| 1. |
- Hamdi, Yosr, et al.
(author)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Journal article (peer-reviewed)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 2. |
- Hein, Sascha, et al.
(author)
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Psychological and Sociocultural Adaptation of Children Adopted from Russia and their Associations with Pre-Adoption Risk Factors and Parenting
- 2017
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In: Journal of Child and Family Studies. - : SPRINGER. - 1062-1024 .- 1573-2843. ; 26:10, s. 2669-2680
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Journal article (peer-reviewed)abstract
- We investigated academic and behavioral outcomes of internationally adopted children and the associations between these outcomes and age at adoption, time spent in the adoptive family, and parenting. At two time points (T1 and T2, similar to 15 months apart), we examined early academic skills (school readiness), and parent-reported behavioral adjustment (internalizing and externalizing behavior) and adaptive functioning of a sample of 75 children (45.9% boys, mean age = 5.17 years) adopted from Russia into US families. We also collected parents' self-assessments of their parenting at T1. Children who were adopted at a younger age showed higher levels of early academic skills. Correlations between age at adoption and other outcomes were overall small and mostly non-significant. However, adoptees' academic and behavioral progress differed notably in several respects. Specifically, adoptees improved in early academic skills over time, whereas, as a group, their adaptive functioning and behavioral adjustment remained stable within the normal range. Early academic skills were not related to behavioral adjustment at each time point and over time. The time spent in the adoptive family was positively related to early academic skills at T2. Whereas outcomes showed little to no relation to parenting as reported by mother and father separately, higher discrepancies between mothers' and fathers' reports of positive parenting were related to higher levels of behavioral symptoms and lower levels of adaptive skills at T2. These differential results may be explained in part by drawing upon the notion of dissociated domains of psychological and sociocultural adaptation and acculturation, outlined in the immigration literature. These results also bring to light the possible importance of between-parent consistency in parenting for adoptees' behavioral outcomes.
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| 3. |
- Rakhlin, Natalia, et al.
(author)
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Sources of Heterogeneity in Developmental Outcomes of Children With Past and Current Experiences of Institutionalization in Russia : A Four-Group Comparison
- 2017
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In: American Journal of Orthopsychiatry. - : AMER PSYCHOLOGICAL ASSOC. - 0002-9432 .- 1939-0025. ; 87:3, s. 242-255
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Journal article (peer-reviewed)abstract
- The present study sought to compare 4 groups of age-and gender-matched children-(a) those reared in institutions for children without parental care in Russia; (b) those raised by their biological parents in Russia; (c) those adopted to the United States from Russian institutions; and (d) those born in the United States and raised by their biological parents-on indicators of cognition, language, and early learning. In addition, we aimed to compare the effects of the length of time spent in an institution, the age of initial placement in an institution, the age at adoption, and pre-institutional risk factors (i.e., prenatal substance exposure and prematurity and low birth weight) on the above-mentioned outcomes in the 2 groups of children with institutionalization experiences. Our results confirm previous reports demonstrating negative consequences of institutionalization and substantial ameliorating effects of adoption. They also underscore the complexity of the effects of institutionalization and adoption, showing that they are intertwined with the effects of pre-institutional risk factors.
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