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Abstract

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case-control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose-response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26–5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07–5.22) and 2.83 (95% CI 2.18–3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42–4.64) and that of esophageal cancers was 3.41 (95% CI 1.46–7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2–4 years before the interview. © 2003 Wiley-Liss, Inc.

Oral, pharyngeal and esophageal cancer are 3 of the 5 most common cancer sites in males, as reported by the population-based cancer registries in Chennai and Trivandrum, and the age-standardized incidence rates of these neoplasms are among the highest in the world.1 Based on studies conducted in India and elsewhere, it has been established that oral, pharyngeal and esophageal cancers are causally related to the use of tobacco and alcohol.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Tobacco is most commonly smoked in India in the form of cigarettes and bidis. A bidi is a smoking stick 4–8 cm in length with 0.25–0.50g of coarse ground tobacco, made by rolling a dried piece of temburni leaf into a conical shape and securing it with a thread. Less common forms of smoking are cheroot, which is similar to the Western-type cigar, and chutta, which is a coarsely prepared cheroot, often smoked in reverse.18 Most studies from Southern India assessed the effect of cigarette and bidi smoking in the development of oral, pharyngeal and esophageal cancers, although the role of other smoking habits was not assessed.5, 6, 7, 8, 9, 10, 11, 12, 13, 14 A number of studies have shown an association between tobacco chewing and oral, pharyngeal and esophageal cancers.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Betal quid chewing without tobacco is common in South India, although the evidence for the role of chewing products without tobacco in the development of cancer is limited.4 Similarly, there is also no evidence for the role of various types of alcohol traditionally consumed in Southern India in the development of oral, pharyngeal and esophageal cancers. The types of alcohol consumed frequently include arrack (spirit containing 40–50% ethanol), country liquor (locally brewed spirit containing about 40% ethanol) and toddy (fermented sap from palm trees containing about 5% ethanol).2, 5

The objective of this study was to investigate the association with patterns of tobacco smoking, chewing and alcohol drinking in the development of oral, pharyngeal and esophageal cancers in Southern India and to assess interactions between the three habits.

MATERIAL AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

This study was conducted during 1993 and 1999 at the Cancer Institute in Chennai, Tamilnadu and the Regional Cancer Center in Trivandrum, Kerala. The cases were 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients. The sites were coded by the Ninth Revision of International Classification of Diseases (ICD-9).19 The oral cancer sites included were lip (ICD 140), tongue (ICD 141) and mouth (ICD 143–5). The pharyngeal cancer sites were oropharynx (ICD 146), hypopharynx (ICD 148) and pharynx unspecified (ICD 149). The ICD code for esophagus was 150. Male patients with non-tobacco-related cancers (ICD 152–154, 156, 158, 170, 171, 173, 175, 185, 187, 190) reported during the same study period from the same centers were selected as disease controls. All cases and cancer controls were histologically confirmed. In addition to 1,711 cancer controls from the two centers, 1,927 male healthy hospital visitors were also selected from Chennai as controls. All subjects were interviewed by trained social investigators. The subjects were questioned about demographic and socioeconomic parameters, clinical history, tobacco and alcohol habits, diet and occupational exposures.

Ever-smokers, chewers and drinkers were defined as those who smoked, chewed or consumed alcohol at least once a day for a minimum period of 6 months. Former smokers were defined as those who had stopped smoking 2 or more years before the interview. For the calculation of pack-years, the amount of tobacco in grams was estimated as 1 per cigarette, 0.5 per bidi and 2 per cigar, cheroot and chutta.3, 14 For the calculation of total lifetime consumption of ethanol, the percentage of ethanol was estimated as 0.40 for spirits (whisky, gin, rum, brandy, arrack and country liquor), 0.03 for beer and 0.05 for toddy.2, 5

Odds ratios (ORs) and 95% confidence intervals (CIs) for the sites under study were estimated according to smoking, chewing and alcohol habits using unconditional multiple logistic regression models.20 Interactions between the effects of the 3 habits were also assessed. All ORs were adjusted for age, center and level of education. ORs corresponding to 1 habit were obtained after adjusting for the other 2 habits, and the joint effects of 2 habits were obtained after adjusting for the third habit.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The two centers contributed 1,563 oral cancer cases, 636 pharyngeal cancer cases and 566 esophageal cancer cases and 3,638 controls. There were some disparities between the case and control groups regarding the distribution of age and level of education (Table I). Table II shows the risks of oral, pharyngeal and esophageal cancers associated with smoking, chewing and alcohol drinking habit. Current smokers showed about a 2-fold increased risk for oral cancer, about a 4-fold increased risk for pharyngeal cancer and around a 3-fold increased risk for esophageal cancer compared with never-smokers. Former smokers showed a significantly increased risk for esophageal cancer but not for oral and pharyngeal cancers. An increased risk for oral cancers of over 2-fold and a 60% increased risk for esophageal cancers were observed among chewers without tobacco, whereas among chewers with tobacco, the increase in risk was 5-fold (95% CI 4.26–5.97) for oral cancers and about 2-fold for pharyngeal (95% CI 1.43–2.33) and esophageal cancers (95% CI 1.62–2.63). A two-fold increased risk was observed among ever-drinkers for all 3 sites (Table II).

Table I. Distribution of Oral, Pharyngeal and Esophageal Cancer Cases and Controls by Center, Age and Level of Education
 OralPharynxEsophagusControls
No.%No.%No.%No.%
Center        
 Chennai65642.028344.526146.12,74775.5
 Trivandrum90758.035355.530553.889124.4
Age (yr)        
 25–34442.82264.0981.4169419.08
 35–4418411.77639.915810.2585423.47
 45–5446129.4918829.5613624.0388824.41
 55–6461539.3526341.3524843.8284223.14
 65–7421813.958413.2110618.733038.33
 ≥75412.62121.89101.77571.57
Level of education        
 None28718.3611317.776611.6644212.15
 Less than 5th year46229.5617227.0417530.9249313.55
 5th < high school58823.7727242.7724843.821,88676.23
 High school17511.206410.065710.0769319.05
 College/graduation513.26152.36203.531243.41
Table II. Odds Ratios of Oral, Pharyngeal and Esophageal Cancer for Smoking, Chewing and Alcohol Drinking
SiteControlCasesOR195% CIOR295% CI
  • 1

    Crude odds ratio (OR).

  • 2

    –OR adjusted for age, center, education level, two other habits.

  • 3

    –Reference category.

Oral cavity      
 Smoking      
  Never31,7994241.001.00
  Former4441851.761.45–2.160.830.65–1.06
  Current1,3959542.902.54–3.321.911.61–2.26
 Chewing      
  Never33,0797111.001.00
  Without tobacco181882.111.61–2.752.191.63–2.95
  With tobacco3747578.777.56–10.175.054.26–5.97
Alcohol drinking      
  Never32,9197801.001.00
  Ever7197834.083.58–4.631.981.68–2.33
Pharynx      
 Smoking      
  Never31,799871.001.00
  Former444572.651.87–3.771.230.84–1.79
  Current1,3954927.295.75–9.264.003.07–5.22
 Chewing      
  Never33,0794241.001.00
  Without tobacco181341.360.93–1.991.370.89–2.10
  With tobacco3741783.462.81–4.241.831.43–2.33
 Alcohol drinking      
  Never32,9192971.00  
  Ever7193394.633.89–5.522.071.67–2.56
Esophagus      
 Smoking      
  Never31,7991071.001.00
  Former444863.262.41–4.411.581.14–2.20
  Current1,3953734.503.59–5.642.832.18–3.66
 Chewing      
  Never33,0793711.001.00
  Without tobacco181331.511.03–2.231.601.05–2.45
  With tobacco3741603.552.87–4.402.061.62–2.63
 Alcohol drinking      
  Never32,9193041.001.00
  Ever7192623.502.91–4.211.701.36–2.13

Chewers with and without tobacco showed higher risks for cancer of the mouth [OR 6.95 (95% CI 5.72–8.46) and OR 2.60 (95% CI 1.82–3.73) for chewers with and without tobacco, respectively] than for cancer of the tongue, whereas smokers and alcohol drinkers showed higher risks for cancer of the oropharynx [OR 5.46 (95% CI 3.46–8.61) and OR 2.51 (95% CI 1.85–3.40) for current smokers and alcohol users, respectively] than for cancer of the hypopharynx (Table III).

Table III. Odds Ratios of Specific Oral and Pharyngeal Cancer Sites for Smoking, Chewing and Alcohol Drinking1
 Site (ICD code)
Tongue (140)Mouth (141–143)Oropharynx (146)Hypopharynx (148)
OR95% CIOR95% CIOR95% CIOR95% CI
  • 1

    Odds ratio (OR) adjusted for age, center, education level, two other habits.

  • 3

    –Reference category.

Smoking        
 Never31.001.001.001.00
 Former0.950.69–1.320.730.54–0.991.140.60–2.171.480.93–2.35
 Current1.921.52–2.431.791.45–2.225.463.46–8.613.732.66–5.24
Chewing        
 Never31.001.001.001.00
 Without tobacco1.711.13–2.592.601.82–3.731.450.77–2.741.340.78–2.30
 With tobacco2.742.18–3.436.955.72–8.461.741.25–2.431.981.46–2.68
Alcohol drinking        
 Never31.001.001.001.00
 Ever1.921.54–2.392.061.69–2.502.511.85–3.401.781.35–2.34

A significant dose-response relationship was observed between the duration of smoking and oral, pharyngeal and esophageal cancers up to the 40 years of smoking, after which no increase in the risk was observed (Table IV). Similarly, a significant dose-response relationship was also observed between the average daily amount of tobacco and all 3 sites of cancer up to 20 g of tobacco per day, after which no further increase was observed. All types of tobacco smokers showed a statistically significant increased risk for pharyngeal and esophageal cancers. For oral cancers, all types of smoking except cigarette smoking showed statistically significant increased risk. Cigar or cheroot smokers showed the highest increased risk for oral cancers, whereas bidi smokers showed the highest risk for pharyngeal and esophageal cancers. Decreased risk for all 3 sites were observed in former smokers compared with current smokers (Table IV).

Table IV. Odds Ratios for Oral, Pharyngeal and Esophageal Cancer for Duration and Amount of Smoking, Type of Tobacco Product and Time Since Quitting Smoking1
 ControlsOralPharynxEsophagus
CasesOR95% CICasesOR95% CICasesOR95% CI
  • 1

    Odds ratio (OR) adjusted for age, center, education level, alcohol consumption and chewing.

  • 2

    –Reference category: new smokers.

  • 3

    –Reference category: current smokers.

Never smokers1,7994241.00871.001071.00
Duration of smoking (yr)2          
 <207231881.210.95–1.52661.731.21–2.47591.611.12–2.31
 20–294742761.691.36–2.111222.852.06–3.931042.471.79–3.40
 30–393843821.911.53–2.381924.553.33–6.201482.902.13–3.94
 ≥402582931.601.25–2.061694.683.30–6.641482.882.06–4.02
 p for linear trend          
Average daily amount of tobacco (g)2          
 <91,1326311.411.18–1.692632.621.98–3.462322.121.62–2.78
 10–195343761.821.47–2.242224.173.10–5.621722.922.17–3.92
 ≥201621311.991.47–2.68633.762.53–5.60532.721.81–4.10
 p for linear trend          
Type of tobacco2          
 Cigarette only7892070.990.79–1.23851.791.29–2.50971.831.34–2.50
 Bidi only5484742.151.75–2.632484.683.50–6.271863.282.45–4.39
 Cigarette and bidi only3573661.491.18–1.881843.572.55–4.981552.721.95–3.79
 Chutta only83432.281.50–3.45173.221.85–5.7881.200.55–2.61
 Cigar/cheroot only18324.722.41–9.2574.281.63–11.2083.171.24–8.09
 Other combinations27161.560.75–3.2572.971.19–7.4241.390.45–4.23
Time since quitting smoking (yr)3          
 Current smokers1,3959541.004921.003731.00
 2–4148650.490.34–0.71240.420.23–0.67280.590.38–0.93
 5–997460.460.30–0.70130.300.16–0.55230.630.38–1.06
 10–1489250.260.15–0.4490.210.01–0.43150.450.24–0.81
 ≥1599490.510.34–0.76100.240.12–0.48190.530.31–0.90

Table V shows the risks of oral, pharyngeal and esophageal cancers associated with duration of chewing, average daily amount, cumulative chewing years and quitting. This analysis was not performed separately for chewers without and with tobacco because there were only 34 cases of pharyngeal cancers and 33 cases of esophageal cancers who used chewing without tobacco. A significant dose-response relationship was observed between the duration of chewing and all three sites of cancer up to 40 years of chewing, after which no further increase in the risk was observed for oral and esophageal cancers. A significant dose-response relationship was also observed between the average daily amount and all 3 sites of cancer and between the cumulative years of chewing and all 3 sites of cancer. The increase in risk for oral cancers was 12-fold (95% CI 8.93–15.96) and 13-fold (95% CI 8.49–20.89) for the highest categories of average daily amount and cumulative exposure to chewing, respectively (Table V). Quitting chewing only showed a decrease of risk for all 3 cancers after 10 years or more.

Table V. Odds Ratios of Oral, Pharyngeal and Esophageal Cancer for Duration, Level and Cumulative Chewing1
 ControlsOral cavityPharynxEsophagus
CasesOR95% CICasesOR95% CICasesOR95% CI
  • 1

    Odds ratio (OR) adjusted for age, center, education level, alcohol consumption and smoking.

  • 2

    –Reference category: new chewers.

  • 3

    –Reference category: current chewers.

Never chewing3,0797111.004241.003711.00
Duration of chewing (yr)2          
 0–192862503.112.51–3.86671.230.89–1.71711.781.30–2.45
 20–392094325.314.32–6.521011.971.46–2.67842.051.50–2.80
 ≥40641705.193.70–7.29442.601.60–4.20402.261.42–3.62
 p for linear trend          
Average daily amount (no. of quids)2          
 1–33432792.061.68–2.531011.210.91–1.61811.190.88–1.60
 4–51352736.024.70–7.72551.891.29–2.76512.181.48–3.19
 >580030011.948.93–15.96564.222.71–6.56636.074.03–9.14
 p for linear trend          
Cumulative exposure to chewing          
 <10001583543.782.95–4.841011.360.97–1.90690.940.66–1.34
 >10002621113.328.49–20.89311.971.05–3.68231.720.90–3.27
 p for linear trend          
Time since quitting chewing (yr)3          
 Current chewers4606401.001711.001601.00
 2–441931.150.75–1.77150.810.40–1.66120.510.24–1.09
 5–920591.600.92–2.81101.230.51–3.0180.900.36–2.26
 10–1419300.710.37–1.3560.450.15–1.3380.610.24–1.58
 ≥1519300.670.36–1.26100.570.24–1.3970.430.17–1.12

A significant dose-response relationship was observed for duration of drinking and average daily amount of ethanol consumption with oral, pharyngeal and esophageal cancers (Table VI). Among all types of alcohol analyzed, arrack drinkers showed the highest risk for oral, pharyngeal and esophageal cancers, the increase of risk being about 7-fold (95% CI 5.11–10.12), 4-fold (95% CI 2.49–6.16) and 4.5-fold (95% CI 2.90–7.29), respectively. The consumption of western-type spirits (gin, rum, whisky or brandy) did not show a significant increase of risk for any of the three sites (Table VI).

Table VI. Odds Ratios of Oral, Pharyngeal and Esophageal Cancer for Duration of Alcohol Drinking, Level and Type1
 ControlsOral cavityPharynxEsophagus
CasesOR95% CICasesOR95% CICasesOR95% CI
  • 1

    Odds ratios (OR) adjusted for age, center, education level, alcohol consumption and smoking. A total of 92 cases of oral cavity cancer, 30 cases of pharynx cancer, 25 cases of esophagus cancer and 143 controls consumed other combinations of beverages and were excluded form this analysis.

  • 2

    –Reference category: new chewers or drinkers.

Never drinkers2,9197801.002971.003041.00
Duration of chewing (years)2          
 <204282801.791.44–2.21891.361.01–1.83691.210.88–1.67
 20–291812452.061.62–2.621192.461.83–3.30821.691.23–2.34
 30–39851852.201.62–3.00972.952.06–4.21912.801.95–4.01
 ≥4025732.511.51–4.16343.061.72–5.45201.880.98–3.59
 p for linear trend          
Average daily amount of ethanol (ml)2          
 <203712131.230.98–1.54701.090.80–1.49701.130.83–1.55
 20–501782562.401.87–3.061062.341.71–3.21801.831.31–2.55
 >501673082.982.34–3.801623.602.70–4.821102.531.85–3.46
 p for linear trend          
Type of beverage          
 Arrack only661317.195.11–10.12393.912.49–6.16374.602.90–7.29
 Country liquor only1142331.731.30–2.321112.531.78–3.60681.460.99–2.14
 Spirits only2621011.040.78–1.38461.140.79–1.65390.970.65–1.44
 Cliq/arrac + spirits only41502.121.33–3.40232.421.37–4.26262.671.53–4.66
 Cliq/arrac + spirits + toddy only931761.801.32–2.46902.892.00–4.17672.001.35–2.95

Table VII shows the joint effects of smoking, drinking and chewing habits. It can be observed that both smoking and chewing with tobacco induced a significant increase of risk for oral, pharyngeal and esophageal cancer even for subjects who were never exposed to other habits. Chewing without tobacco and also drinking induced a significant increase of risk for oral and esophageal cancer for subjects never exposed to other habits. The role of drinking in the development of pharyngeal cancer for subjects never exposed to other habits could not be assessed because there were no pharyngeal cancer cases in this category. The joint effect of the three habits in the development of oral, pharyngeal and esophageal cancer appeared to be greater than additive, although less than multiplicative, inducing the highest increase of risk for pharyngeal and esophageal cancer. For oral cancer, a multiplicative interaction between drinking and chewing with tobacco was observed, inducing a 24-fold increase of risk.

Table VII. Odds Ratios of Oral, Pharyngeal and Esophageal Cancer for Combination of Smoking, Chewing and Alcohol Drinking1
SmokeChewingAlcoholControlsOral cavityPharynxEsophagus
CasesOR95% CICasesOR95% CICasesOR95% CI
  • 1

    Odds ratios (ORs) adjusted for age, center and education level. T+, with tobacco, T−, without tobacco.

  • b

    –Reference category.

NoNoNo1,4711221.00501.00451.00
NoYes-T−No83243.392.04–5.6651.600.61–4.1793.301.53–7.13
NoYes-T+No1271599.276.79–12.66253.732.20–6.31355.743.50–9.42
YesNoNo1,0842682.451.94–3.101753.542.54–4.941553.572.51–5.06
NoNoYes75162.561.42–4.64073.411.46–7.99
YesYes-T−No49254.802.79–8.27104.892.29–10.43104.822.23–10.44
YesYes-T+No1021618.536.13–11.89324.552.74–7.56487.224.47–11.64
NoYes-T−Yes156/4.361.55–12.3000
NoYes-T+Yes269524.2814.87–39.6574.281.72–10.62106.712.94–15.32
YesNoYes4492874.813.74–6.191998.415.94–11.901647.335.06–10.62
YesYes-T−Yes34338.104.68–14.021910.755.53–20.90149.124.35–19.12
YesYes-T+Yes11934216.3412.13–22.0011413.448.90–20.29678.655.50–13.62

Likelihood ratio test statistics for interactions among smoking, drinking and chewing habits were calculated by treating each of the habits as a dichotomous variable (Table VIII). Likelihood ratio tests were statistically significant (p < 0.05) for all combinations of the 3 habits except for the interaction between chewing and drinking for oral cavity and pharyngeal cancers, and between drinking and smoking for esophageal cancer. The tested models were adjusted for age, center, and education level and the third habit for 2-way interactions.

Table VIII. Likelihood Ratio Test for Interaction Models Between Drinking, Smoking and Chewing Habits, and Oral, Pharyngeal and Esophageal Cancer
 Oral cavityPharynxEsophagus
χ2pd.f.χ2pd.f.χ2pd.f.
Drinking and smoking5.140.0215.630.0210.240.621
Chewing and drinking2.120.1510.290.59112.660.001
Chewing and smoking30.180.0016.050.01117.970.001
Chewing and smoking and drinking32.480.00219.590.00225.030.002

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

In summary, the 3 habits analyzed were all significant risk factors for all 3 cancer sites. The study confirmed the previous findings that identified chewing as the strongest risk factor for oral cancer,5, 6, 7, 8, 16 in particular for chewing products containing tobacco. Chewing products without tobacco was also an independent risk factor for cancers of the oral cavity and esophagus, whereas the evidence concerning pharyngeal cancers was suggestive but not conclusive. For the latter cancer, smoking emerged as the strongest risk factor.

Chewing without tobacco induced a higher risk of esophageal cancer than chewing with tobacco.12, 13, 17 This may be explained by swallowing the liquid extract produced by chewing (chewers without tobacco) as opposed to spitting it out (chewers with tobacco).12 Another reason may be that the ORs were not adjusted for smoking and alcohol habits.12, 13, 17 The evidence concerning carcinogenicity of betel quid without tobacco was evaluated in 1985 as inadequate in the relevant IARC monograph on tobacco habits other than smoking.4 However, since that period, the potential mechanisms of carcinogenicity of betel quid without tobacco have been further elucidated. One of the major components of betel quid is the areca nut. In vitro evidence has shown that areca nut alkaloid arecoline can give rise to at least four N-nitrosamines. Two of these N-nitrosamines are carcinogens.21, 22, 23 Genotoxic and cytotoxic effects of areca nut extract and arecoline on various kinds of cells and cell growth-inhibiting effects on gingival keratinocytes, oral fibroblasts and oral mucosa cells have been demonstrated by a number of studies.24, 25, 26, 27, 28 Prostaglandins, which are inflammatory mediators, are considered to be important for tumor initiation, promotion and metastasis.29 Areca nut ingredients have also been suggested to be critical in the pathogenesis of oral cancer via their stimulatory effects on prostaglandins and cyclooxygenase-2.30 Roles for the p53 gene, certain protooncogenes and genetic polymorphisms in the carcinogenesis of oral cancer in betel quid chewers have also been proposed.31, 32, 33, 34

The higher risk for oral, pharyngeal and esophageal cancers among bidi smokers observed in the present study was consistent with results of previous studies,5, 6, 7, 10, 11, 12, 13, 14 except for the study of oral cancer in Bangalore,8 which was based on small number of bidi smokers. Reverse smoking of chutta has previously been associated with high rates of palatal cancer18 but not with significant risk for pharyngeal and esophageal cancers.35 In this study, information on whether chutta was smoked in reverse or in the ordinary manner was not available. Also, the role of chutta smoking in the development of palatal cancer could not be assessed because the fourth digit of the ICD code was not available. Nevertheless, in this study chutta smoking was a significant risk factor for cancers of the oral cavity and pharynx.

Quitting smoking conveyed a significant decrease in risk compared with current smokers for all 3 cancer sites, even for those who had stopped smoking 2–4 years before the interview, and was confirmed when we excluded chewers and drinkers from the analysis. No dose-response effect was observed with time since quitting smoking, and it could be hypothesized that smoking contributes to late-stage carcinogenesis in the development of oral, pharyngeal and esophageal cancer. Alcohol was an independent risk factor for all 3 cancer sites. Of the different types of alcohol analyzed, arrack exerted the strongest carcinogenic effect.

The evidence for interactions among the 3 habits from previous studies is inconsistent.5, 6, 7, 12, 13, 14, 15, 16, 17 This inconsistency might be attributed to the fact that previous studies did not control for alcohol consumption, which is an independent risk factor for the 3 cancer sites and therefore could be a strong confounder. Apart from not assessing alcohol consumption, the limitation of previous studies was a too small sample size for assessing interactions. In our study, the number of cases and controls was large enough to assess all 2-way and 3-way interactions. When assessing interaction between 2 habits, the third habit was controlled for. Only 2 previous studies from this region assessed the joint effects of combination of alcohol with other habits.14, 15 One study, restricted to oral cancer, identified a multiplicative interaction between chewing and drinking, as well as chewing and poor oral hygiene.14 The second study showed multiplicative interaction between alcohol consumption and smoking and alcohol consumption and chewing in the development of all 3 cancer sites, but the analysis was confined to only one age group.

Although our study has several limitations inherent to case-control studies, the advantages include a large sample size, a large heterogeneity of distribution of exposures, a detailed assessment of lifestyle habits and internal consistency of the results in both centers and for both groups of controls. From the public health point of view, the important finding of our study is a significant decrease of risk for oral, pharyngeal and esophageal cancers for subjects who had stopped smoking, which was already apparent after 2 years. Another important finding is the role of chewing without tobacco in the development of oral and esophageal cancers. In India this habit is not considered dangerous and is often indulged in by women and children. Finally, due to the well-established role of lifestyle factors in the development of oral, pharyngeal and esophageal cancers, they should be considered an important cause of avoidable morbidity and mortality in India, and their prevention should be an important target of public health initiatives.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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