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Title: HRAS1 rare minisatellite alleles and breast cancer in Australian women under age forty years
Authors: Firgaira FA
Seshadri R
McEvoy CR
Dite GS
Giles GG
McCredie MR
Southey MC
Venter DJ
Hopper JL
Keywords: Adult; genetics; Humans; Meta-Analysis; methods; Minisatellite Repeats; Odds Ratio; pathology; Proto-Oncogene Proteins p21(ras); Random Allocation; Research Support,Non-U.S.Gov't; Alleles; Risk; Risk Factors; Women; Australia; breast; Breast Neoplasms; cancer; Case-Control Studies; diagnosis; Female
Pub. Date: 1999
Journal Title: J Natl Cancer Inst
Volume: 91
Issue: 24
Page number start: 2107
Page number end: 2111
Abstract: BACKGROUND: A recent meta-analysis of 23 studies supported the empirically derived hypothesis that women who lack one of the four common minisatellite alleles at the HRAS1 locus are at increased risk of breast cancer. These studies relied on visual sizing of alleles on electrophoretic gels and may have underreported rare alleles. We determined whether this hypothesis applied to early-onset breast cancer by using a new method to size minisatellite alleles. METHODS: We conducted a population-based, case-control-family study of 249 Australian women under 40 years old at diagnosis of a first primary breast cancer and 234 randomly selected women, frequency matched for age. We sized HRAS1 minisatellite alleles with an Applied Biosystems model 373 automated DNA sequencer and GENESCAN(TM) software. All P values are two-sided. RESULTS: We found no association of rare alleles with breast cancer, before or after adjustment for risk factors and irrespective of how their effects were modeled (crude odds ratio = 1.04; 95% confidence interval [CI] = 0.071-1.53; P =.8). The rare allele frequency was 0. 173 (95% CI = 0.149-0.197), three times the pooled estimate of 0.058 (95% CI = 0.050-0.066) from previous studies (P<.001), and was similar for case subjects, 0.177 (95% CI = 0.143-0.221), and control subjects, 0.169 (95% CI = 0.135-0.203) (P =.7). CONCLUSION: There was no support for an association between rare HRAS1 alleles and the risk of early-onset breast cancer, despite 80% power to detect effects of the magnitude of those associations (1.7-fold) previously suggested. IMPLICATIONS: The question of whether cancer risk is associated with rare minisatellite HRAS1 alleles needs to be revisited with the use of new methods that have a greater ability to distinguish rare alleles from similarly sized common alleles
Programme: Breast Cancer McCredie
Division: Cancer Research Division
URI: http://researchpubs.cancercouncil.com.au/cancercounciljspui/handle/1/1361
Appears in Collections:Research Articles

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