Wei Ting Hsueh

Investigating the association between oral hygiene and head and neck cancer

OBJECTIVES This analysis examined the association between oral hygiene and head and neck cancer (HNC) and whether this association differed by the consumption of alcohol, betel quid, or cigarette and by the genetic polymorphisms of inflammation-related genes. MATERIALS AND METHODS Interviews regarding dental care and oral health were conducted with 317 HNC cases and 296 controls. Genotyping was performed for 6 single nucleotide polymorphisms in IL6, IL10 and PTGS2. RESULTS A positive association was observed between HNC and no regular dental visits (odds ratio (OR)=2.86, 95% confidence interval (CI): 1.47-5.57), brushing teeth <2times/day (OR=1.51, 95% CI: 1.02-2.23), frequent gum bleeding (OR=3.15, 95% CI: 1.36-7.28), and loss of >20 teeth (OR=2.31, 95% CI: 1.05-5.07). Analysis with dental care score (range: 0-4, 4=worst dental care), which combined regular dental visits, toothbrushing, and use of dental floss and mouthwash, showed a positive trend with HNC risk, particularly among alcohol drinkers and cigarette smokers. Multifactor dimensionality reduction analysis divided the study subjects into high- and low-risk group based on combinations of dental care score and IL6 rs1800796 genotypes. Compared to the low-risk group, the high-risk group had an OR of HNC=2.16 (95% CI: 1.44-3.25). CONCLUSIONS This study observed a positive association between poor oral hygiene and HNC, which appeared to differ by alcohol or cigarette consumption and the genotypes of IL6 rs1800796. Further investigations are needed to determine whether poor oral hygiene is a cause for HNC or a surrogatemarker of an unhealthy lifestyle that increases the risk of HNC.

The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer

Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol‐metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1 + *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non‐functional ALDH2 genotypes (*1/*2 + *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non‐functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.

Intensity-modulated radiotherapy improves outcomes in postoperative patients with squamous cell carcinoma of the oral cavity

OBJECTIVES We compared the outcomes and survival rates of patients with oral cavity squamous cell carcinoma receiving postoperative conventional radiotherapy (RT) or intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS From January 2005 to September 2008, medical records of 131 consecutive patients with oral cancer receiving postoperative radiotherapy in the Department of Radiation Oncology of National Cheng Kung University Hospital were reviewed. Patients were divided into two groups according to the administration of postoperative conventional RT or IMRT. The loco-regional control, survival, and other prognostic factors were compared. RESULTS The 3-year Kaplan-Meier estimates of overall survival for patients receiving conventional RT and IMRT groups were 51.2% vs. 69.4% (p=0.079), respectively. The 3-year local-regional control (53.5% vs. 76.3%; p=0.020) and disease-free survival rates (47.8% vs. 70.0%; p=0.027) were significantly increased in the IMRT group. This retrospective study also identified that extracapsular spreading, margin positive/close (≤ 2mm), more advanced T stage (T3-4 vs. T1-2), and conventional RT method were associated with worse prognosis. CONCLUSIONS The addition of chemotherapy to adjuvant radiotherapy is recommended in patients with above risk factors. Our result underscores that IMRT should be considered to apply to OSCC patients referred for postoperative treatment.

Allergies and Risk of Head and Neck Cancer: An Original Study plus Meta-Analysis

Background Although the relationship between allergy and cancer has been investigated extensively, the role of allergy in head and neck cancer (HNC) appears less consistent. It is not clear whether allergies can independently influence the risk of HNC in the presence of known strong environmental risk factors, including consumption of alcohol, betel quid, and cigarette. Methods The current paper reports results from: 1) an original hospital-based case-control study, which included 252 incident cases of HNC and 236 controls frequency-matched to cases on sex and age; and 2) a meta-analysis combining the results of the current case-control study and 13 previously published studies (9 cohort studies with 727,569 subjects and 550 HNC outcomes and 5 case-control studies with 4,017 HNC cases and 10,928 controls). Results In the original case-control study, we observed a strong inverse association between allergies and HNC [odds ratio = 0.41, 95% confidence interval (CI): 0.27–0.62]. The meta-analysis also indicated a statistically significant inverse association between HNC and allergies [meta-relative risk (RR) = 0.76, 95% CI: 0.63–0.91], particularly strong for allergic rhinitis (meta-RR = 0.55, 95% CI: 0.40–0.76). In addition, the inverse association between allergies and HNC was observed only among men (meta-RR = 0.67, 95% CI: 0.54–0.84) but not among women (meta-RR = 0.98, 95% CI: 0.81–1.18). Conclusions These findings suggest that immunity plays an influential role in the risk of HNC. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are warranted to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help devise effective strategies to reduce and treat HNC.

Tea Consumption and Risk of Head and Neck Cancer

Background The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage. Methods Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking. Results A reduced HNC risk associated with tea drinking (OR for every cup per day = 0.96, 95% CI: 0.93–0.99; OR for ≧5 cups per day = 0.60, 95% CI: 0.39–0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per day = 0.93, 95% CI: 0.88–0.98; OR for ≧5 cups per day = 0.32, 95% CI: 0.16–0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea. Conclusions This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC.

Investigating the Association between Alcohol and Risk of Head and Neck Cancer in Taiwan

Although alcohol is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature in several aspects. We analyzed detailed alcohol consumption data (amount and type of alcoholic beverage) of 811 HNC patients and 940 controls to evaluate the association between alcohol and HNC by HNC sites and by genotypes of ADH1B and ALDH2. Alcohol was associated with an increased HNC risk in a dose-response relationship, with the highest risk observed for hypopharyngeal cancer, followed by oropharyngeal and laryngeal cancers. Liquor showed a stronger positive association with HNC than beer and wine. The highest HNC risk occurred in individuals with the slow ADH1B and slow/non-functional ALDH2 genotype combination. In our study population, 21.8% of HNCs, 55.7% of oropharyngeal cancers, and 89.1% of hypopharyngeal cancers could be attributed to alcohol. Alcohol accounted for 47.3% of HNCs among individuals with the slow ADH1B and slow/non-functional ALDH2 genotype combination. The HNC risk associated with alcohol became comparable to that of never/occasional drinkers after ten or more years of cessation from regular alcohol drinking. In conclusion, alcohol use is associated with an increased HNC risk, particularly for individuals with slow ethanol metabolism. HNC incidence may be reduced by alcohol cessation.

A Comprehensive Analysis on the Association between Tobacco-Free Betel Quid and Risk of Head and Neck Cancer in Taiwanese Men.

Objectives Although betel quid (BQ) is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature regarding the dose-response, BQ types, HNC sites, and BQ cessation. The current study was conducted to fill these insufficiencies. Materials and Methods A hospital-based case-control study was conducted to evaluate the association between BQ and HNC. In-person interview was conducted to collect data on BQ chewing. The current analysis included 487 men newly diagnosed with HNC and 617 male controls who were frequency-matched to the cases by age. The association between BQ and HNC was assessed using multivariable unconditional logistic regression. Results Ever BQ chewing was associated with an increased HNC risk regardless of the BQ types. A non-linear positive association between BQ and HNC was observed, with a steep rise in HNC risk for the first 5 pack-years or 200,000 minutes of BQ consumption. Every year of BQ cessation was associated with a 2.9% reduction in HNC risk; however, the risk did not reduce to the level of non-BQ chewers even after 20 years of BQ cessation. Eliminating BQ chewing may prevent 51.6% of HNCs, 62.6% of oral cancers, and 41.3% of pharyngeal cancers in Taiwan. Conclusion Our results supported the positive association between BQ and HNC. BQ cessation is effective in reducing HNC risk and should be encouraged. Because BQ cessation may not reduce the HNC risk to the level of non-BQ chewers, it is important to prevent the initiation of BQ chewing.

Constitutive STAT5 activation correlates with better survival in cervical cancer patients treated with radiation therapy.

PURPOSE Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. METHODS AND MATERIALS A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. RESULTS Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor (≥ 4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. CONCLUSIONS This is the first report to provide the overall expression patterns and prognostic significance of specific STATs in cervical carcinoma. Our results indicate that constitutive STAT5 activation correlates with better metastasis-free survival and overall survival in cervical cancer patients who have received radiation therapy.

Alcohol Drinking Obliterates the Inverse Association Between Serum Retinol and Risk of Head and Neck Cancer.

AbstractThis analysis evaluated the association between serum retinol levels and risk of head and neck cancer (HNC) and whether the association is modulated by the use of alcohol, betel quid, or cigarette. In addition, we also examined the association between HNC risk and 2 single nucleotide polymorphisms, TTR rs1667255 and RBP4 rs10882272, that have been associated with serum retinol levels. Unconditional logistic regression was performed to evaluate the association between serum retinol levels and HNC risk among 160 HNC cases and 198 controls. The associations between TTR rs1667255 and RBP4 rs10882272 and serum retinol levels or HNC risk were evaluated by linear regression and unconditional logistic regression, respectively, for 418 HNC cases and 497 controls. The results showed that HNC cases had a lower mean serum retinol level compared with controls (845.3 &mgr;g/L vs 914.8 &mgr;g/L, P = 0.03). An inverse association between serum retinol levels and HNC risk occurred among never/occasional alcohol drinkers but not among regular drinkers. TTR rs1667255 was associated with serum retinol levels; however, neither TTR rs1667255 nor RBP4 rs10882272 was associated with HNC risk. In summary, this study showed an inverse association between serum retinol levels and HNC risk, specifically among never/occasional alcohol drinkers. More studies are needed to establish the underlying biologic mechanisms for the inverse association between serum retinol levels and HNC risk and the modulation of this relationship by alcohol drinking.

Investigating the association between diet and risk of head and neck cancer in Taiwan

Most studies reporting an inverse association between the consumption of vegetables and fruits and head and neck cancer (HNC) risk were conducted in Western populations and only a few included East Asians. The current case-control study investigated the association between diet and HNC risk using data of 838 HNC cases and 998 controls from a case-control study of HNC conducted in Taiwan. Each participant was asked about their consumption of fresh vegetables, pickled vegetables, fresh fruits, citrus fruits, meat, processed meat, fish, egg, and dairy products. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with each food category, adjusted for sex, age, education, and use of alcohol, betel quid and cigarette. An inverse association was observed between HNC risk and daily intake of fresh vegetables (OR = 0.44, 95% CI: 0.20-0.95, p-trend = 0.002) or fruits (OR = 0.55, 95% CI: 0.43-0.72, p-trend = 0.00001). Individuals who did not consume fresh fruits and vegetables daily had more than double the risk of HNC compared to those with daily intake of vegetables and fruits (OR= 2.24, 95% CI: 1.54-3.25). The results of the current study supported an inverse association between the consumption of fresh vegetables and fruits and HNC risk. In addition to cessation of cigarette smoking and betel quid chewing and reduction of alcohol drinking, a public health campaign for preventing the occurrence of HNC should promote a healthy diet that contains plenty of fresh vegetables and fruits.