

“…Three of these, which are most often studied, are 9delT-IVS24, IVS38-8T>C, and 5557G>A. 10 It has been reported that female carriers of these variants have a higher occurrence of bilateral BC, early disease onset, radio-sensitivity, and long survival rates. 11,12 In contrast, other studies have failed to find this association.…”

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ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

Calderón-Zúñiga¹,

Ocampo-Gomez²,

López-Márquez³

et al. 2014

Salud Publica Mex

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ResumenObjetivo. Evaluar si en la población mexicana las frecuencias de los polimorfismos IVS-9delT, IVS38-8T>C y 5557G>A en casos de cáncer de mama y en controles sanos son diferentes de las encontradas en otros países. Material y métodos. Los polimorfismos IVS24-9delT, IVS38-8T>C y 5557G>A fueron analizados mediante PCR-RFLPs en 94 pacientes con CM de tipo familiar o de inicio temprano y 97 testigos seleccionadas de forma aleatoria. El análisis de la frecuencia alélica se hizo mediante χ 2 y equilibrio de HardyWeinberg. Resultados. Las frecuencias de heterocigotos fueron 5557G>A, 13% de casos, 0% de testigos (p=0.0009); IVS24-9delT, 21% de casos, 8% de testigos (p=0.0122); IVS38-8T>C, sólo un caso. 5557G>A y IVS24-9delT fueron más frecuentes en casos que en testigos. Las frecuencias alélicas encontradas en 5557G>A son similares a las descritas por González-Hormazábal en Chile. Conclusión. La similitud de resultados en este polimorfismo entre la población chilena y mexicana puede ser debida a que ambas son mestizas con un componente amerindio-español. Las diferencias encontradas podrían explicarse porque la población chilena tiene mayor componente europeo que la mexicana. AbstractObjective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8-T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ 2 and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican's.

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Description and validation of high-throughput simultaneous genotyping and mutation scanning by high-resolution melting curve analysis

et al. 2009

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Mutation scanning using high-resolution melting curve analysis (HR-melt) is an effective and sensitive method to detect sequence variations. However, the presence of a common SNP within a mutation scanning amplicon may considerably complicate the interpretation of results and increase the number of samples flagged for sequencing by interfering with the clustering of samples according to melting profiles. A protocol describing simultaneous high-resolution gene scanning and genotyping has been reported. Here, we show that it can improve the sensitivity and the efficiency of large-scale case/control mutation screening. Two exons of ATM, both containing a SNP interfering with standard mutation scanning, were selected for screening of 1356 subjects from an international breast cancer genetics study. Asymmetric PCR was performed in the presence of a SNP-specific unlabeled probe. Stratification of the samples according to their probe-target melting was aided by customized HR-melt software. This approach improved identification of rare known and unknown variants, while dramatically reducing sequencing effort. It even allowed genotyping of tandem SNPs using a single probe. Hence, HR-melt is a rapid, efficient and cost-effective tool that can be used for high-throughput mutation screening for research, as well as for molecular diagnostic and clinical purposes.

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Association of common ATMvariants with familial breast cancer in a South American population

Abstract: Background: The ATM gene has been frequently involved in hereditary breast cancer as a lowpenetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory.

Cited by 32 publications

References 27 publications

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

Description and validation of high-throughput simultaneous genotyping and mutation scanning by high-resolution melting curve analysis

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