The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer.

The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects.

Family cancer history and susceptibility to oral carcinoma in Puerto Rico.

BACKGROUND: Use of alcohol and tobacco are the major risk factors for cancers of the oral cavity and pharynx in most of the world. A heritable component to oral carcinoma risk also has been suggested, although only limited data are available on familial aggregation of this disease. METHODS: A population-based case-control study of 342 subjects with carcinomas of the oral cavity and pharynx (oral carcinoma) and 521 controls was conducted in Puerto Rico. The relation between family history of carcinomas of the oral cavity, the upper aerodigestive tract (UADT), and other selected sites with risk of oral carcinoma was explored using logistic regression modeling techniques. RESULTS: Risk of oral carcinoma was elevated for subjects reporting a first-degree relative with carcinoma of the oral cavity (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.8-8.0) or any UADT carcinoma (OR, 2.6; 95% CI, 1.4-4.8). The increased risk associated with family history of UADT carcinoma tended to be greatest for subjects with known risk factors (i.e., heavy consumption of alcohol and/or tobacco and infrequent intake of raw fruits and vegetables) and with oral carcinoma diagnoses at ages younger than 65 years. CONCLUSIONS: These findings are consistent with a heritable component to oral carcinoma, although shared lifestyle risk factors may be partially involved.

Comorbidity and survival of elderly head and neck carcinoma patients.

BACKGROUND: Alcohol and tobacco, the primary etiologic agents for head and neck carcinoma (HNCA), cause other chronic diseases and may contribute to the high prevalence of comorbid conditions and generally poor survival of persons with HNCA. METHODS: The authors explored the prognostic role of comorbidity in persons with HNCA using Health Care Finance Administration Medicare (HCFA) files linked with the appropriate files of the Surveillance, Epidemiology, and End Results (SEER) Program. The Charlson comorbidity index was applied to in-patient data from the HCFA files. The SEER data were used to ascertain survival and identify persons with HNCA diagnosed from 1985 to 1993 (n = 9386). RESULTS: In a proportional hazards regression model adjusted for age and historic stage at diagnosis, race, gender, marital status, socioeconomic status, histologic grade, anatomic site, treatment, and pre-1991 diagnosis, Charlson index scores of 0, 1, and 2+ had estimated relative hazards (RHs) with 95 confidence intervals (CIs) of 1.00, 1.33 (95% CI, 1.21-1.47), and 1.83 (95% CI, 1.64-2.05), respectively (P value for trend < 0.0001). The adjusted RH for a Charlson index score of 1 or more compared with 0, using stratified models, was found to be greater in whites (RH, 1.55; 95% CI, 1.43-1.67) than blacks (RH, 1.24; 95% CI, 0.96-1.60), local (RH, 1.72; 95% CI, 1.50-1.96) versus distant stage (RH, 1.25; 95% CI, 1.00-1.56), and age 65-74 years (RH, 1.53; 95% CI, 1.38-1.69) versus age 85+ years (RH, 1.42; 95% CI, 1.09-1.84). CONCLUSIONS: This study establishes comorbidity as a predictor of survival in an elderly HNCA population and lends support to the inclusion of comorbidity assessment in prognostic staging of patients with HNCA diagnosed after 65 years of age.

Mouthwash in the etiology of oral cancer in Puerto Rico.

OBJECTIVES: To determine if the risk of cancers of the mouth and pharynx is associated with mouthwash use in Puerto Rico, an area of relatively high risk. METHODS: Interviews were conducted with 342 cases of oral and pharyngeal cancer registered in Puerto Rico and diagnosed between 1992 and 1995 and with 521 population-based controls regarding mouthwash use and other factors. Mouthwash-related risks were estimated using unconditional logistic regression controlling for potential confounders. RESULTS: The adjusted odds ratio associated with using mouthwash with an alcohol content of 25% or greater was 1.0. Risks were not higher with greater frequency, years of use, or lifetime mouthwash exposure. Among tobacco and alcohol abstainers the odds ratio associated with mouthwash use was 2.8 (CI = 0.8-9.9), in contrast to 0.8 (CI = 0.4-1.7) and 0.9 (CI = 0.6-1.3) among those with light and heavy cigarette smoking/alcohol drinking behaviors, respectively. CONCLUSIONS: There was no overall increased risk of oral cancer associated with mouthwash use. An elevated, but not statistically significant, risk was observed among the small number of subjects who neither smoked cigarettes nor drank alcohol, among whom an effect of alcohol-containing mouthwash would be most likely evident. Our findings indicate the need to clarify the mechanisms of oral carcinogenesis, including the possible role of alcohol-containing mouthwash.

Tobacco use and oral disease.

Tobacco use is a risk factor for oral cancer, oral mucosal lesions, periodontal disease and impaired healing after periodontal treatment, gingival recession, and coronal and root caries. Available evidence suggests that the risks of oral diseases increase with greater use of tobacco and that quitting smoking can result in decreased risk. The magnitude of the effect of tobacco on the occurrence of oral diseases is high, with users having many times the risk of non-users. There is a clear benefit to quitting tobacco use. The risks of oral cancer and periodontal disease decline as time from cessation increases, and some oral mucosal lesions may resolve with cessation of smokeless tobacco use. Smoking accounts for half of periodontal disease and three-fourths of oral cancers in the United States. Because tobacco accounts for such a high proportion of these diseases, comprehensive tobacco control policies are required to make progress in reducing the burden of tobacco-related oral diseases. Effective treatments to prevent tobacco use and increase cessation are available and need greater implementation. Dental practices may provide a uniquely effective setting for tobacco prevention and cessation.

Associations between serum antibody levels to periodontal pathogens and early-onset periodontitis.

BACKGROUND: The role of antibodies to periodontal microorganisms in the development of periodontal tissue destruction is still unclear. The aim of this study was to investigate the association between serum levels of IgG, IgA, and IgM antibodies to 6 periodontal microorganisms and clinical subtypes of varying severity of early-onset periodontitis (EOP) in young African American adults. METHODS: The study group consisted of 159 African Americans aged 19 to 25 years (mean 22 years) and included 97 cases with EOP and 62 controls with no clinical signs of EOP. These subjects were selected from a nationally representative sample of adolescents who received an oral examination as part of the National Survey of Oral Health of United States Children in 1986-1987. The group was examined clinically a second time 6 years later and blood samples were collected. Serum levels of IgG, IgA, and IgM reactive to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, and Fusobacterium nucleatum were assessed. RESULTS: Serum levels of IgG and IgA antibody reactive to P. gingivalis and A. actinomycetemcomitans and IgA antibody to P. intermedia were significantly higher in generalized EOP cases compared to healthy controls. IgM antibody levels did not show any significant associations with EOP for any of the 6 bacterial species tested. There were no significant differences in antibody levels between controls and the 13 subjects in our study who were classified with localized EOP. CONCLUSIONS: The findings suggest that antibodies to P. gingivalis, P. intermedia, and A. actinomycetemcomitans may play a significant role in the pathogenesis of EOP. Substantial longitudinal studies that monitor antibody levels and avidity prior to disease onset, during progression, and following clinical intervention will be necessary to fully understand the role of this component of the immune response in protection versus tissue destruction and the potential use in EOP risk assessment and disease management.

Head and neck in situ carcinoma: incidence, trends, and survival.

This analysis describes the epidemiology of in situ head and neck carcinomas (anatomic sites of lip, oral cavity, pharynx, larynx) about which there is limited knowledge. Data were derived from nine population-based cancer registries participating in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. SEER annual age-adjusted incidence rates for in situ head and neck carcinomas increased from 6.33/1,000,000 person-years (PY) in 1976 to 8.04/1,000,000 PY in 1995 [percent change (PC)=35%, P<0. 001]. From 1976 to 1995 age-adjusted changes in incidence by anatomic site ranged from 53% PC (larynx) to -11% PC (lip) (both P<0. 005). Incidence and survival associated with in situ head and neck carcinomas varied by anatomic site, age, sex, and race and did so in a pattern similar to that seen for invasive carcinomas of this region. However, the climbing incidence of in situ carcinoma, which may be related to increased surveillance, contrasts sharply with the declining incidence of invasive carcinoma.

Self-collection of oral epithelial cell DNA under instruction from epidemiologic interviewers.

Oral epithelial cells provide an easily accessible source of germline DNA. Two methods for collection were compared in a 1992-1995 case-control study of oral cancer in Puerto Rico. One group of subjects (55 controls without oral cancer) collected oral rinse samples at home or work under the direction of a nonmedically trained interviewer ("self-collection"); the other group (94 controls) participated in a clinic-based collection, which also included blood and urine samples, conducted by a medical technician ("clinic collection"). Participation was higher for self-collection (98.2%) than for clinic collection (70.7%) (p < 0.001). DNA yields ranged from 2.0 to 204.5 microg (median, 25.9 microg) and did not differ by collection method, although yields varied by interviewer among self-collected samples (p = 0.02). Success rates for polymerase chain reaction amplification of the ADH3, NAT1, and multiplex CYP1A1/GSTT1/GSTM1 genotyping assays ranged from 76.4% (NAT1) to 98.2% (ADH3) for self-collected samples and were similar to those for clinic-collected samples (87.2-97.9%). Failure to amplify was associated with low DNA content (p = 0.015). Similar results were observed among cases (91 self-collected, 66 clinic collected), except that DNA yields did not vary by interviewer and a larger fraction (10.2%) of samples contained less than 5 microg of DNA, perhaps because of disease-related oral impairment. Self-collection of oral epithelial DNA samples appears satisfactory and efficient for many epidemiologic studies.

Cigar, pipe, and cigarette smoking as risk factors for periodontal disease and tooth loss.

BACKGROUND: Our purpose was to test the hypotheses that cigar and pipe smoking have significant associations with periodontal disease and cigar, pipe, and cigarette smoking is associated with tooth loss. We also investigated whether a history of smoking habits cessation may affect the risk of periodontal disease and tooth loss. METHODS: A group of 705 individuals (21 to 92 years-old) who were among volunteer participants in the ongoing Baltimore Longitudinal Study of Aging were examined clinically to assess their periodontal status and tooth loss. A structured interview was used to assess the participants' smoking behaviors with regard to cigarettes, cigar, and pipe smoking status. For a given tobacco product, current smokers were defined as individuals who at the time of examination continued to smoke daily. Former heavy smokers were defined as individuals who have smoked daily for 10 or more years and who had quit smoking. Non-smokers included individuals with a previous history of smoking for less than 10 years or no history of smoking. RESULTS: Cigarette and cigar/pipe smokers had a higher prevalence of moderate and severe periodontitis and higher prevalence and extent of attachment loss and gingival recession than non-smokers, suggesting poorer periodontal health in smokers. In addition, smokers had less gingival bleeding and higher number of missing teeth than non-smokers. Current cigarette smokers had the highest prevalence of moderate and severe periodontitis (25.7%) compared to former cigarette smokers (20.2%), and non-smokers (13.1%). The estimated prevalence of moderate and severe periodontitis in current or former cigar/pipe smokers was 17.6%. A similar pattern was seen for other periodontal measurements including the percentages of teeth with > or = 5 mm attachment loss and probing depth, > or = 3 mm gingival recession, and dental calculus. Current, former, and non- cigarette smokers had 5.1, 3.9, and 2.8 missing teeth, respectively. Cigar/pipe smokers had on average 4 missing teeth. Multiple regression analysis also showed that current tobacco smokers may have increased risks of having moderate and severe periodontitis than former smokers. However, smoking behaviors explained only small percentages (<5%) of the variances in the multivariate models. CONCLUSION: The results suggest that cigar and pipe smoking may have similar adverse effects on periodontal health and tooth loss as cigarette smoking. Smoking cessation efforts should be considered as a means of improving periodontal health and reducing tooth loss in heavy smokers of cigarettes, cigars, and pipes with periodontal disease.

Chewing tobacco use and dental caries among U.S. men.

BACKGROUND: Chewing tobacco has high levels of sugars and may be cariogenic, but few studies have investigated such an association. This study examined the relationship between chewing tobacco use and dental caries among U.S. adult men. METHODS: Participants in the Third National Health and Nutrition Examination Survey conducted from 1988 to 1994 were interviewed about tobacco use and examined by dentists. The authors included in their analysis dentate men 18 years of age or older. They calculated the mean number of decayed or filled permanent teeth, or DFT, and decayed or filled coronal tooth surfaces, or DFS, as well as the mean number and percentage of decayed or filled root surfaces, or RDFS, and decayed root surfaces, or RDS, by tobacco-use status. They used multiple logistic regression to examine the association between chewing tobacco use and root-surface caries. RESULTS: Men who currently used only chewing tobacco had a higher adjusted mean number of DFT than did those who currently used only snuff, only cigarettes or more than one form of tobacco or who never used tobacco. Mean DFS also was higher among chewing tobacco users than among those who used only snuff, only cigarettes or more than one form of tobacco. Chewing tobacco users had a higher mean RDFS and RDS than did the users of other forms of tobacco or nonusers. Current users of chewing tobacco were more than four times as likely as those who never used tobacco to have one or more RDFS or RDS, with a dose-response relationship between number of packages used per week and odds of having root-surface caries. CONCLUSIONS: In addition to its established role as a carcinogen, chewing tobacco may be a risk factor in the development of root-surface caries and, to a lesser extent, coronal caries. This may be due to high sugar content, increased gingival recession and enhanced collagenase activity. CLINICAL IMPLICATIONS: Interventions by dentists and other members of the oral health care team to prevent tobacco use and help users quit can reduce the risk of developing oral and systemic disease.

Tobacco and alcohol use and oral cancer in Puerto Rico.

OBJECTIVES: To determine risk for oral cancer in Puerto Rico associated with use of alcohol and tobacco. METHODS: In Puerto Rico, alcohol and tobacco use were compared among nonsalivary gland cancers of the mouth and pharynx (n = 342), cancers of major and minor salivary glands (n = 25) and 521 population-based controls. RESULTS: Alcohol (usual use, Ptrend < 0.0001 for men and Ptrend = 0.02 for women) and tobacco (usual use, Ptrend < 0.0001, for both men and women) were strong independent risk factors for oral cancer in Puerto Rico, with a multiplicative effect from combined exposures. Risks did not vary systematically by use of filter vs. nonfilter cigarettes. Risks with use of other forms of smoked tobacco were about sevenfold among both men and women. Risks decreased only gradually after cessation of tobacco and alcohol use. Tobacco use, but not alcohol, was linked to cancers of the salivary glands. The burden of oral cancer due to alcohol and tobacco use in Puerto Rico (76% for men, 52% for women) agreed closely with earlier estimates for the mainland US population, while about 72% of salivary gland cancer (men and women, combined) was due to tobacco use. CONCLUSIONS: Excess risks for oral cancer in Puerto Rico are largely explained by patterns of alcohol and tobacco use. Smoking filter vs. nonfilter cigarettes does not alter risk, while cessation of alcohol and tobacco use appears to reduce risk only gradually.

Motherhood during the teen years: a developmental perspective on risk factors for childbearing.

The role of peer relations in childhood and behavioral and family characteristics in early adolescence as risk factors for adolescent childbearing was investigated. Sociometric surveys across third, fourth, and fifth grade and parent and child measures of behavioral and family functioning at sixth and eighth grade were collected in a lower income, urban sample of 308 African American females. Results replicated earlier findings on the role of childhood aggression as a predictor of teen motherhood. In addition, girls who displayed stable patterns of childhood aggression were at significantly higher risk not only to have children as teenagers but to have more children and to have children at younger ages. Results also indicated that females who were depressed in midadolescence were at greater risk to become parents between age 15 and 19 years. These findings demonstrate the need to take a differentiated approach to understanding teen childbearing and varying developmental pathways in the prediction of teen motherhood.

Periodontal disease estimates in NHANES III: clinical measurement and complex sample design issues.

OBJECTIVE: This paper evaluates the possibility that examiner bias or other factors contributed to an observed decline in pocket depth and gingivitis between the two three-year sequential periods of time (or phases) covered by the Third National Health and Nutrition Examination Survey (NHANES III). METHODS: Prevalences of periodontal conditions were analyzed using data from two sets of repeat oral health examinations by examining dentists of NHANES III sample persons. The first set includes sample persons who were examined twice by the same examining dentist at an interval of one to six weeks. The second set includes sample persons who were assessed on the same day by both an examining dentist and a reference dentist. Other possible sources of error also were evaluated. RESULTS: Overall kappa statistics measuring agreement between or within dental examiners were within the range observed for other periodontal disease surveys. While differences were found among dentists in the prevalence of pocket depth of 4 mm or more, for each group of sample persons assessed by a reference examiner-examining dentist pair, the reference examiner's periodontal measurements closely corresponded to measurements made by the examining dentists. CONCLUSIONS: Differences between dental examiners in prevalences of periodontal conditions may be due in part to the fact that examinees were not randomly assigned to examiners. As a result, the sample persons examined by each dentist may not have been alike in characteristics thought to affect periodontal disease status. These findings suggest that the observed declines in periodontal health status between phases is not due to examiner bias. This unexplained decline may be the result of sampling variation. It is recommended that combined six-year survey results be presented whenever possible.

Reducing the burden of oral and pharyngeal cancers.

In the United States, oral and pharyngeal cancers continue to result in significant morbidity and mortality. Dental professionals play a pivotal role in all facets of controlling the burden of oral and pharyngeal cancer-from efforts to prevent its occurrence, to ensuring that oral cancers are detected at the earliest possible stage, to treating these cancers, and to ensuring maximum quality of life and function for oral and pharyngeal cancer survivors. Individually and by making linkages within the community and beyond, dentists can help patients modify their risk of these cancers and can take steps to screen for them, thereby potentially improving survival and function of those who develop oral cancer. Creative partnerships between community dentists and academic and other research centers will help move knowledge of the biological processes involved in carcinogenesis and innovations in treatment into clinical practice. Partnerships between dental and medical professionals may also help efforts to reduce the morbidity related to oral and pharyngeal cancers. Local, state and national multidisciplinary initiatives are emerging that focus more broadly on risk factor control or oral and pharyngeal cancer issues. These many forms of cooperative approaches offer excellent opportunities to make a significant impact on reducing the incidence of and in treating these debilitating and disfiguring malignancies.

Scientific progress in understanding oral and pharyngeal cancers.

Oral and pharyngeal cancers result from a complex interaction between genetic susceptibility and behavioral factors. Improved understanding of the underlying genetic events has led to insights about how oral and pharyngeal cancers develop and suggests promising new treatments. Tobacco and alcohol consumption are associated with most oral and pharyngeal cancers. Dental professionals' efforts to modify their patients' tobacco and alcohol use and to detect oral lesions at an early stage, together with scientific advances, will help reduce the impact of these cancers.

Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers.

BACKGROUND: The consumption of alcoholic beverages is a strong risk factor for cancers of the oral cavity and pharynx (oral cancers). Alcohol dehydrogenase type 3 (ADH3) metabolizes ethanol to acetaldehyde, a carcinogen. We evaluated whether individuals homozygous for the fast-metabolizing ADH3(1) allele (ADH3[1-1]) have a greater risk of developing oral cancer in the presence of alcoholic beverage consumption than those with the slow-metabolizing ADH3(2) allele (ADH3[1-2] and ADH3[2-2]). METHODS: As part of a population-based study of oral cancer conducted in Puerto Rico, the ADH3 genotypes of 137 patients with histologically confirmed oral cancer and of 146 control subjects (i.e., individuals with no history of oral cancer) were determined by molecular genetic analysis of oral epithelial cell samples. Risks were estimated by use of multiple logistic regression analyses. RESULTS: Compared with nondrinkers with the ADH3(1-1) genotype, consumers of at least 57 alcoholic drinks per week with the ADH3(1-1), ADH3(1-2), and ADH3(2-2) genotypes had 40.1-fold (95% confidence interval [CI] = 5.4-296.0), 7.0-fold (95% CI = 1.4-35.0), and 4.4-fold (95% CI = 0.6-33.0) increased risks of oral cancer, respectively; the risk associated with the ADH3(1-1) genotype, compared with the ADH3(1-2) and ADH3(2-2) genotypes combined, was 5.3 (95% CI = 1.0-28.8) among such drinkers. Considering all levels of alcohol consumption, the risk of oral cancer per additional alcoholic drink per week increased 3.6% (95% CI = 1.9%-5.4%) for subjects with the ADH3(1-1) genotype and 2.0% (95% CI = 0.9%-3.0%) for subjects with the ADH3(1-2) or ADH3(2-2) genotype (two-sided P = .04). CONCLUSIONS: The ADH3(1-1) genotype appears to substantially increase the risk of ethanol-related oral cancer, thus providing further evidence for the carcinogenicity of acetaldehyde.

Oral mucosal smokeless tobacco lesions among adolescents in the United States.

The presence of oral smokeless tobacco lesions among adolescents may be an early indicator of increased risk for oral cancers. Data from the 1986-1987 National Survey of Oral Health in US School Children were used to examine the cross-sectional relationship between the use of tobacco and alcohol and the presence of white or whitish oral soft-tissue lesions. The sample included 17,027 schoolchildren (aged 12 to 17 years) who provided information on the use of snuff, chewing tobacco, cigarettes, and alcohol and who received oral clinical examinations. Smokeless tobacco lesions were detected in 1.5% of students (projects to about 300,000 nationally), including 2.9% of males and 0.1% of females. These lesions were more prevalent among whites (2.0%) than among African-Americans (0.2%) or Hispanics (0.8%). Modeling with multivariate logistic regression revealed that, among white males, current snuff use was the strongest correlate of lesions [odds ratio (OR) = 18.4; 95% confidence interval (CI) = 8.5-39.8], followed by current chewing tobacco use [OR = 2.5; 95% CI = 1.3-5.0]. Lesions were strongly associated with duration, monthly frequency, and daily minutes of use of snuff and chewing tobacco. These data suggest that snuff may be a stronger risk factor than chewing tobacco for smokeless tobacco lesions, but the use of either of these forms of oral tobacco exhibits a dose-response relationship with the occurrence of lesions. We found little evidence that the use of alcohol or cigarettes may increase the risk of smokeless tobacco lesions. Preventing smokeless tobacco lesions and their possible malignant transformation may be best accomplished among adolescents by preventing the use of snuff and chewing tobacco.

Epidemiology of cancer and other systemic effects associated with the use of smokeless tobacco.

Persons who use chewing tobacco and snuff experience an increased risk of oral cancer. Because of the pharmacologic properties of nicotine and other constituents of smokeless tobacco, there is also concern that smokeless tobacco products may lead to cardiovascular diseases as well. The relatively few human population studies to date conflict with respect to whether smokeless tobacco use elevates cardiovascular risk factors or leads to cardiovascular disease or death from cardiovascular causes. Hemoglobin adducts to carcinogens present in smokeless tobacco products are measurable in the blood of smokeless tobacco users, indicating that smokeless-tobacco-related carcinogens circulate throughout the body. This prompts a concern that smokeless tobacco may increase risks of other cancers as well. The evidence to date from epidemiologic studies indicates no relationship between smokeless tobacco and bladder cancer, but there is suggestive evidence linking smokeless tobacco use to prostate cancer risk. Only single studies have been conducted of some cancers, and inconsistencies among studies of the same cancer site have been reported. Molecular epidemiologic studies may help identify markers of malignant transformation in smokeless tobacco users that may help in early intervention to prevent or ameliorate the consequences of oral cancer. Further studies are needed to determine more clearly the cardiovascular and non-oral cancer risks potentially associated with smokeless tobacco use.