Ken Chung Chen

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.

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.

α-Catulin knockdown induces senescence in cancer cells

Cellular senescence functions as a tumor suppressor that protects against cancer progression. α-Catulin, an α-catenin-related protein, is reported to have tumorigenic potential because it regulates the nuclear factor-κB (NF-κB) pathway, but little is known about its clinical relevance and the mechanism through which it regulates cancer progression. Here, we found that α-catulin mRNA levels were significantly upregulated in cancer cell lines and clinical oral squamous cell carcinomas, which positively correlated with tumor size (P=0.001) and American Joint Committee on Cancer (AJCC) stage (P=0.004). α-Catulin knockdown in the OC2 and A549 cancer cell lines dramatically decreased cell proliferation and contributed to cellular senescence, and inhibited OC2 xenograft growth. Mechanistic dissection showed that α-catulin depletion strongly induced the DNA-damage response (DDR) in both cell lines, via a p53/p21-dependent pathway in A549 cells, but a p53/p21-independent pathway in OC2 cells carrying mutant p53. Global gene expression analysis revealed that α-catulin knockdown altered cell-cycle regulation and DDR pathways at the presenescent stage as well as significantly downregulate several crucial genes related to mitotic chromosome condensation, DDR and DNA repair systems, which suggests that its depletion-induced cellular senescence might be caused by chromosome condensation failures, severe DNA damage and impaired DNA repair ability. Our study provides evidence that α-catulin promotes tumor growth by preventing cellular senescence and suggests that downregulating α-catulin may be a promising therapeutic approach for cancer treatment.

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.

Evaluation of mandibular contour in patients with significant facial asymmetry

Most previous studies on facial asymmetry have not specifically differentiated mandible deviation from structural asymmetry of the mandible. The purpose of this study was to assess the symmetry of the mandible by examining its contour in a cohort of patients with significant facial asymmetry. Eleven cases of facial asymmetry with chin deviation ≥10mm were enrolled. A voxel-paired median plane (optimal symmetry plane, OSP) and two landmark-based median planes were generated. The OSP was created by computing the best pairing of the bony voxels on the two sides. One side of the mandibular contour was mirrored onto the other side using the test plane. The contour differences were measured by distance and by area ratio. They were examined both in frontal and frontal downward inclined view. The contour symmetry of the mandible was that revealed by the plane that presented the best symmetry. The results showed that the OSP worked best in bisecting the contour into two symmetrical halves. Contour analysis showed relatively small discrepancies between the two sides. In conclusion, the mandibles retained an acceptable contour symmetry despite the presence of significant mandibular deviations. It is suggested that proper mandibular alignment be the primary objective in the correction of facial asymmetry.

Novel quantitative analysis of autofluorescence images for oral cancer screening

OBJECTIVES VELscope® was developed to inspect oral mucosa autofluorescence. However, its accuracy is heavily dependent on the examining physicians experience. This study was aimed toward the development of a novel quantitative analysis of autofluorescence images for oral cancer screening. MATERIALS AND METHODS Patients with either oral cancer or precancerous lesions and a control group with normal oral mucosa were enrolled in this study. White light images and VELscope® autofluorescence images of the lesions were taken with a digital camera. The lesion in the image was chosen as the region of interest (ROI). The average intensity and heterogeneity of the ROI were calculated. A quadratic discriminant analysis (QDA) was utilized to compute boundaries based on sensitivity and specificity. RESULTS 47 oral cancer lesions, 54 precancerous lesions, and 39 normal oral mucosae controls were analyzed. A boundary of specificity of 0.923 and a sensitivity of 0.979 between the oral cancer lesions and normal oral mucosae were validated. The oral cancer and precancerous lesions could also be differentiated from normal oral mucosae with a specificity of 0.923 and a sensitivity of 0.970. CONCLUSION The novel quantitative analysis of the intensity and heterogeneity of VELscope® autofluorescence images used in this study in combination with a QDA classifier can be used to differentiate oral cancer and precancerous lesions from normal oral mucosae.

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.

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.