Survival of primary lung cancer patients in Brunei Darussalam, 1987-2012.

BACKGROUND: In 2009 to 2011, the commonest cause of death was by cancer in Brunei Darussalam, and 16.5% and 19.5% of cancer deaths were due to lung cancer in 2004 and 2011 respectively. This study was to investigate the survival of lung cancer patients in Brunei Darussalam. METHODS: This retrospective cohort study was conducted in 2013 & 2014 for those who were diagnosed as primary lung cancer in the period of 1987 to 2012. Data were retrieved from patients' medical records and death certificates using pretested data collection form. Survival analyses namely Kaplan-Meier method, and log-rank test to compare survival between groups. RESULTS: We retrieved 630 primary lung cancer records. Majority was diagnosed at the late stages, 42.5% at Stage IV & 33.4% at Stage III. The overall median survival time was 6.1 months whereas 2.6 and 79.1 months for Stage IV and Stage I respectively. The overall 6-month, 1-, 3- and 5-year survival rates were 50.2%, 32.1%, 14.5% and 8.8% respectively. Survival duration had significantly improved from 1987-1999 to 2000-2012 (P=0.001) although significant higher proportion of Stage IV was diagnosed in the second period (P=0.008). CONCLUSIONS: Overall survival rates and duration of primary lung cancer in Brunei Darussalam were comparable with some developed countries. However, through effective public intervention such as increase awareness, early case detection, and effective anti-smoking strategies, survival of lung cancer patients can certainly be improved and the burden of disease can be reduced.

Selective sweep on human amylase genes postdates the split with Neanderthals.

Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content.

Genomic insights into the peopling of the Southwest Pacific.

The appearance of people associated with the Lapita culture in the South Pacific around 3,000 years ago marked the beginning of the last major human dispersal to unpopulated lands. However, the relationship of these pioneers to the long-established Papuan people of the New Guinea region is unclear. Here we present genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100-2,700 years before present) and one from Tonga (about 2,700-2,300 years before present), and analyse them with data from 778 present-day East Asians and Oceanians. Today, indigenous people of the South Pacific harbour a mixture of ancestry from Papuans and a population of East Asian origin that no longer exists in unmixed form, but is a match to the ancient individuals. Most analyses have interpreted the minimum of twenty-five per cent Papuan ancestry in the region today as evidence that the first humans to reach Remote Oceania, including Polynesia, were derived from population mixtures near New Guinea, before their further expansion into Remote Oceania. However, our finding that the ancient individuals had little to no Papuan ancestry implies that later human population movements spread Papuan ancestry through the South Pacific after the first peopling of the islands.

Multi-layered population structure in Island Southeast Asians.

The history of human settlement in Southeast Asia has been complex and involved several distinct dispersal events. Here, we report the analyses of 1825 individuals from Southeast Asia including new genome-wide genotype data for 146 individuals from three Mainland Southeast Asian (Burmese, Malay and Vietnamese) and four Island Southeast Asian (Dusun, Filipino, Kankanaey and Murut) populations. While confirming the presence of previously recognised major ancestry components in the Southeast Asian population structure, we highlight the Kankanaey Igorots from the highlands of the Philippine Mountain Province as likely the closest living representatives of the source population that may have given rise to the Austronesian expansion. This conclusion rests on independent evidence from various analyses of autosomal data and uniparental markers. Given the extensive presence of trade goods, cultural and linguistic evidence of Indian influence in Southeast Asia starting from 2.5 kya, we also detect traces of a South Asian signature in different populations in the region dating to the last couple of thousand years.

Germline hemizygous deletion of CDKN2A-CDKN2B locus in a patient presenting with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome usually associated with TP53 germline alterations. Its genetic basis in TP53 wild-type pedigrees is less understood. Using whole-genome sequencing, we identified a germline hemizygous deletion ablating CDKN2A-CDKN2B in a TP53 wild-type patient presenting with high-grade sarcoma, laryngeal squamous cell carcinoma and a family history suggestive of LFS. Patient-derived cells demonstrated reduced basal gene and protein expression of the CDKN2A-encoded tumour suppressors p14ARF and p16INK4A with concomitant decrease in p21 and faster cell proliferation, implying potential deregulation of p53-mediated cell cycle control. Review of 13 additional patients with pathogenic CDKN2A variants suggested associations of germline CDKN2A mutations with an expanded spectrum of non-melanoma familial cancers. To our knowledge, this is the first report of a germline gross deletion of the CDKN2A-CDKN2B locus in an LFS family. These findings highlight the potential contribution of germline CDKN2A deletions to cancer predisposition and the importance of interrogating the full extent of CDKN2A locus in clinical testing gene panels.