Ethnic differences in the relationship between body mass index and percentage body fat among Asian children from different backgrounds

Overweight and obesity in Asian children are increasing at an alarming rate; therefore a better understanding of the relationship between BMI and percentage body fat (%BF) in this population is important. A total of 1039 children aged 8-10 years, encompassing a wide BMI range, were recruited from China, Lebanon, Malaysia, The Philippines and Thailand. Body composition was determined using the 2H dilution technique to quantify total body water and subsequently fat mass, fat-free mass and %BF. Ethnic differences in the BMI-%BF relationship were found; for example, %BF in Filipino boys was approximately 2 % lower than in their Thai and Malay counterparts. In contrast, Thai girls had approximately 2.0 % higher %BF values than in their Chinese, Lebanese, Filipino and Malay counterparts at a given BMI. However, the ethnic difference in the BMI-%BF relationship varied by BMI. Compared with Caucasian children of the same age, Asian children had 3-6 units lower BMI at a given %BF. Approximately one-third of the obese Asian children (%BF above 25 % for boys and above 30 % for girls) in the study were not identified using the WHO classification and more than half using the International Obesity Task Force classification. Use of the Chinese classification increased the sensitivity. Results confirmed the necessity to consider ethnic differences in body composition when developing BMI cut-points and other obesity criteria in Asian children.     

Follow-up of women with ASCUS in Chile

Atypical squamous cells of undetermined significance (ASCUS) is a cytological report that creates a dilemma for the cytologist and the clinician because it does not necessarily represent a pathological entity. To clarify this paradox we propose research into the monitoring of cytological and histological results for a period of 3 years from a cohort of women treated in the Primary Care Health Services of Santiago, Chile, who have received a first Pap ASCUS results in 2005. In the cytological reports, the national nomenclature was used, which is equivalent to the Bethesda System 2001. By applying the selection criteria, a cohort of 154 women was formulated, whereby at the end of the monitoring period, we found: 2 women with invasive carcinoma (1.3%), 33 women with high-grade squamous intraepithelial lesions HSIL (21.4%), 32 women with low grade squamous intraepithelial lesions LSIL (20.8%), and 87 women with normal results (56.5%). The statistical analysis, by form of the tree of conditional probabilities, shows that when the 2nd smear is repeated within an accelerated time frame (2.7 months), it does not assist in elucidating this cytological entity, and should be repeated only after 6 months from the first ASCUS smear result. Thus, we found that one out of every two women showed no evidence of abnormal results throughout their cytological and histological monitoring.     

Increased frequency of 20q gain and copy-neutral loss of heterozygosity in mismatch repair proficient familial colorectal carcinomas

Many hereditary nonpolyposis colorectal cancers (CRCs) cannot be explained by Lynch syndrome. Other high penetrance genetic risk factors are likely to play a role in these mismatch repair (MMR)-proficient CRC families. Because genomic profiles of CRC tend to vary with CRC susceptibility syndromes, our aim is to analyze the genomic profile of MMR-proficient familial CRC to obtain insight into the biological basis of MMR-proficient familial CRC. We studied 30 MMR-proficient familial colorectal carcinomas, from 15 families, for genomic aberrations, including gains, physical losses, and copy-neutral loss of heterozygosity LOH (cnLOH) using SNP array comparative genomic hybridization. In addition, we performed somatic mutation analysis for KRAS, BRAF, PIK3CA and GNAS. The frequency of 20q gain (77%) is remarkably increased when compared with sporadic CRC, suggesting that 20q gain is involved in tumor progression of familial CRC. There is also a significant increase in the frequency of cnLOH and, as a consequence, a reduced frequency of physical loss compared with sporadic CRC. The most frequent aberrations observed included gains of 7p, 7q, 8q, 13q, 20p and 20q as well as physical losses of 17p, 18p and 18q. Most of these changes are also observed in sporadic CRC. Mutations in KRAS were identified in 37% of the MMR-proficient CRCs, and mutations in BRAF were identified in 16%. No mutations were identified in PIK3CA or chromosome 20 candidate gene GNAS. We show that the patterns of chromosomal instability of MMR-proficient familial CRC are clearly distinct from those from sporadic CRC. Both the increased gain on chromosome 20 and the increased levels of cnLOH suggest the presence of yet undiscovered germline defects that can, in part, underlie the cancer risk in these families.     

Topoisomerase 2 alpha: a real predictor of anthracycline efficacy?

Anthracyclines are frequently used in the adjuvant setting for breast cancer treatment since it is considered that anthracycline-based chemotherapy treatment benefits breast cancer patients. Nonetheless, these drugs are associated with severe side effects and predictive factors, for sensitivity to anthracyclines, are warranted in clinical practice. Topoisomerase 2 alpha (TOP2A) is considered to be the molecular target of these drugs. The potential predictive value of TOP2A amplification and overexpression has been extensively studied in breast cancer patients treated with anthracyclines. However, results are not conclusive. In this paper, we review some of the published studies addressing the predictive value of TOP2A as well as the cellular functions of this enzyme and its status in breast cancer tissue.     

Characterization of four novel BRCA2 large genomic rearrangements in Spanish breast/ovarian cancer families: review of the literature, and reevaluation of the genetic mechanisms involved in their origin

Large genomic rearrangements (LGRs) at the BRCA2 locus explain a non-negligible proportion of hereditary breast and ovarian cancer (HBOC) syndromes. The multiplex ligation and probe amplification (MLPA) assay has permitted in recent years to identify several families carrying LGRs at this locus, but very few such alterations have been fully characterized at the molecular level. Yet, molecular characterization is essential to identify recurrent alterations, to analyze the genetic mechanisms underlying such alterations, or to investigate potential genotype/phenotype relationships. We have used MLPA to identify BRCA2 LGRs in 7 out of 813 Spanish HBOC families previously tested negative for BRCA1 and BRCA2 small genomic alterations (substitutions and indels) and BRCA1 LGRs. We used a combination of long-range PCR, restriction mapping, and cDNA analysis to characterize the alterations at the molecular level. We found that Del Exon1-Exon2, Del Exon12-Exon16 and Del Exon22-Exon24 explain one family each, while Del Exon2 appears to be a Spanish founder mutation explaining four independent families. Finally, we have combined our data with a comprehensive review of the literature to reevaluate the genetic mechanisms underlying LGRs at the BRCA2 locus. Our study substantially increases the spectrum of BRCA2 LGRs fully characterized at the molecular level. Further on, we provide data to suggest that non-allelic homologous recombination has been overestimated as a mechanism underlying these alterations, while the opposite might be true for microhomology-mediated events.