Effects of direct-acting antiviral therapy for patients with advanced hepatocellular carcinoma and concomitant hepatitis C-A population-based cohort study.

OBJECTIVE: We analyzed real-world data to elucidate the effects of anti-Hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy on survival in patients with advanced hepatocellular carcinoma (HCC) and concomitant HCV infection treated with sorafenib. MATERIALS AND METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance Research Database and the Registration System for Patients Treated with Oral Hepatitis C Antivirals to identify patients with advanced HCC and concomitant HCV infection who received initial targeted therapy (sorafenib) in 2018-2019. The overall survival (OS) of the DAA and non-DAA groups were compared using the Kaplan-Meier survival analysis. Propensity score matching was performed using a ratio of 1:4 to reduce confounding between the DAA and non-DAA groups. RESULTS: The study included 1,684 patients (122 DAA and 1,562 non-DAA users) with HCC and concomitant HCV infection who used sorafenib for the first time in 2018-2019. The Kaplan-Meier survival analysis indicated that advanced HCC patients who used DAAs had longer OS compared to non-DAA patients. The mean survival times were 20.7 months for DAA and 12.5 months for non-DAA. Results obtained after propensity matching indicated a significant difference in OS between the DAA and non-DAA groups. CONCLUSIONS: The analysis of big data from the Taiwan National Health Insurance Research Database revealed that advanced HCC patients on sorafenib benefited from DAAs as a treatment for HCV infection. Patients whose HCV infection was cured had better OS.

Inhibitory effects of essential oils from Asteraceae plant against pathogenic fungi of Panax notoginseng.

AIMS: Diseases caused by pathogenic fungi was a major constrain in increasing productivity and improving quality of Panax notoginseng. The aim of this research was to evaluate the inhibitory activity of essential oils (EOs) from Asteraceae family, Chrysanthemum indicum and Laggera pterodonta, against pathogenic fungi of P. notoginseng. METHODS AND RESULTS: The antifungal activity was investigated using multiple methods, disclosing that the EOs from C. indicum and L. pterodonta are active against hypha growth of different fungi but with different degrees of potency. Checkerboard testing indicated that the combination of EOs with hymexazol had synergistic effect against Pythium aphanidermatum, and exhibited additive effects against bulk of targeted pathogenic fungi. Besides, we found that the baseline sensitivity of Fusarium oxysporum to L. pterodonta EOs was higher than those of C. indicum by means of mycelium growth rate method. Finally, the practicability of those EOs as plant pesticide was confirmed by in vivo model showing that EOs can significantly inhibit the occurrence of root rot of P. notoginseng caused by F. oxysporum. CONCLUSION: Those studies suggest that the EOs from C. indicum and L. pterodonta had the potential to develop into new pollution-free pesticides for the protection of precious Chinese herbal medicines. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided a new way of biological control for overcoming the frequent diseases occurrence of P. notoginseng.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Clinical application of total parenteral nutrition in patients with peritoneal carcinomatosis.

Cancer patients with terminal stage peritoneal carcinomatosis are often unable to eat, rendering total parenteral nutrition (TPN) as the only option to avoid starvation. In this retrospective study, we reviewed the medical records of 46 patients with peritoneal carcinomatosis and compared them to the records of 51 patients who had gastrointestinal malignancy without evidence of peritoneal carcinomatosis. The factors evaluated include demographic data, cause of primary malignancy, ascites formation, anthropometric measurements, laboratory tests, and outcome measurements as well as factors associated with greater than 90-day survival. In-hospital mortality was observed in 31 of the 46 patients with peritoneal carcinomatosis, with a median survival time of 40 days (4-148 days) for all 46 patients. The median duration of TPN administration in the peritoneal carcinomatosis group was 24.1 ± 27.4 days (3-68 days). Severe infection related to TPN application was seen in 5/46 (10.7%) patients with peritoneal carcinomatosis and 6/51 (9.8%) patients without peritoneal carcinomatosis. The length of survival varied widely among terminal patients with peritoneal carcinomatosis. The average survival time in peritoneal carcinomatosis patients receiving TPN was short, indicating that the nutrition support of TPN was relatively suboptimal. Ascites was not a prognostic factor for peritoneal carcinomatosis, while body mass index was a predictor for 90-day survival.

A pilot study evaluating the clinical and immunomodulatory effects of an orally administered extract of Dendrobium huoshanense in children with moderate to severe recalcitrant atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder for which few safe and effective systemic treatments are available. To test the clinical and immunomodulatory effects of a crude polysaccharide fraction isolated from Dendrobium huoshanense for the treatment of AD, we conducted a pilot, uncontrolled case series study. Twenty-seven patients aged 4-18 years (mean∓SD, 10.82±4.4) with AD that had not responded to topical therapy were treated with polysaccharide derived from D. huoshanense for 4 weeks and followed-up for another 4 weeks. Progression of AD was determined with the Lund-Browder chart for children, the Investigator's Global Atopic Dermatitis Assessment (IGADA), and the Scoring Atopic Dermatitis (SCORAD) at weeks 0, 2, 4, and 8. Serum levels of cytokines were evaluated. Safety was determined with laboratory and clinical tests. The lesion area, IGADA score, total SCORAD result, and score for sleeplessness decreased significantly from weeks 0 to 4, but did not change significantly between weeks 4 and 8. The scores for subjective symptoms and pruritus decreased significantly from week 0 to week 4 and increased significantly from week 4 to week 8. Serum levels of IL-5, IL-13, IFN-gamma, and TGF-beta1 decreased significantly between weeks 0 and 4 and between weeks 0 and 8. No significant difference in the levels of IL-10 was found. The polysaccharide from D. huoshanense reduced the levels of some cytokines associated with AD and had beneficial effects on symptoms. No serious adverse effects occurred when it was administered orally for 4 weeks.

Chromium supplementation enhances insulin signalling in skeletal muscle of obese KK/HlJ diabetic mice.

AIM: Chromium is an essential nutrient required for glucose and lipid metabolism. Laboratory and clinical evidences indicate that chromium supplementation may improve insulin sensitivity by enhancing intracellular signalling. Considerable evidence suggests that serine phosphorylation of insulin receptor substrate 1 (IRS1) at 307 residue (IRS1-Ser307) inhibits insulin signalling and results in peripheral insulin resistance. Therefore, we investigated whether chromium-associated insulin action was mediated by modulation of IRS1-Ser307 phosphorylation. METHODS: Male KK/HlJ mice (genetically obese and insulin resistant) were supplemented daily with chromium-containing milk powder or placebo for 7 weeks. In analysing functionally characterized insulin resistance, the changes of blood biochemicals, inflammatory factors and insulin signalling molecules in skeletal muscle were analysed. RESULTS: Using KK mice model, we demonstrated that daily supplementation of trivalent chromium-containing milk powder reduced serum levels of glucose, insulin and triglycerides, and improved glucose and insulin tolerance. Mechanistic study showed that chromium supplementation activated postreceptor insulin signalling such as increasing IRS1, IRS1 tyrosine phosphorylation, p85alpha regulatory subunit of phosphatidylinositol 3-kinase and glucose transporter 4 expression, stimulating Akt activity, downregulating c-Jun N-terminal kinase (JNK) activity and decreasing IRS1 ubiquitinization and insulin resistance-associated IRS1 phosphorylation (IRS1-Ser307) in skeletal muscle. In addition, chromium supplementation attenuated pro-inflammatory cytokine expression in both blood circulation and skeletal muscle. CONCLUSION: Our data suggest that chromium-containing milk powder supplementation can provide a beneficial effect in diabetic subjects by enhancing insulin signalling in skeletal muscle. The improvement in insulin signalling by chromium was associated with the decreased IRS1-Ser307 phosphorylation, JNK activity and pro-inflammatory cytokine production.

Effects of surface electrical stimulation on the muscle-tendon junction of spastic gastrocnemius in stroke patients.

PURPOSE: The purpose of this study was to explore the effects of spasticity suppression by surface electrical stimulation (ES) o the muscle-tendon junction of spastic gastrocnemius muscles in stroke. METHODS: Twenty-four neurologically stable stroke patients (aged 41-69 years, 12-35 months post-stroke), with spasticity graded 2 or 3 on the modified Ashworth scale, were recruited and divided into two groups. In the ES group, each patient received 20 min of surface ES once daily, 6 days per week for 1 month. In the control groups, ES was used with stimulation intensity kept at zero. To evaluate the therapeutic effect, the modified Ashworth scale, Fmax/Mmax ratio, H-reflex latency, H-reflex recovery curve, and the 10-m walking time were tested before and after the 1-month of treatment. RESULTS: In the ES group, the modified Ashworth scale showed a trend toward reduced spasticity after 1 month of treatment. The Fmax/Mmax ratio decreased from 8.10% +/- 4.84% to 4.00% +/- 1.36%; the H-reflex latency increased from 28.87 +/- 2.45 ms to 29.40 +/- 2.57 ms; the H-reflex recovery curves indicated a downward shift; and the 10-metre walking time significantly decreased after ES. In the control group, none of the measures showed a statistically significant change. CONCLUSIONS: In this study, we demonstrated a way to suppress spasticity at a metameric site and to increase walking speed effectively by applying surface ES on the muscle-tendon junction of spastic gastrocnemius muscles.

Risk of betel chewing for oesophageal cancer in Taiwan.

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

Tobacco, betel quid, alcohol, and illicit drug use among 13- to 35-year-olds in I-Lan, rural Taiwan: prevalence and risk factors.

OBJECTIVES: This study determined the prevalence of and risk factors for substance use among rural Taiwanese. METHODS: We used a survey of a representative sample of 6318 participants aged 13 to 35 years in I-Lan, Taiwan, in 1996 through 1997. RESULTS: Perceived use of illicit drugs by peers, tobacco smoking, betel quid chewing, and male gender were the strongest predictors of illicit drug use. The prevalence of illicit drug use ranged from 0.3% among those who did not use any other substance to 7.1% among those using tobacco, betel quid, and alcohol. CONCLUSIONS: Preventive measures should address substance use in general rather than aiming at single substances.

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Bloodletting acupuncture of the engorged vein around Bl-40 (Wei-Chung) for acute lumbar sprain.

Bloodletting acupuncture is one of the most classic methods of acupuncture therapy, and is still popularly used to treat acute lumbar sprain in the oriental world. However, most physicians in the western world are not familiar with bloodletting acupuncture, though they may know ordinary acupuncture well. Furthermore based on the literature reviewed, there have been few studies which have investigated the effect of bloodletting acupuncture upon acute lumbar sprain. In this study, we tried to determine if bloodletting acupuncture is effective for acute lumbar sprain. In total, twelve patients were enrolled for analysis. Five patients were treated with ordinary acupuncture upon the contralateral SI-3 (Hou-Hsi) point alone. Seven patients were first treated with bloodletting acupuncture to the engorged vein around the ipisilateral Bl-40 (Wei-Chung), and then followed by ordinary acupuncture upon the contralateral SI-3. It was demonstrated that bloodletting acupuncture to the engorged vein around the ipisilateral Bl-40 followed by ordinary acupuncture upon the contralateral SI-3 had more pain relief than ordinary acupuncture upon the contralateral SI-3 alone (83 +/- 23% vs. 44 +/- 28%) (P < 0.01). And bloodletting acupuncture to the engorged vein around the ipisilateral Bl-40 decreased pain by 56 +/- 23%, similar to that of ordinary acupuncture upon the contralateral SI-3 alone (44 +/- 28%). These findings suggest that bloodletting acupuncture to the engorged vein around the ipisilateral Bl-40 (Wei-Chung) has a substantial contribution for treatment of acute lumbar sprain.

Gliotoxic action of glutamate on cultured astrocytes.

Because of the well-documented importance of glutamate clearance by astrocytes in protecting neurons against excitotoxicity, it was interesting to examine whether L-glutamate exerts a toxic action on cultured astrocytes. Cell damage was evaluated by measuring activity of lactate dehydrogenase (LDH) released into the culture medium. Exposure of astrocyte cultures of the neonatal rat cerebral cortex to L-glutamate resulted in a concentration- and time-dependent increase in the release of LDH. L-Glutamate-induced gliotoxicity appeared to be mediated predominantly by the increase of oxidative stress because the reduced glutathione content and its effects were almost completely blocked by vitamin E and pyrrolidinedithiocarbamate. To support this notion further, the supplementation or depletion of intracellular reduced glutathione content attenuated or worsened L-glutamate toxicity, respectively. Activation of the glutamate transporter mimicked the action of L-glutamate on astrocytes. In addition, degrees of cell damage were not directly correlated to the levels of glutamate uptake. Moreover, the mechanism of this toxicity required energy and macromolecular synthesis. Taken together, brief exposure to L-glutamate resulted in glutamate uptake and cell swelling, whereas sustained exposure injured astrocytes via oxidative stress instead of the excitatory mechanism.

KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms arising in the gastrointestinal tract. GISTs express the KIT receptor tyrosine kinase, and many cases have activating mutations in the KIT juxtamembrane region. We now report an analysis of KIT cDNA and genomic sequences in eight GISTs that lack juxtamembrane region mutations. Six cases contained heterozygous exon 9 mutations in which six nucleotides, encoding Ala-Tyr, were duplicated. The other two cases contained homozygous exon 13 missense mutations, resulting in substitution of Glu for Lys(642), that were associated with constitutive KIT tyrosine phosphorylation. Sequence analysis of DNAs from nonneoplastic companion tissues revealed that both the exon 9 and exon 13 mutations were somatic. These are the first descriptions, in any tumor, of mutations in KIT exons encoding the C-terminal end of the extracellular domain and the first part of the split kinase domain. These findings indicate that KIT may be activated by mutations in at least three domains-extracellular, juxtamembrane, and kinase-in GISTs.

Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1.

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.

Knowledge and perception of oral health promotion in schools among dental nurses in Sarawak, Malaysia.

In recent years, the concept of a Health-Promoting School has received much interest. In Malaysia, dental nurses are ideally placed to play a lead role in promoting Oral Health within the school setting. This study aims to provide information on the knowledge, perception and perceived role of Oral Health Promotion in schools, among dental nurses. A postal questionnaire was used to measure dental nurses' knowledge, perception and perceived role of Oral Health Promotion. The majority (60%) of dental nurses had good knowledge of Oral Health Promotion. Generally, they perceived that they play an important role in promoting Oral Health in schools. However, a sizeable proportion (25%) did not think they had a role to play in working together with school authorities to provide children with healthy food choices in school canteens. The majority (60%) of dental nurses did not perceive Oral Health Promotion to be important as a whole. They had a good perception of the concepts: it supports behaviour change, it has appropriate goals, it integrates oral health and general health and relieves anxiety. However, they had a poorer perception of the concepts; diverse educational approaches, participation, focus on prevention, early intervention, "spread of effect" of dental health education and "make healthier choices the easier choices". Years of service was not significantly associated with knowledge and perception of Oral Health Promotion. Dental nurses should be reoriented towards a more holistic practice of Oral Health Promotion. Workshops that invite active participation from dental nurses should be conducted to equip them with the necessary knowledge and skills.

Transmission of hepatitis C virus in Taiwan: prevalence and risk factors based on a nationwide survey.

A nationwide community-based survey on hepatitis C virus (HCV) was carried out in seven townships in Taiwan. A total of 11,904 men aged 30-64 years were recruited for testing for antibodies against HCV (anti-HCV) by second-generation enzyme immunoassay. A total of 272 seropositive cases and 282 seronegative controls were interviewed to explore risk factors for HCV infection in the study areas. Spouses of 214 seropositive cases were identified to assess the concordance of seropositivity of anti-HCV between spouses; genotypes of HCV were also tested in 26 couples who were both seropositive. A significant geographic variation in seroprevalence of anti-HCV was observed in the study townships (1.6-19.6%). Blood transfusions, medical injections, acupuncture and tattooing were related to an increased anti-HCV seroprevalence showing multivariate-adjusted odds ratios of 8.6, 2.5, 3.1, and 2.2, respectively, with corresponding population attributable risk percentages of 25%, 57%, 16%, and 3%, respectively. The anti-HCV prevalence in spouses of index cases (24%) was significantly higher than that observed in the general population of the study areas (4%). However, a striking interspousal discrepancy in HCV genotypes (20/26 = 77%) was observed among both seropositive couples. Common exposures to medical injections and acupuncture were reported by 15 (58%) of these couples. This study identified some endemic areas of HCV infection in Taiwan. Iatrogenic factors were common vehicles for HCV infection, and a concordance of anti-HCV seropositivity between spouses may primarily be due to extrafamilial iatrogenic infectious sources in study areas.

Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection.

Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.

Acupuncture treatment of urticaria.

Acupuncture has long been used to treat urticaria in the Asian world. Acute urticaria can be easily and effectively treated with acupuncture. L111 (Quchi), Sp10 (Xuehai), Sp6 (Sanyinjiao), and S36 (Zusanli) are the 4 acupuncture points most commonly prescribed. Chronic urticaria is a challenge for medical therapy. There are at least 6 kinds of acupuncture methods developed to overcome this challenge. The combination of ordinary acupuncture and auricular acupuncture has been observed to be a highly effective cure of chronic urticaria. Acupuncture point injection with thiamine hydrochloride (vitamin B1) is also an effective treatment. However, results of these clinical observations have not been systematically confirmed for lack of a control group and the need for standard classification of urticaria. Although these observational results have clinical limitations, they do offer insight into an alternative to conventional treatment of urticaria. In the future, acupuncture or acupuncturelike techniques may provide an effective alternative for treatment of patients with urticaria, particularly those refractory to medication therapy.

Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer.

Both genetic and environmental factors are involved in the development of cancer; some phase I and II enzymes involved in the metabolism of carcinogens are polymorphic in genotypes. This case-control study focused on the interactions between oral cancer risk factors and genetic polymorphisms of cytochrome P-450 (CYP) 2E1 and glutathione S-transferase (GST) M1 and GSTT1. A total of 41 male oral cancer cases was recruited from National Taiwan University Hospital, and 123 healthy controls frequency-matched on ethnicity, sex, and age were recruited from residents living in Taipei City and Taipei County. History of cigarette smoking, alcohol drinking, and betel quid chewing was obtained through a standardized questionnaire interview, and genotypes of CYP2E1, GSTM1, and GSTT1 were determined by PCR. Cigarette smoking, alcohol drinking, and betel quid chewing were significantly associated with the risk of oral cancer in a dose-response relationship. All betel quid chewers smoked cigarettes in both the case and control groups. In the multiple logistic regression analysis, those who had null genotypes of GSTM1 and/or GSTT1 had an increased oral cancer risk compared with those who had non-null genotypes of both GSTM1 and GSTT1, showing a multivariate-adjusted odds ratio (OR) of 4.6 with a 95% confidence interval (CI) of 0.9-23.7 (P = 0.08). The CYP2E1 c1/c2 and c2/c2 genotypes were associated with a significantly increased oral cancer risk compared with the c1/c1 genotype among those who did not chew betel quid (OR, 4.7; 95% CI, 1.1-20.2), but not among betel quid chewers. Habitual alcohol drinking was associated with a significantly increased oral cancer risk, showing an OR of 3.0 (95% CI, 1.1-8.8). These results implied that there are gene-gene and gene-environment interactions in the development of oral cancer.