A possible influence of reproductive and menstrual factors on familial risk of BC has been suggested previously and was also evident in the present study. Three-way interactions between age, family history and parity or age at first childbirth might exist and they merit further investigation.
In a previous study in France, we reported that the relative risk of breast cancer associated with a family history of breast cancer was higher in those subjects with a history of abortions. The present study was undertaken to check the existence of this interaction in other studies and to investigate whether the interaction is modified by the time at which abortions occur. Data were obtained from six case-control studies in France, Australia and Russia, with information on family history of breast cancer and abortion for 2693 breast cancer cases and 3493 controls. The interaction effect was estimated in each study separately, then combined using a multivariate weighted average. The relative risk conferred by a family history of breast cancer increased with the number of abortions (1.8 for no abortion, 1.9 for one abortion, 2.8 for two or more). There was a significant interaction between total number of abortions and family history (P = 0.04), but this was no longer significant when adjusted for other risk factors. The familial risk was highest for those who had had an abortion before first childbirth (1.9 for abortion after first childbirth, 2.7 for abortion before first childbirth). The adjusted risk associated with family history was significantly higher in those with an abortion before first childbirth (P = 0.04). Our findings suggest a synergism between familial factors and abortion. The interaction was not substantially modified by the type of abortion (spontaneous or induced) but was modified by the time at which it occurred in relation to first childbirth. This suggests an effect of abortion itself rather than predisposition to abortion. Further studies of breast cancer cases, particularly among BRCA1 gene carriers and their families, could improve our understanding of this effect.
At present, the new technologies of DNA sequencing are rapidly developing allowing quick and efficient characterisation of organisms at the level of the genome structure. In this study, the whole genome sequencing of a human (Russian man) was performed using two technologies currently present on the market - Sequencing by Oligonucleotide Ligation and Detection (SOLiD™) (Applied Biosystems) and sequencing technologies of molecular clusters using fluorescently labeled precursors (Illumina). The total number of generated data resulted in 108.3 billion base pairs (60.2 billion from Illumina technology and 48.1 billion from SOLiD technology). Statistics performed on reads generated by GAII and SOLiD showed that they covered 75% and 96% of the genome respectively. Short polymorphic regions were detected with comparable accuracy however, the absolute amount of them revealed by SOLiD was several times less than by GAII. Optimal algorithm for using the latest methods of sequencing was established for the analysis of individual human genomes. The study is the first Russian effort towards whole human genome sequencing.
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