Pei-Shan Ho

Malignant transformation of oral potentially malignant disorders in males: a retrospective cohort study.

BackgroundOral squamous cell carcinoma could be preceded by clinically evident oral potentially malignant disorders (OPMDs). Transformation of OPMDs to cancer has been studied in several population groups. It is difficult to undertake comparisons across populations due to variations in the methods of computation of malignancy rates among different studies. The aim of our study was to estimate the rate of malignant transformation of OPMDs taking into account the duration of follow-up and to identify the significant factors indicative of malignant potential.MethodsA total of 148 male patients with OPMDs were included. They were selected among all consecutive subjects registered at the maxillofacial clinic at a medical hospital in Kaohsiung, Taiwan. The mean follow up period was 37.8 months.ResultsThe malignant transformation rate was highest in subjects diagnosed with oral epithelial dysplasia. In this group the transformation rate was 7.62 per 100 persons-year. The rate in the group with verrucous hyperplasia (VH) was 5.21 per 100 persons-year, and in those with hyperkeratosis or epithelial hyperplasia was 3.26 per 100 persons-year. The anatomical site of OPMDs was the only statistically significant variable associated with malignancy. The hazard rate ratio (HRR) was 2.41 times for tongue lesions when compared with buccal lesions.ConclusionThe reported discrepancies of malignant transformation of OPMDs involve the follow-up time to cancer development and hence it is preferable to use a time-to-event estimation for comparisons. We found that malignant transformation of OPMDs involving the tongue was significantly higher than in other anatomical subsites after adjusting for the clinicopathological type or lifestyle factors at diagnosis.

Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role of Cyclooxygenase-2 −1195G>A Polymorphism Reveal Risk of Oral Cancer

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 gene-environment 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 -1195G>A polymorphism in these cell lines showed diverse inflammatory response (KB>>Ca9-22>SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-kappaB 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, 2.4 and 1.8, respectively), whereas the COX-2 -1195A/A homozygote presented a potential genetic risk (OR, 1.55). The strongest joint effect for OSCC was seen in betel chewers with -1195A/A homozygote (aOR, 79.44). In the non-betel chewing group, the -1195A/G and A/A genotypes together with the combined use of alcohol and cigarettes increased risk to 15.1-fold and 32.1-fold, respectively, compared with the G/G genotype without substance use. Taken together, these findings illustrate a valuable insight into the potential role of the COX-2 promoter region in contributing to the development of betel-related OSCC, including ANE/sANE-induced transcriptional effects and enhanced joint effects of COX-2 -1195A allele with substance use of ABC.

Risks of Exposure to Occupational Asthmogens in Atopic and Nonatopic Asthma: A Case-Control Study in Taiwan

RATIONALE Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy. OBJECTIVES We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function. METHODS We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (≥100 U/ml) or a positive Phadiatop test (≥0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix. MEASUREMENTS AND MAIN RESULTS We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8-8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6-4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8-21.8; and AOR, 4.1; 95% CI, 1.3-13.0, respectively). The ratio of FEV₁ to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma. CONCLUSIONS In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma.

Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

BackgroundIn Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.MethodsTaiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival.ResultsThe five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate.ConclusionOur study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.

Ingredients Contribute to Variation in Production of Reactive Oxygen Species by Areca Quid

Areca quid (AQ) chewing has been implicated an independent risk factor for the development of oral cancer. Taiwanese areca quid (AQ) refers to a combination of areca nut (AN), lime, and inflorescence of Piper betle Linn. (IPB) or Piper betle leaf (PBL). Studies of AQ in other countries reported that AN extract combined with lime generates reactive oxygen species (ROS), such as hydroxyl radical (HO·), known to be a contributing factor in oral mucosa damage. To determine whether HO· is formed in the oral cavity during AQ chewing, the formation of meta-tyrosine (m-Tyr) and ortho-tyrosine (o-Tyr) from l-phenylalanine (Phe) was confirmed. It was demonstrated that combined aqueous extracts of AN, lime, metal ions (such as Cu2+ and Fe2+), and IPB or PBL produced HO·. Thus, the yield of HO· significantly increases when higher amounts of IPB or lime are added and also when Cu2+ and Fe2+ are increased. Further, the omission of any one of these ingredients significantly reduces the formation of HO·. Our results found that chewing AQ with IPB generated significantly higher HO· than chewing AQ with PBL, and may result in greater oxidative damage to the surrounding oral mucosa. This study was supported by a grant from the Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung 807, Taiwan (NHRI-CN-IN-9006P).

CYP26B1 is a novel candidate gene for betel quid-related oral squamous cell carcinoma

Substantial epidemiological data suggest a role for environmental factors (for example, the use of alcohol, betel quid (BQ), and cigarettes) in the occurrence of oral squamous cell carcinoma (OSCC), but the evidence for the genes involved has been inconsistent. This study was to investigate the role of CYP26B1, together with the use of alcohol, BQ, and cigarettes, on BQ-related OSCC. The association study (247 OSCC cases and 338 controls) was conducted to examine the possible interplay between CYP26B1 polymorphisms and alcohol, BQ, and cigarettes use. Additional gene expression was evaluated between OSCC tissue and adjacent normal tissue. The genetic polymorphism AA of CYP26B1 appeared to correlate with the risk of OSCC (OR=2.26; 95% CI, 1.35-3.80). Chewing BQ multiplicatively interacted with CYP26B1 AA to increase the OSCC risk (aOR=70.04; 95% CI, 13.62-360.11). The independent risk of OSCC was observed among BQ chewers with CYP26B1 AA, and compared with chewers with the CYP26B1 CC genotype (stratified aOR=2.88; 95% CI, 1.07-7.74). Increased expression of CYP26B1 was observed in tumor tissue compared with adjacent normal tissue. The CYP26B1 gene plays a novel role in the BQ dependent pathogenesis of OSCC.

Comparing dose-response measurements of oral habits on oral leukoplakia and oral submucous fibrosis from a community screening program.

BACKGROUND Many studies have reported that the interaction and dose-response effects of betel quid chewing, tobacco smoking and alcohol drinking habits are important risk factors for oral cancer and precancerous lesions or conditions. These results are useful for comparing statistics, but may not be informative for personal disease-related information. METHODS This study used data from a community screening program to evaluate the dose-response effects of daily frequency and duration from oral habits in Taiwan. The receiver operating characteristic (ROC) curves were further used to compare exposure measurements on indicating the occurrence of lesions/conditions. RESULTS Our results showed that the highest prevalence was found in leukoplakia (11.1%) and followed by oral submucous fibrosis (OSF, 4.4%). Betel quid chewing habit was found to have dose-response effects on leukoplakia and OSF, cigarette smoking habit only has the dose-response effect on leukoplakia, and alcohol drinking was not associated with both oral precancers. The daily frequency of chewing habit is a better indicator than other dose-response measurements for the occurrence of precancers. In addition, the cut-off points of two to five counts per day have about 60-82% of sensitivities and 79-88% of specificities. CONCLUSIONS The cut-off points from ROC curves can provide an informative message to people with oral habits and their chances of developing diseases. High daily frequency of chewing can lead to excessive irritation to oral mucosa. Although the tobacco is never added to chewing quid in Taiwan, intensive irritation may play an important role in developing oral precancers in Taiwan.

Conditional survival rates of buccal and tongue cancer patients: How far does the benefit go?

The purpose of this study was to investigate the conditional survival probability in buccal and tongue cancer patients, and to identify the limit of increment in conditional survival probabilities after first diagnosis. This study retrospectively analyzed 339 consecutive patients with either buccal or tongue caner. The conditional survival probability was computed by Kaplan-Meier estimates, and the pair-wise Log-rank tests with Bonferroni correction were used to evaluate differences among conditional survival curves. It was found that the 3-year conditional survival rates for successive years of survival were 55.5%, 69.9%, 74.1% and 77.8%. The conditional survival curves started to become significantly better than the original survival curve at the twelfth month, and those curves after 24 months of survival were not significantly different from each other. Many previous studies have described the benefit of conditional survival probabilities for personalized information on better chance of survival, but only reported conditional survival probabilities and statistical tests for point-wise estimates. In this study, a new approach was adopted to conclude that the idea of conditional survival probability is best for the first 2 years in buccal and tongue cancer patients, and any longer survival time would not make significant difference in survival rates. The idea of pair-wise log-rank tests on conditional survival curves can provide statistical evidence for the critical time frame of survival in many different cancers.