METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.
RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values
MATERIALS AND METHODS: The EQ- 5D was cross-culturally adapted and translated using an iterative process following standard guidelines. Consenting adult Malay- and Tamil-speaking subjects at a primary care facility in Singapore were interviewed using a questionnaire (including the EQ-5D, a single item assessing global health, the SF-8 and sociodemographic questions) in their respective language versions. Known-groups and convergent construct validity of the EQ-5D was investigated by testing 30 a priori hypotheses per language at attribute and overall levels.
RESULTS: Complete data were obtained for 94 Malay and 78 Indian patients (median age, 54 years and 51 years, respectively). At the attribute level, all 16 hypotheses were fulfilled with several reaching statistical significance (Malay: 4; Tamil: 5). At the overall level, 42 of 44 hypotheses related to the EQ-5D/ EQ-VAS were fulfilled (Malay: 22; Tamil: 20), with 21 reaching statistical significance (Malay: 9; Tamil: 12).
CONCLUSION: In this study among primary care patients, the Singapore Malay and Tamil EQ-5D demonstrated satisfactory known-groups and convergent validity.
CLINICAL FEATURES: A 44-year-old diabetic and alcoholic restaurateur of Chinese-Malay origin, who had been living in Australia for over 20 years, was admitted to hospital with bloody diarrhoea which progressed to fulminant toxaemia and circulatory collapse, and ultimately required laparotomy. Typical pathological features and the isolation of Clostridium perfringens type C from faeces confirmed the diagnosis of enteritis necroticans.
INTERVENTION AND OUTCOME: He was treated initially with ampicillin, gentamicin, metronidazole and chloramphenicol, and later with penicillin and metronidazole, and he required large volumes of intravenously administered fluid and blood for his toxaemic, hypotensive state. Laparotomy was performed as a life-saving procedure. Despite a lengthy convalescence, the patient recovered.
CONCLUSIONS: Enteritis necroticans is a rare disease in developed countries, however it is likely to be underdiagnosed. Clinicians are encouraged to be on the alert for signs of severity that may indicate the need for laparotomy in a predisposed individual with features of this condition.