We present, to our knowledge, the first quantitative evidence that music and genes may have coevolved by demonstrating significant correlations between traditional group-level folk songs and mitochondrial DNA variation among nine indigenous populations of Taiwan. These correlations were of comparable magnitude to those between language and genes for the same populations, although music and language were not significantly correlated with one another. An examination of population structure for genetics showed stronger parallels to music than to language. Overall, the results suggest that music might have a sufficient time-depth to retrace ancient population movements and, additionally, that it might be capturing different aspects of population history than language. Music may therefore have the potential to serve as a novel marker of human migrations to complement genes, language and other markers.

DSM-IV criteria for dependence apply to a significant proportion of betel quid users in Asian communities, more so if they use it with tobacco or lime.

Because the mRNA expression of cyclooxygenase-2 (COX-2) is up-regulated by arecoline in human gingival fibroblasts, as shown in our previous study, we further investigated the mRNA expression level of COX-2 and its upstream effectors in three oral epithelial carcinoma cell lines (KB, SAS, and Ca9-22) by using areca nut extract (ANE) and saliva-reacted ANE (sANE). A case-control study of 377 oral squamous cell carcinoma (OSCC) patients and 442 controls was conducted to evaluate the geneenvironment interaction between COX-2 promoter polymorphisms and substance use of alcohol, betel quid, and cigarettes (ABC) in risk of OSCC. The heterogeneous characteristics of the oral site and the COX-2 À1195G>A polymorphism in these cell lines showed diverse inflammatory response (KBJCa9-22>SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-KB activation. In the case-control study, betel chewing [adjusted odds ratios (aOR), 42.2] posed a much higher risk of OSCC than alcohol drinking and cigarette smoking (aORs, 2

This international study gathered data about BQ users across 6 Asian populations, and it demonstrates that DSM-5 symptoms could fulfill a BUD construct. Most current Asian users of BQ already have BUD, which is correlated with risk of OPMD. Among individuals with moderate to severe BUD who used BQ, tolerance and a larger amount or longer history of BQ use are the key symptoms that correlated with enhanced risk of OPMD. These findings play an important role in providing a new indication of an additional psychiatric management plan for users of BQ who have BUD.

A number of genetic variants have been associated with cancer occurrence, however it may be the acquired somatic mutations (SMs) that drive cancer development. This study investigates the potential SMs and related genetic variants associated with the occurrence and development of head and neck squamous cell carcinoma (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution melting analysis and resequencing. Patients who have NOTCH1 SMs show higher 5-year relapse-free recurrence (P = 0.0013) and lower survival proportion (P = 0.0447) when the risk-associated SMs were analysed by Cox proportional hazard models. Interestingly, the NOTCH1 gene rs139994842 that shares linkage with SMs is associated with HNSCC risk (OR = 3.46), increasing when SMs in NOTCH1 are involved (OR = 7.74), and furthermore when there are SMs in conjunction to betel quid chewing (OR = 32.11), which is a related independent environmental risk factor after adjusting for substances use (alcohol, betel quid, cigarettes) and age. The findings indicate that betel quid chewing is highly associated with NOTCH1 SMs (especially with changes in EGF-like domains), and that rs139994842 may potentially serve as an early predictive and prognostic biomarker for the occurrence and development of HNSCC.

Our study found that a newly identified ALPK1 gene can effectively interfere with microRNA target recognition and modulates the mRNA expression; and the varying distribution of the implicated SNPs among cases and controls in the two studied populations suggests a significant role in gout susceptibility.

Gigaxonin, a product of the Giant Axonal Neuropathy (GAN) gene located on chromosome 16, is involved in intermediate filament processing of neural cells and vimentin fibers in fibroblasts. Previous studies have shown an interaction between p16 and gigaxonin in cisplatin mediated ubiquitination of NFkB. Genomic studies have indicated higher frequency (44.25%) of exon 8 single nucleotide polymorphism (SNP) (c.1293 C>T) of gigaxonin in the individuals of Caucasian population compared to normal population (22%). The polymorphism frequency is much lower in individuals of other ethnicities. To determine the relationship to tumors, we analyzed exon 8 polymorphism in HPV positive and negative cervical and head and tumors. Our studies showed a 47.25% polymorphic frequency in these tumors. There was no relationship between the presence of polypmorphism and HPV status. However, there was an inverse relationship between polymorphism and tumor recurrence. Our studies have further shown higher expression of gigaxonin protein in cancer cell lines containing the polymorphic T allele. Growth assays in vitro and in soft agar have shown a direct relationship between the presence of the T allele and slower cell line growth. Our results therefore indicate that in addition to p16 expression, exon 8 SNP could also serve as a diagnostic marker of chemo sensitivity in human tumors. Citation Format: Eri S. Srivatsan, Kimberly J. Hwang, Albert Ko, Jenna R. Chatoff, Saroj K. Basak, Natarajan Venkatesan, Fernando Palma-Diaz, Michael S. Lewis, Pascale Bomont, Marilene B. Wang. Inverse relationship between exon 8 single nucleotide polymorphism (c.1293 C>T) of gigaxonin and human tumor cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4457. doi:10.1158/1538-7445.AM2017-4457

Gigaxonin is the protein product of Giant Axonal Neuropathy (GAN) gene and is involved in the processing of intermediate filaments of neural cells and vimentin fibers in fibroblasts. We have shown earlier that gigaxonin is associated with p16 in NFkB ubiquitination of cisplatin sensitive tumor cells. Our studies have shown that there is a direct relationship between the presence of exon 8 SNP (C>T) and expression of giagxonin in cancer cell lines. We have also seen an inverse relationship between exon 8 SNP and tumor recurrence and metastasis. RNA-seq studies of cancer cell lines and primary tumors have shown a direct relationship in the expression of gigaxonin to the expression of e-cadherin and inverse relationship to the expression of Vimentin and Zeb1. Immunohistochemical (IHC) studies of primary head and neck cancers have confirmed the inverse relationship between e-cadherin and vimentin. We hypothesize therefore that gigaxonin is involved in the ubiquitination of vimentin and cancer stem cell markers such as zeb1 resulting in the chemo sensitization of human tumor cells. Citation Format: Albert Ko, Natarajan Venkatesan, Jenna Chatoff, Marco Morselli, Gregory Fishbein, Pascale Bomont, Matteo Pellegrini, Marilene Wang, Eri Srivatsan. GAN gene exon 8 SNP is related to gigaxonin expression and increased expression of e-cadherin in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5505.