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- Title
Association of common ATM variants with familial breast cancer in a South American population.
- Authors
González-Hormazábal, Patricio; Bravo, Teresa; Blanco, Rafael; Valenzuela, Carlos Y.; Gómez, Fernando; Waugh, Enrique; Peralta, Octavio; Ortuzar, Waldo; Reyes, Jose M.; Jara, Lilian
- Abstract
Background: The ATM gene has been frequently involved in hereditary breast cancer as a low penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. Methods: In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. Results: In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11-8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16-8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. Conclusion: The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response.
- Subjects
CHILE; SOUTH America; CANCER genetics; CANCER susceptibility; BREAST cancer; CANCER risk factors; DNA damage
- Publication
BMC Cancer, 2008, Vol 8, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-8-117