METHODS: Germline DNA from 467 breast cancer patients in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated, was sequenced for the entire coding region of BRCA1; BRCA2; PALB2; Exons 6, 7, and 8 of TP53; and Exons 7 and 8 of PTEN. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants, and variants that disrupt splice site.
RESULTS: We found 27 pathogenic variants (11 BRCA1, 10 BRCA2, 4 PALB2, and 2 TP53) in 34 patients, which gave a prevalence of germline mutations of 2.8, 3.23, and 0.86% for BRCA1, BRCA2, and PALB2, respectively. Compared to mutation non-carriers, BRCA1 mutation carriers were more likely to have an earlier age at onset, triple-negative subtype, and lower body mass index, whereas BRCA2 mutation carriers were more likely to have a positive family history. Mutation carrier cases had worse survival compared to non-carriers; however, the association was mostly driven by stage and tumor subtype. We also identified 19 variants of unknown significance, and some of them were predicted to alter splicing or transcription factor binding sites.
CONCLUSION: Our data provide insight into the genetics of breast cancer in this understudied group and suggest the need for modifying genetic testing guidelines for this population with a much younger age at diagnosis and more limited resources compared with Caucasian populations.
OBJECTIVE: This study aimed to investigate the association between human mobility and COVID-19 infections across space and time during the transition period of shifting strategies from restrictions to normal living in Southeast Asia. Our research results have significant implications for evidence-based policymaking at the present of the COVID-19 pandemic and other public health issues.
METHODS: We aggregated weekly average human mobility data derived from the Facebook origin and destination Movement dataset. and weekly average new cases of COVID-19 at the district level from 01-Jun-2021 to 26-Dec-2021 (a total of 30 weeks). We mapped the spatiotemporal dynamics of human mobility and COVID-19 cases across countries in SEA. We further adopted the Geographically and Temporally Weighted Regression model to identify the spatiotemporal variations of the association between human mobility and COVID-19 infections over 30 weeks. Our model also controls for socioeconomic status, vaccination, and stringency of intervention to better identify the impact of human mobility on COVID-19 spread.
RESULTS: The percentage of districts that presented a statistically significant association between human mobility and COVID-19 infections generally decreased from 96.15% in week 1 to 90.38% in week 30, indicating a gradual disconnection between human mobility and COVID-19 spread. Over the study period, the average coefficients in 7 SEA countries increased, decreased, and finally kept stable. The association between human mobility and COVID-19 spread also presents spatial heterogeneity where higher coefficients were mainly concentrated in districts of Indonesia from week 1 to week 10 (ranging from 0.336 to 0.826), while lower coefficients were mainly located in districts of Vietnam (ranging from 0.044 to 0.130). From week 10 to week 25, higher coefficients were mainly observed in Singapore, Malaysia, Brunei, north Indonesia, and several districts of the Philippines. Despite the association showing a general weakening trend over time, significant positive coefficients were observed in Singapore, Malaysia, western Indonesia, and the Philippines, with the relatively highest coefficients observed in the Philippines in week 30 (ranging from 0.101 to 0.139).
CONCLUSIONS: The loosening interventions in response to COVID-19 in SEA countries during the second half of 2021 led to diverse changes in human mobility over time, which may result in the COVID-19 infection dynamics. This study investigated the association between mobility and infections at the regional level during the special transitional period. Our study has important implications for public policy interventions, especially at the later stage of a public health crisis.