ABSTRACT
Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features; however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing (WES) data to characterize somatic copy number alterations (SCNAs) and mutation profiles in 98 Hong Kong BC (HKBC) patients and compared with those from The Cancer Genome Atlas of European ancestry (TCGA-EA, N = 686), which had similar distributions of age at diagnosis and PAM50 subtypes as in HKBC. We developed a two-sample Poisson model to compare driver gene selection pressure, which reflects the effect sizes of cancer driver genes, while accounting for differences in sample size, sequencing platforms, depths, and mutation calling methods. We found that somatic mutation and SCNA profiles were overall very similar between HKBC and TCGA-EA. The selection pressure for small insertions and deletions (indels) in GATA3 (false discovery rate (FDR) corrected p < 0.01) and single-nucleotide variants (SNVs) in TP53 (nominal p = 0.02, FDR corrected p = 0.28) was lower in HKBC than in TCGA-EA. Among the 13 signatures of single-base substitutions (SBS) that are common in BC, we found a suggestively higher contribution of SBS18 and a lower contribution of SBS1 in HKBC than in TCGA-EA, while the two APOBEC-induced signatures showed similar prevalence. Our results suggest that the genomic landscape of BC was largely very similar between HKBC and TCGA-EA, despite suggestive differences in some driver genes and mutational signatures that warrant future investigations in large and diverse Asian populations.
ABSTRACT
BACKGROUND: Famines have occurred in all areas of the world in every period of history. Many studies have shown that poor growth and development and adverse environmental conditions in childhood are associated with osteoporosis in later life. However, little information is available on the relation between famine and bone health. METHODS: This study examines the hypothesis that past experience of famine has an adverse impact on bone health, using data from Ms Os (Hong Kong), a large cohort study on osteoporosis in Asian women. There were 1,826 Hong Kong women aged 65 years or older recruited from the community. A standardized, structured interview and DXA were performed. Subjects who had experienced famine tended to have lower levels of education, social status and current daily calcium intake. They also have higher rates of cigarette consumption, depression and coronary heart disease. RESULTS: After adjustment for confounders, we found that subjects who had experienced famine have a significantly higher rate of developing osteoporosis than those who had not. CONCLUSIONS: We conclude that past exposure to famine, especially in childhood, is associated with osteoporosis.
