Table 1.

Summary of studies to define human buccal cell changes associated with the smoking of tobacco

No.First author (year) (ref.)Primary aim (other aims) [confounders]Smoking history
Buccal cell
1Belowska (2004) (27)Smoking and buccal cells (larynx tumors) [air pollution]4900MicronucleusYesPatients with malignant tumors of the larynx showed a higher frequency of micronuclei in buccal cells of smokers and individuals exposed to airborne mutagenic substances.
2Wu (2004) (28)Smoking, buccal cells, and chewing of betel nut [age, alcohol, tea, diet, occupation, and vitamin supplements]56850MicronucleusYesHeavy smoking was positively associated with micronuclei frequency; areca quid chewing was negatively associated. A significant positive trend was shown for the relationship between micronuclei frequency and either daily cigarette consumption or cumulative smoking pack-years. All confounders studied were negative.
3Montero (2003) (33)Smoking and buccal cells (urban environment and pollution) [body mass and diet]10270MicronucleusExc-α, Exc-βStudied 11- to 16-year-old girls in urban environment for metabolic polymorphism. Study limitations: few smokers (n = 10), low smoking (thrice weekly; two cigarettes per occurrence). No increase in buccal cell micronuclei.
4Konopacka (2003) (34)Smoking and buccal cells [age and gender]50700MicronucleusYesAverage buccal cell micronuclei frequency (1.50 ± 0.47%) of smokers was significantly higher than nonsmokers (0.55 ± 0.32%). Higher frequency of micronuclei was observed for cells collected from female smokers (1.54 ± 0.42%) than male smokers (1.31 ± 0.56%). Age and gender did not influence micronuclei frequency of nonsmokers.
5Stich (1983) (56)Smoking and buccal cells (oral cancer) [alcohol]2002000MicronucleusNoAn elevated frequency of micronuclei of buccal cells from the cheek and tongue was observed only for subjects who smoked and drank alcohol. Neither smoking alone or drinking alone was associated with an elevated frequency of micronuclei.
6Suhas (2004) (31)Smoking and buccal cells (oral pathology) [bedi smoking]25250MicronucleusYesPeople of India who smoked bedi displayed higher micronuclei frequency of cells harvested from the buccal mucosa and palate (P ≤ 0.01) but not the tongue. The correlation between micronuclei and age was weak.
7Piyathilake (1995) (53)Smoking and buccal cells (vitamin deficiency) [age, gender, race, and diet]39600MicronucleusYesBuccal cell micronuclei were more frequent among cigarette smokers (mean = 20 pack-years) than nonsmokers. Micronuclei-positive cells occurred twice as often among Whites compared with Blacks. Age and gender were also important variables affecting micronuclei frequency. None of several dietary variables were associated with the presence of micronuclei in buccal cells.
8Benner (1994) (52)Smoking and buccal cells (clinical trials and oral leukoplakia) [alcohol]12019MicronucleusYesHigher buccal cell micronuclei frequency was recorded for buccal cells from lesions than normal-appearing mucosa. Observed a significant reduction (P < 0.01) in micronuclei frequency in buccal cells from both oral lesions and normal mucosa of subjects in an intervention trial evaluating α-tocopherol for chemoprevention of leukoplakia.
9Munoz (1987) (60)Smoking and buccal cells (clinical trials and esophageal cancer) [alcohol]20000MicronucleiExc-βDouble-blind intervention trial evaluating the effect of riboflavin, retinol, and zinc prevention trial for reducing precancerous lesions of the esophagus. No difference was observed for the frequency of micronuclei of buccal cells harvested before or after treatment. A significant reduction, however, was observed for esophageal cells in the treated vs placebo group. Study limitations: only two to three heavy smokers per smoking group.
10Li (1999) (43)Smoking and buccal cells (precancerous oral lesions and therapy)4600MicronucleiYesDouble-blind interventional trial conducted in patients with oral mucosa leukoplakia using a mixed-tea product. Increased micronuclei frequency was reported for leukoplakia group and was attributed to smoking. Significant reduction in micronuclei frequency and lesion size observed for the treated patients.
11Sarto (1987) (62)Smoking and buccal cells [alcohol and age]25250MicronucleiYesFrequency of buccal cell micronuclei that resulted from chromosomal breakage was double in smokers (0.95) compared with nonsmokers (0.41); this was statistically highly significant. In contrast, no correlation was recorded for micronuclei frequency. Other confounders were examined.
12Wrubel (1961) (63)Smoking and buccal cells (oral pathology)1100CytologyExc-α, Exc-γEvaluation of the keratinization patterns in oral mucosa of smokers did not find a decrease when subjects stopped smoking for period of a few weeks. Study limitations: only 11 smokers.
13Gordon (2002) (37)Smoking and buccal cells (infant death and sudden infant death syndrome) [passive smoke]NDNDNDBACYesBuccal cells from smokers bound significantly more bacteria than those from nonsmokers. Binding of Staphylococcus aureus correlated with tobacco smoke tar levels. Smoking is a major risk factor for sudden infant death syndrome.
14El Ahmer (1999) (42)Smoking, buccal cells, and bacterial pathogens (respiratory tract infections)16160BACYesAnalysis by flow cytometry showed an increased binding of all tested Gram-positive bacteria (3 species, 8 strains) and Gram-negative bacteria (4 species, 11 strains) to buccal cells from smokers compared with nonsmokers. Low amounts of cigarette smoke extract enhanced bacteria binding to the epithelial cells.
15Piatti 1997 (48)Smoking and buccal cells (oral infection)18180BACYesStudies of bacteria that colonize the mucosal surface, in a highly selective manner, showed an increase binding of pneumococcal adherence to buccal cells from smokers (46.92 ± 5.12 bacteria per cell) vs nonsmokers (29.85 ± 4.26 bacteria per cell).
16Niederman (1983) (55)Smoking and cells of the mouth, nose, and trachea (binding of bacteria)6100BACExc-αStudies using electron microscopy showed that cells from ciliated surfaces bound more bacteria than cells from squamous surfaces. Adherence of bacteria collected from different sites (i.e., trachea, nasal passage, and buccal mucosa) did not differ for smokers vs nonsmokers.
17Broberg (2005) (25)Smoking and buccal cells (bladder cancer)34122PCRYesTelomere length was significantly shorter in buccal cells from patients with cancer than in control subjects. When stratifying for smoking, a >6-fold risk was observed among current smokers.
18Koppikar (2005) (26)Smoking, buccal cells, and tumor cells (oral cancer and viruses) [chewing and alcohol]25280PCRExc-γPatients with oral cancer were studied for the presence of human papillomavirus in genomic DNA extracted from their tumor tissues and the corresponding adjacent normal mucosa. Human papillomavirus was detected in 32 of 102 patients.
19Moore (2004) (32)Smoking and buccal cells (polymorphism and bladder cancer)139760PCRYesBuccal cells were used to define the genetic polymorphism in detoxification enzymes for 102 bladder cancer cases and 109 healthy controls. Increased risk was associated with smoking was found for almost all genotypes studied.
20Elahi (2003) (35)Smoking and buccal cells (polymorphisms and orolaryngeal cancer)15674NoPCRYesDNA isolated from buccal cells was used to study the association of polymorphisms of glucuronidating activity against metabolites of the tobacco smoke carcinogen benzo[a]pyrene. Only six case participants were never smokers; thus, it was not possible to determine gene-smoking interactions.
21Spivack (2004) (30)Smoking and buccal cells (gene-environment) [gender and diet]1923PCRYesIn research to define gene-tobacco smoke interactions, buccal cells were proven useful for evaluating mRNA expression of nine genes encoding carcinogen- and oxidant-metabolism enzymes. Multivariate analyses showed that tobacco smoke exposure was associated with the level of expression of CYP1B1 and GSTP1.
22Elahi (2002) (36)Smoking and buccal cells (DNA repair and laryngeal cancer) [alcohol]NDNDNDPCRYesPCR analysis of buccal cell DNA was studied for 169 orolaryngeal cancer cases and 338 matched controls. No significant risk was observed for subjects with OGG1 genotype in never smokers; increased risk was observed for the cancer subjects (odds ratio, 4.8).
23Sweeney (2000) (41)Smoking and buccal cells (polymorphisms and oral cancer)517267NoPCRExc-αMost analyses were done using pathology tissue. Study limitations: of 490 patients studied, buccal cell tests were done for only 9 subjects.
24Morabia (2000) (40)Smoking and buccal cells (postmenopausal women and breast cancer)7157207PCRYesGene-smoking interaction was conducted using buccal cell DNA from 170 breast cancer cases and 170 age-matched population controls. Active smoking in postmenopausal women who were slow acetylators correlated with an increase risk of breast cancer (odds ratio, 2.5).
25Liu (1997) (47)Smoking and buccal cells [chewing of betel leaf]NDNDNDPCRYesStudy showed significant methylguanine-DNA methyltransferase activity of buccal cells and illustrated the potential inhibition of methylguanine-DNA methyltransferase by the habitual tobacco (bedi) smoking and betel quid chewing.
26Liede1998 (45)Smoking and buccal cells (leukoplakia) [vitamins]3430NDPCRNoStudy undertaken to define β-carotene concentrations in buccal cells in smokers who had received long-term β-carotene supplementation in a controlled trial. Observed reduced β-carotene levels in smokers. There was no correlation for smoking, β-carotene levels, and oral dysplasia.
27Phillips (2002) (39)Smoking and buccal cells (DNA adducts)NDNDNDDNA adductYesReview article on smoking-related DNA adducts and their association with cancer. Cited several other studies that showed higher levels of DNA adducts of buccal cells of smokers than of nonsmokers.
28Zhang (2002) (38)Smoking and buccal cells (malondialdehyde-DNA adducts)25250DNA adductYesMalondialdehyde-modified DNA adduct, used as a marker of human cancer risk, found increased levels of damage in smokers versus nonsmokers.
29Besarati (2000) (57)Smoking and buccal cells [polycyclic aromatic hydrocarbon (PAH)-DNA adducts]26220DNA adductYesIncreased in PAH-DNA adduct formation found in smokers than in nonsmokers. Adduct number was associated with tar content and number of cigarettes consumed per day.
30Romano (1999) (58)Smoking and buccal cells (PAH-DNA adducts)3364NoDNA adductYesImmunohistochemistry study of buccal cells showed a positive correlation between the numbers of PAH-DNA adducts and the number of cigarettes consumed per day.
31Hsu (1997) (46)Smoking and buccal cells (PAH-DNA and 4-aminobiphenyl adducts)20200DNA adductYesSmokers had 2- to 3-fold higher levels of PAH-DNA and 4-aminobiphenyl adducts compared with nonsmokers.
32Stich (1988) (54)Smoking and buccal cells (intervention trials)NDNDNDDNA adductYesReview of author's previous reports addressing DNA adducts, micronuclei, and leukoplakias as intermediate end points in intervention trials. Micronuclei meet many of the prerequisites of a good intermediate end point.
33Romano (1997) (59)Smoking and buccal cells (DNA adducts)12120DNA adductYesImmunohistochemistry showed an increased binding of stain to buccal cells of smokers. Stain intensity was related to number of DNA adducts.
34Stone (1995) (48)Smoking and buccal cells (DNA adducts in mucosa vs biopsy)8102DNA adductYesAuthors found that adduct levels were increased in smokers versus nonsmokers, with results being comparable between buccal mucosa and biopsy samples.
35Zhang (1995) (49)Smoking and buccal cells (PAH-DNA adducts)16160DNA adductYesObserved an increase in PAH-DNA adducts in smokers compared with nonsmokers. Variation among smokers was in the 3-fold range, illustrating individual differences in adduct formation.
36Oßwald (1996) (60)Smoking and buccal cells (chromosomal damage)1490CometNoEvaluated the yield and viability of buccal epithelial cells and leukocytes. Comet assay failed to detect a change in buccal cells of smokers.
37Rojas (1996) (51)Smoking and buccal cells (head/neck cancers)1090CometYesUsed single buccal cell gel electrophoresis test (Comet assay) for detection of DNA strand breaks. The extent of DNA damage was found to be significantly greater in smokers than nonsmokers.
38Barrera (1998) (44)Smoking and buccal cells (head/neck cancers)30300FISHYesFISH assay results documented higher chromosomal instability in smokers than in nonsmokers.
39Orellana-Bustos (2004) (29)Smoking and buccal cells (pathology and oral disease)3030NoAgNORYesWhen compared with nonsmokers, smokers with clinically normal buccal mucosa showed significant cytologic changes, including increased keratinization and higher nuclear (AgNOR) activity that is associated with acrocentric chromosomes.
  • * Assays for measuring buccal cell changes: BAC, adherence of bacteria to buccal cells; DNA adduct, binding of defined carcinogen to DNA; Comet assay, migration of buccal cell homogenate in an electric field; FISH, fluorescence in situ hybridization; AgNOR.

  • Statistically significant association identified between buccal cell changes and tobacco smoking: positive (yes) or negative (no) association.

  • Exc, report was excluded from analysis due to small number of subjects (Exc-α), low tobacco exposure (Exc-β), or no assessment presented by investigators (Exc-γ).