Cigarette smoking is a well-known risk factor of upper digestive diseases. Findings on alcohol's effect on these diseases are inconsistent and with the exception of its association with esophageal cancer, little is known about betel quid chewing. This study investigated the association between use of these three substances and upper digestive diseases. We collected data from 9,275 patients receiving upper endoscopies between April 2008 and December 2013. Polynomial regressions were used to analyze the association between risk factors and diseases of the esophagus, stomach and duodenum. Meta-analysis for use of these substances and esophageal diseases was also performed. Participants who simultaneously consumed cigarettes, alcohol and betel quid had a 17.28-fold risk of esophageal cancer (95% CI = 7.59-39.33), 2.99-fold risk of Barrette's esophagus (95% CI = 2.40-4.39), 1.60-fold risk of grade A-B erosive esophagitis (95% CI = 1.29-2.00), 2.00-fold risk of gastric ulcer (95% CI = 1.52-2.63), 2.12-fold risk of duodenitis (95% CI = 1.55-2.89) and 1.29-fold risk of duodenal ulcer (95% CI = 1.01-1.65). Concurrent consumption of more substances was associated with significantly higher risk of developing these diseases. Meta-analysis also revealed use of the three substances came with a high risk of esophageal diseases. In conclusions, cigarette smoking, alcohol drinking and betel quid chewing were associated with upper digestive tract diseases.

It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a "Negrito" group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome wide data from 26 ancient individuals from northern and southern East Asia spanning 9,500-300 years ago. Genetic differentiation was higher in the past than the present, reflecting a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient samples with Austronesian-related ancestry, supporting a southern China origin for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.

The prevalence of betel quid chewing habit in Taiwan was surveyed in a group of Chinese people from Kaohsiung city and in a second group from the aboriginal inhabitants of South Taiwan. In all 1299 participants constituted Group 1 (85.2% response rate) and 827 Group 2 (70.1% response rate). People were interviewed in their homes in house-to-house survey, according to a structured questionnaire developed and evaluated by the authors. Of the Kaohsiung inhabitants covering all ages and both sexes, 6% was a current betel chewer and 4% was an ex-chewer, whereas 42% of the aborigines aged over 15 yr was a current chewer and 1% an ex-chewer. Lifetime prevalence was 10%. Betel chewing enjoys islandwide popularity among the 20 million inhabitants of Taiwan; the number of current and ex-users was estimated at 2.0 million (95% CI 1.6-2.4 million). The betel quid was prepared in two different ways. In one, used mainly by aborigines, fresh areca nut was simply wrapped with betel leaf and in another, popular mainly among Chinese, a lengthwise piece of betel fruit and lime paste was sandwiched between two halves of an areca nut. A high proportion of chewers was also a smoker and drinker, but tobacco was not found to be chewed together with betel quid. Consumption varied between 14 to 23 portions per day, with individual frequencies ranging widely from 1 to over 200 portions a day. A statistical analysis of sociodemographic factors showed that lesser educated older men, blue collar workers, smokers and drinkers were the likeliest betel chewers.

Blackfoot disease was prevalent in a limited area on the southwest coast of Taiwan, where artesian well water containing arsenic (median = 0.78 ppm arsenic) had been used for many years. Previous studies of arsenic exposure in the blackfoot disease endemic area have been focused on malignant tumors. We, therefore, conducted this study to analyze mortality of all death causes in blackfoot disease endemic areas and to determine other neglected cancers or noncancer diseases related to artesian well water containing high levels of arsenic. We calculated standardized mortality ratios for cancer and noncancer diseases, by sex, during the period from 1971 to 1994 and compared them to the local reference group (i.e, Chiayi-Tainan County) and the national reference group (i.e., Taiwan population). The results revealed marked standardized mortality ratio differences for the 2 reference groups. Greater mortality was found for males and females with bladder, kidney, skin, lung, nasal-cavity, bone, liver, larynx, colon, and stomach cancers, as well as lymphoma than in the local reference population. With respect to noncancer diseases, we found greater mortality for males and females who had vascular disease, ischemic heart disease, diabetes mellitus, and bronchitis than in the local reference group. Mortalities for other diseases--including rectal cancer, cerebrovascular disease, and other diseases--were higher among cases than the local reference group. Our results indicated that the hazardous effect of arsenic is systemic. Diseases related to arsenic exposure included those reported previously by other investigators, as well as diseases reported in the present study.

Exposure to fumes from cooking oils, when not reduced by an extractor, may be an important factor in causing lung cancer in non-smoking Taiwanese women.

MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein-coupled receptor kinase-interacting protein 1 (GIT1)-as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p-mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal-regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. Cancer Res; 74(3); 751-64. Ó2013 AACR.

Cigarette smoking cannot fully explain the epidemiologic characteristics of lung cancer in Taiwanese women, who smoke rarely but have lung cancer relatively often. In a previous study, the authors suspected that exposure to fumes from cooking oils was an important risk factor for lung cancer in Taiwanese women nonsmokers in the Republic of China. In a new case-control study conducted in 1993-1996, they further explored the association of oil fumes with lung cancer in women. Two sets of controls were used concurrently. The subjects were 131 nonsmoking incident cases with newly diagnosed and histologically confirmed primary carcinoma of the lung, 252 hospital controls hospitalized for causes unrelated to diseases of smoking, and 262 community controls; all controls were women nonsmokers matched by age and date of interview. Details on cooking conditions and habits were collected, in addition to other epidemiologic data. Lung cancer risk increased with the number of meals per day to about threefold for women who cooked these meals each day. The risk was also greater if women usually waited until fumes were emitted from the cooking oil before they began cooking (adjusted odds ratios = 2.0-2.6) and if they did not use a fume extractor (adjusted odds ratios = 3.2-12.2). These results suggest that a proportion of lung cancer may be attributable to the habit of waiting until the cooking oil has been heated to a high temperature before cooking the food.