- Email: [email protected]
ASSOCIATION BETWEEN ALCOHOL CONSUMPTION AND CANCER OF THE SIGMOID COLON: OBSERVATIONS FROM A JAPANESE COHORT STUDY
725
smokers. We are now testing this hypothesis with the assistance of the Meningococcal Reference Laboratory, Manchester. Since children from families of smokers are more likely to become smokers,22 their higher natural immunity would reduce their risk of getting meningococcal disease following acquisition of meningococci in adult life. We thank the DHSS for financial support. We are very grateful to Ron Warne for assistance with computer programming, to Paddy Farrington and Tony Hughes for statistical guidance, to Major L. Lodge, to the secretaries in the Department of Public Health Medicine, and to the people of Stonehouse who helped in the study.
Correspondence should be addressed to J. M. S., Gloucester Health Authority, Rikenel, Montpellier, Gloucester GLl 1LY.
Mueller JH. Meningococcus carrier rates and meningitis incidence. Bacteriol Rev 1950; 14: 115-60. 8. Olcen P, Kjellander J, Danielsson D, Lindequist BL. Epidemiology of Neisseria meningitidis: prevalence and symptoms from the upper respiratory tract in family members of patients with meningococcal disease. Scand J Infect Dis 1981; 13: 105-09. 9. Kristiansen B, Elverland H. Increased meningococcal carrier rate after tonsillectomy. Br Med J 1984: 288: 974. 10. Greenfield S, Sheehe PR, Feldman HA. Meningococcal carriage in a population of "normal" families. J Infect Dis 1971; 123: 67-73. 11. Pether JVS, Lightfoot NF, Scott RJD, Morgan J, Steel-Perkins AP, Sheard SC. Carriage of Neisseria metingitidis; investigations in a military establishment. 7.
Aycock WL,
Epidemiol Infect 1988; 101: 21-42. 12. Crofton J, Douglas A. Respiratory diseases. Oxford: Blackwell, 1981: 353. 13. Stephens DS, Whitney AM, Melly MA, Hoffman LH, Farley MM, Frasch CE. Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis. Infect Immun 1986; 51: 579-85. 14. Greenwood BM, Greenwood AM, Bradley AK, et al. Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West
Africa. J Infect 1987; 14: 167-84. Gilquin C, De Maeyer S, et al. Longitudinal study of asymptomatic meningococcal carriage in two Belgian populations of school children. J Infect 1983;
15. De Wals P,
6: 147-56.
REFERENCES
Haneberg B, Tonjum T, Rodahl K, Gedde-Dahl TW. Factors preceding the onset of meningococcal disease with special emphasis on passive smoking, stressful events, physical fitness and general symptoms of ill health. NIPH Ann 1983; 6: 169-74. 17. Stuart JM, Cartwright KAV, Dawson JA, Rickard J, Noah ND. Risk factors for meningococcal disease: a case control study in South West England. Community Med 1988; 10: 139-46. 18. Fraser PK, Bailey GK, Abbott JD, Gill JB, Walker DJC. The meningococcal
16. 1. Broome CV. The carrier state: Neisseria meningitidis. J
Antimicrob Chemother 1986; 18 (suppl A):25-34. 2. Cartwright KAV, Stuart JM, Jones DM, Noah ND. The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 1987; 99: 591-601. 3. Greenfield S, Feldman HA. Familial carriers and meningococcal meningitis. N Engl J Med 1967; 277: 497-502. 4.Blakebrough IS, Greenwood BM, Whittle HC, Bradley AK, Gilles HM. The epidemiology of infections due to Neisseria memngitidis and Neisseria lactamica in Northern Nigerian community. J Infect Dis 1982; 146: 626-37. 5. Kaiser AB, Hennekens CH, Saslaw MS, Hayes PS, Bennett JV. Seroepidemiology and chemoprophylaxis of disease due to sulphonamide-resistant Neisseria meningitids in a civilian population. J Infect Dis 1974; 130: 217-24. 6. Glover JA. Observations of the meningococcus carrier rate, and their application to the prevention of cerebrospinal fever. Special Report Series of the Medical Research Council (London) 1920; 50: 133-65.
ASSOCIATION BETWEEN ALCOHOL CONSUMPTION AND CANCER OF THE SIGMOID COLON: OBSERVATIONS FROM A JAPANESE COHORT STUDY TAKESHI HIRAYAMA Institute
of Preventive Oncology, Tokyo, Japan
17-year follow up of 265 118 Japanese adults aged 40 years and above revealed a close association between cancer of the sigmoid colon (n=91) and alcohol consumption: relative risk (RR) for drinkers versus non drinkers was 4·38 (90% CI 1·75-10·97) in men and 1·92(1·13-3·26) in women. In men, attributable risk was 74% and RRs in non, infrequent, occasional, and daily drinkers were 1·00, 2·03, 3·83, and 5·42, respectively. RRs of daily consumption versus non-consumption in men for cancers of mouth, pharynx, oesophagus, stomach, proximal colon, sigmoid colon, and rectum were 2·27,2·44, 2·29, 0·92, 0·98, 5·42, and 1·39, respectively. A combined effect of alcohol and smoking was evident for cancers of the upper digestive tract but almost absent for those of the lower
Summary
A
digestive tract. INTRODUCTION
THE number of deaths from
cancer
of the
sigmoid colon
has been increasing sharply in Japan. In 1987 there were 2709 such deaths, compared with 1665 in 1978-ratio of increase 1 65. The rise has been much steeper than that for other colon cancers and is almost as high as those for cancers of lung (1-71), liver (1-70), and pancreas (1-77). I have examined data from a large cohort study (1966-82) to identify major risk factors.
carrier-rate. Lancet 1973; i: 1235-37. 19. Wilson GS. Bacterial meningitis. In: Wilson GS, Miles AA, Parker MT, eds. Topley and Wilson’s Principles of bacteriology, virology and immunity. Vol 3. London: Edward Arnold, 1984: 369-81. 20. Cummins RO, Shaper AG, Walker M, Wale CJ. Smoking and drinking by middle-aged British men: effects of social class and town of residence. Br Med J 1981; 283: 1497-502. 21. Crowdy JP. Smoking in the army. J R Army Med Corps 1981; 127: 14-15. 22. Dobbs J, Marsh A. Smoking among secondary school children in 1984. London: HM Stationery Office, 1985: 53.
MATERIALS AND METHODS
From October to December, 1965, public health nurses conducted a questionnaire survey of all the residents aged 40 or older in 29 public health districts in six selected Japanese
prefectures. The prefectures (Miyagi, Aichi, Osaka, Hyogo, Okayama, and Kagoshima) were selected because they geographically represent the entire country and all but one (Kagoshima) had cancer registration systems. Respondents numbered 122 261 men and 142 857 women and the proportion of the respondents, as judged from the 1965 National Census population, was 94-8%. A one-page questionnaire was used in the survey to obtain information on smoking, drinking and dietary habits, occupation, marital status, and reproductive history. 98 % of the men and 95% of the women responded to questions about consumption of alcoholic beverages: 32 8% of these men were daily drinkers, 27-9% occasional drinkers (once or twice a week), 14-1% infrequent drinkers (once or twice a month), and 23-1% nondrinkers ; the corresponding percentages for women were 1-2, 5-5, 10-2, and 78-5.92% of the male drinkers answered questions about their usual drink-it was sake in 65%, beer in 22%, shochu (local hard liquor) in 10%, whisky in 2%, and other in 1%. At the beginning of each follow-up year, a migration survey was conducted, by reference to the local residence registration, and those who were found to have migrated from the residential public health districts during the previous year were excluded from the mortality
follow-up. During 17 years of follow-up (1966-82), 14 740 (8794 M, 5946 F) died of cancer; 574 died of cancer of the colon (256 M, 318 F) and 91 of these (43 M, 48F) were identified as having died of cancer of the sigmoid colon. RESULTS
Diet The age-standardised mortality ratio or relative risk (RR) of daily and occasional consumers versus infrequent and non consumers of selected foods was studied for cancer of the
726
rates
the
population
attributable risk of alcohol
drinking is
74%, from the formula of It — lo/liwhere 1t is the rate for total population and lo is the rate for non-consumers ([2-52-066]=252 x 100).
Type of alcoholic beverage.-The highest risk for cancer of sigmoid colon was observed in daily beer drinkers, RR versus non-drinkers 12-57 (3-62-43-66). However, the importance of daily drinking of other types of alcoholic beverages cannot be neglected—daily drinkers of sake had an RR of 4-56 (1-63-12-19) and of shochu 5-90 (2-00-17-42) (fig 1). Frequency-response relation.-There was a clear-cut frequency-response relation: the RRs for cancer of the sigmoid in non, infrequent, occasional, and daily alcohol consumers were 100, 2-03 (0-54-7-32), 3-83 (1-55-12-10), and 5-42 (2-24-13-99), respectively (fig 1). Comparison with known alcohol-related diseases.-The strength of the association with alcohol consumption was much higher for cancer of the sigmoid colon than that for known alcohol-related diseases. RRs in non, infrequent, occasional, and daily drinkers were 1 -00,0-69,0-85, and 1 -66 for liver cirrhosis,1-00, 0-67, 0-73, and 2-27 for cancer of the mouth, 1-00, 0-70, 0 88, and 2-44 for cancer of the pharynx, and 1-00, 0-87, 1 04, and 2-29 for cancer of the oesophagus. Alcohol plus cigarette smoking.---For known alcoholthe
Fig I-Age-standardised RR for cancer of sigmoid colon by frequency of alcohol consumption and type of drink (males). *p < 005; tp < 0-01, tp< 0001.
sigmoid colon and other parts of the colon. For proximal colon no significant association with any of the foods was observed: RRs (90% confidence interval) were 1 04 (0-831-32) for milk,1-04 (0-79-1-37) for meat,1.29 (0-74-2-26) for fish, 1-42 (0-62-324) for green-yellow vegetables, 096 (0-72-1-28) for rice/wheat, and 1-23 (0-68-2-33) for soybean paste soup. For cancer of the sigmoid colon, age-adjusted RRs of daily or occasional versus infrequent or never for consumption of milk and meat were 2-59 (1-52-4 42) and 1-79 (0-87-3,66), respectively, suggesting a possible riskraising effect of animal fats; no increase in risk was associated with fish, RR 0-76 (029-2°02). The RRs for consumption of green-yellow vegetables, rice/wheat, and soybean paste soup-036 (014-0-92), 0 44 (0-26-0-73), and 0 30 (0-150-58), respec-tively-suggested a possible risk lowering effect of dietary fibre. Cigarette Smoking No significant association was observed with the habit of cigarette smoking: the age-adjusted RRs for daily smokers were 1-21 (0-90-1-62) for proximal colon and 1-42 (0-722-79) for sigmoid colon. Alcohol Relative risk.-A striking association was observed between alcohol consumption and cancer of the sigmoid colon. The age-standardised mortality ratio or RR of daily and occasional consumers versus infrequent and non was 3-95 (1-98-7-86) for sigmoid colon, compared with a non-significant 1.07 (0-85-1-35) for proximal colon. The association between alcohol drinking and cancer of the sigmoid colon was seen in both sexes: RR of alcohol drinkers versus non-drinkers was 4-38 (1-7510-97) in men and 1-92 (1 13-3 26) in women. Attributable risk.-The age standardised mortality rates per 100 000 for cancer of the sigmoid colon in men are 2-52 consumers
for all groups and 0-66 for non alcohol drinkers. From these
related diseases there was a clear increase in nsk with cigarette smoking: RRs in those neither drinking nor smoking daily, in those drinking daily but not smoking daily, and in those both drinking and smoking daily were 1-00, 1-91, and 3-19 for cancer of mouth; 1-00, unassessable, and 4-54 for cancer of pharynx; and 1-00, 1-07, and 3-55 for cancer of the oesophagus. However, for cancer of the sigmoid colon no such tendency was observed and individuals who both smoked and drank even showed a slightly lower risk--RRs 1 00, 2-72, and 2-21. A similar pattern of association was seen with cancer of the rectumRRs 1 00, 1,92, and 1.75. Alcohol consumption and other cancers of digestive tract. -Alcohol drinking was closely associated with certain cancers of both upper and lower digestive tract, RRs of daily versus non-daily drinkers being 2-82 for cancer of the mouth, 2-87 for cancer of the pharynx, 2-28 for cancer of the oesophagus, 2-12 for cancer of the sigmoid colon, and 1-32 for cancer of the rectum; almost no association, however, was seen with cancer of the stomach ( 1 O 1 ), duodenum and small intestine (1-20), caecum (1-05), upper and transverse colon (0-95), or descending colon (1-0). A more impressive pattern was observed when RRs of daily drinkers were compared with those of non-drinkers-mouth 2-27, pharynx 2-44, oesophagus 2-29, stomach 0-92, proximal colon 0-98, sigmoid colon 5-42, and rectum 1-39 (fig 2). RR for cancer of sigmoid adjusted for cigarette smoking and diet.-The RR of daily versus non-daily alcohol consumption was adjusted, by the Mantel-Haenszel method, for smoking and consumption of green-yellow vegetables: it
Fig 2-Age-standardised RR for cancers of digestive tract by frequency of alcohol consumption (males).
727
2-138 (90% CI 1 316-3 471:=6 65,p<005), while RRs for daily smoking, daily consumption of meat, and daily consumption of green-yellow vegetables were 1’ 177 (0-6110-561 (0176-1782; X2=0’68, 2267; x’=0-17, p>005), p > 0.05), and 0.684 (0410-1 139, =1 50, p > 0-05) when other factors were adjusted. RR was essentially unchanged when alcohol consumption was examined by frequency of milk consumption: RR for daily and occasional versus infrequent and non drinkers was 3-61 (1-48-3-81) in daily and occasional milk drinkers, 3-45 (1-01-11-79) in infrequent and non milk drinkers, and 3-52 (1-73-7-31; x2=8.33, p<0-01) when frequency of milk consumption was adjusted. The association with milk consumption persisted when adjusted for frequency of alcohol drinking, the RR for daily and occasional versus infrequent and non consumption being 2-21 (1-16-4-21) in daily and occasional alcohol drinkers, 2-11 (0-50-8-87) in infrequent and non alcohol drinkers, and 220 (1-22-3-95; x2=4.86, p<0-05) when frequency of alcohol drinking was adjusted. Thus these two factors were associated almost independently with the disease. was
DISCUSSION
The close association between alcohol consumption and of the sigmoid colon was an unexpected fmding, and seemed to be specific to the sigmoid colon. It is also noteworthy that associations between dietary habits and cancer were similarly specific to the sigmoid--eg, the positive associations with milk and meat consumption and the negative associations with green-yellow vegetable and soybean paste soup consumption. The published work gives conflicting results on the relation of alcohol to colorectal cancer. Suggestive evidence for a possible association was obtained from correlation studies—eg, with colorectal cancer,’ with rectal cancersand with both colon and rectal cancer. Evidence of the association was also obtained from case-control studies--eg, in Liverpool for intestinal cancer;4 in New York for rectal cancer (beer);5,6 in Minnesota for rectal cancer (beer) and for colon cancer (spirits);7 in a patient interview as part of the third National Cancer Survey in USA for colon cancer, in men but not in women, and for rectal cancer in women but not in men;8 in Toronto, for rectal cancer (beer) but not for colon cancer;9 in Adelaide for colon and rectal cancer;10 and in Melbourne for rectal cancer (beer) but not for colon cancerY However, some case-control studies did not show any associations.7,12.13 The issue was also examined in cohort studies. Findings for alcoholics were mostly negative.14-18 Danish brewery workers had no excess of colorectal cancer19 whereas Irish brewery workers had twice the expected rate .20 Alcohol use was not significantly associated with colon cancer in the Framingham study.21 In Hawaiian Japanese there was a positive relation for rectal cancer but not for colon cancer after adjustment for age and smoking.22 A study in Japanese doctors showed no relation for colorectal cancer.23 In a cohort study conducted in California2’ the RR for colorectal cancer was 2-2 (90% CI 12-3-8) after multivariate adjustment. Essentially the same results were obtained when the cases of rectal cancer were omitted. None of these reports dealt specifically with cancer of the sigmoid colon. The mechanism of the close association between alcohol consumption and sigmoid cancer must be different from that of other known alcohol-related cancers (mouth, pharynx, and oesophagus) where alcohol is synergic cancer
with cigarette smoking. If cancer of the sigmoid colon is confirmed to be a purely alcohol-related disease what could be the mechanism? There may be a parallel with cancer of the rectum. It is noteworthy that in our current study the highest risk was observed in daily beer drinkers. Possible mechanisms are: a direct effect of alcohol on the motor system (eg, slowing down or causing irregularity of bowel movement) and on blood vessels (eg, congestion); effects of metabolites of alcohol (eg, acetaldehyde); effects of contaminants of alcoholic beverages such as mycotoxin, polycyclic hydrocarbons, N-nitrosamines, and asbestos fibres; induction of microsomal enzymes and activation of procarcinogens; effects of alcohol on hormonal balance and on the chemical composition of bile acids through liver damage by long-term heavy drinking; prevention of firstpass clearance by the liver of selected carcinogens;25.26 effects of alcohol on the intestinal flora; dietary habits peculiar to alcohol drinkers (eg, highly salted food and low fibre diet); and effects of various nutritional deficiencies characteristic of alcohol drinkers, some of which may be associated with
immunosuppression. Correspondence should be addressed to T. H., Institute of Preventive Oncology, HI Building, 1-2 Sadohara-cho, Shinjuku-ku, Tokyo, Japan. REFERENCES 1. Enstrom JE. Colorectal cancer and beer drinking. Br J Cancer 1977; 35: 674-83. 2. Kono S, Ikeda M. Correlation between cancer mortality and alcoholic beverage in Japan. Br J Cancer 1979; 40: 449-55. 3. Potter JD, McMichael AJ, Hartshome JM. Alcohol and beer consumption in relation Dis 1982; 35: to cancers of bowel and lung; an extended correlation analysis. Chron J 833-42. 4. Stocks P. Cancer incidence in North Wales and Liverpool region in relation to habits and environment. In: British Empire Cancer Campaign 35th Annual Report, part II (suppl), London: Bell, 1957. 5. Wynder EL, Shigematsu T. Environmental factors of cancer of the colon and rectum. Cancer 1967; 20: 1520-61. 6. Kabat CG, Howson CP, Wynder EL. Beer consumption and rectal cancer. Int J Epidemiol 1986; 15: 454-501. 7. Bjelke E. Epidemiologic studies of cancer of the stomach, colon, and rectum: with special emphasis on the role of diet. Thesis, University of Minnesota, 1973. 8. Williams RR, Horm JW. Association of cancer sites with tobacco and alcohol consumption and socio-economic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977; 58: 525-47. 9. Miller AB, Howe GR, Jain M, Craib KJP, Harrison L. Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer. Int J Cancer 1983; 32: 155-61. 10. Potter JD, McMichael AJ. Diet and cancer of the colon and rectum: a case-control study. J Natl Cancer Inst 1986; 76: 557-69. 11. Kune S, June GA, Watson LF. Case-control study on alcoholic beverages as etiological factor: The Melbourne Colorectal Cancer Study. Nutr Cancer 1987; 9: 43-51. 12. Higginson J. Etiological factors in gastrointestinal cancer in man. J Natl Cancer Inst
1966; 37: 527-45.
Tuyns AJ, Péquignot G, Gignoux M, Valla A. Cancers of the digestive tract, alcohol and tobacco. Int J Cancer 1982; 30: 9-11. 14. Sundby P. Alcoholism and mortality. Oslo: Universitetsforlaget, 1967. 15. Hakulinen T, Lehtimaki L, Lehtonen M, Teppo L. Cancer morbidity among two male cohorts with increased alcohol consumption in Finland. J Natl Cancer Inst
13.
1974; 52: 1711-14. 16. Adelstein A, White G. Alcoholism and mortality. Popul Trends 1976; 6: 7-13. 17. Monson RR, Lyon JL. Proportional mortality among alcoholics. Cancer 1975; 36: 1077-79. 18. Schmidt W, Popham RE. The role of drinking and smoking in mortality from cancer and other causes in male alcoholics. Cancer 1981; 47: 1031-41. 19. Jensen OM. Cancer morbidity and causes of death among Danish brewery workers. Int J Cancer 1979; 23: 454-63. 20. Dean G, MacLennan R, McLoughlin H, Shelley E. Causes of death of blue-collar workers at a Dublin brewery, 1954-73. Br J Cancer 1979; 40: 581-89. 21. Gordon T, Kannel WB. Drinking and mortality: the Framingham study. Am J Epidemiol 1984; 120: 97-107. 22. Pollack ES, Nomura AMY, Heibrun LK, Stemmermann GN, Green SB. Prospective study of alcohol consumption and cancer. N Engl J Med 1984; 310: 617-21. 23. Kono S, Ikeda M, Tokumode S, Nishizumi M, Kuratsune M. Alcohol and mortality: a cohort study of male Japanese physicians. Int J Epidemiol 1986; 15: 527-32. 24. Wu AH, Paganini-Hill A, Ross RK, Henderson BE. Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study. Br J Cancer 1987; 55: 687-94. 25. Anderson LM, Harrington GW, Pylypiw HM Jr, Hagiwara A, Magee PN. Tissue levels and biological effects of N-nitrosodimethylamine in mice during chronic low or high dose exposure with or without ethanol Drug Metab Disposition 1986; 14: 733-39. 26. IARC. Alcohol drinking. IARC Monogr Eval Carcinogenic Risks Hum 1988; 44: 120-21.
smokers. We are now testing this hypothesis with the assistance of the Meningococcal Reference Laboratory, Manchester. Since children from families of smokers are more likely to become smokers,22 their higher natural immunity would reduce their risk of getting meningococcal disease following acquisition of meningococci in adult life. We thank the DHSS for financial support. We are very grateful to Ron Warne for assistance with computer programming, to Paddy Farrington and Tony Hughes for statistical guidance, to Major L. Lodge, to the secretaries in the Department of Public Health Medicine, and to the people of Stonehouse who helped in the study.
Correspondence should be addressed to J. M. S., Gloucester Health Authority, Rikenel, Montpellier, Gloucester GLl 1LY.
Mueller JH. Meningococcus carrier rates and meningitis incidence. Bacteriol Rev 1950; 14: 115-60. 8. Olcen P, Kjellander J, Danielsson D, Lindequist BL. Epidemiology of Neisseria meningitidis: prevalence and symptoms from the upper respiratory tract in family members of patients with meningococcal disease. Scand J Infect Dis 1981; 13: 105-09. 9. Kristiansen B, Elverland H. Increased meningococcal carrier rate after tonsillectomy. Br Med J 1984: 288: 974. 10. Greenfield S, Sheehe PR, Feldman HA. Meningococcal carriage in a population of "normal" families. J Infect Dis 1971; 123: 67-73. 11. Pether JVS, Lightfoot NF, Scott RJD, Morgan J, Steel-Perkins AP, Sheard SC. Carriage of Neisseria metingitidis; investigations in a military establishment. 7.
Aycock WL,
Epidemiol Infect 1988; 101: 21-42. 12. Crofton J, Douglas A. Respiratory diseases. Oxford: Blackwell, 1981: 353. 13. Stephens DS, Whitney AM, Melly MA, Hoffman LH, Farley MM, Frasch CE. Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis. Infect Immun 1986; 51: 579-85. 14. Greenwood BM, Greenwood AM, Bradley AK, et al. Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West
Africa. J Infect 1987; 14: 167-84. Gilquin C, De Maeyer S, et al. Longitudinal study of asymptomatic meningococcal carriage in two Belgian populations of school children. J Infect 1983;
15. De Wals P,
6: 147-56.
REFERENCES
Haneberg B, Tonjum T, Rodahl K, Gedde-Dahl TW. Factors preceding the onset of meningococcal disease with special emphasis on passive smoking, stressful events, physical fitness and general symptoms of ill health. NIPH Ann 1983; 6: 169-74. 17. Stuart JM, Cartwright KAV, Dawson JA, Rickard J, Noah ND. Risk factors for meningococcal disease: a case control study in South West England. Community Med 1988; 10: 139-46. 18. Fraser PK, Bailey GK, Abbott JD, Gill JB, Walker DJC. The meningococcal
16. 1. Broome CV. The carrier state: Neisseria meningitidis. J
Antimicrob Chemother 1986; 18 (suppl A):25-34. 2. Cartwright KAV, Stuart JM, Jones DM, Noah ND. The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 1987; 99: 591-601. 3. Greenfield S, Feldman HA. Familial carriers and meningococcal meningitis. N Engl J Med 1967; 277: 497-502. 4.Blakebrough IS, Greenwood BM, Whittle HC, Bradley AK, Gilles HM. The epidemiology of infections due to Neisseria memngitidis and Neisseria lactamica in Northern Nigerian community. J Infect Dis 1982; 146: 626-37. 5. Kaiser AB, Hennekens CH, Saslaw MS, Hayes PS, Bennett JV. Seroepidemiology and chemoprophylaxis of disease due to sulphonamide-resistant Neisseria meningitids in a civilian population. J Infect Dis 1974; 130: 217-24. 6. Glover JA. Observations of the meningococcus carrier rate, and their application to the prevention of cerebrospinal fever. Special Report Series of the Medical Research Council (London) 1920; 50: 133-65.
ASSOCIATION BETWEEN ALCOHOL CONSUMPTION AND CANCER OF THE SIGMOID COLON: OBSERVATIONS FROM A JAPANESE COHORT STUDY TAKESHI HIRAYAMA Institute
of Preventive Oncology, Tokyo, Japan
17-year follow up of 265 118 Japanese adults aged 40 years and above revealed a close association between cancer of the sigmoid colon (n=91) and alcohol consumption: relative risk (RR) for drinkers versus non drinkers was 4·38 (90% CI 1·75-10·97) in men and 1·92(1·13-3·26) in women. In men, attributable risk was 74% and RRs in non, infrequent, occasional, and daily drinkers were 1·00, 2·03, 3·83, and 5·42, respectively. RRs of daily consumption versus non-consumption in men for cancers of mouth, pharynx, oesophagus, stomach, proximal colon, sigmoid colon, and rectum were 2·27,2·44, 2·29, 0·92, 0·98, 5·42, and 1·39, respectively. A combined effect of alcohol and smoking was evident for cancers of the upper digestive tract but almost absent for those of the lower
Summary
A
digestive tract. INTRODUCTION
THE number of deaths from
cancer
of the
sigmoid colon
has been increasing sharply in Japan. In 1987 there were 2709 such deaths, compared with 1665 in 1978-ratio of increase 1 65. The rise has been much steeper than that for other colon cancers and is almost as high as those for cancers of lung (1-71), liver (1-70), and pancreas (1-77). I have examined data from a large cohort study (1966-82) to identify major risk factors.
carrier-rate. Lancet 1973; i: 1235-37. 19. Wilson GS. Bacterial meningitis. In: Wilson GS, Miles AA, Parker MT, eds. Topley and Wilson’s Principles of bacteriology, virology and immunity. Vol 3. London: Edward Arnold, 1984: 369-81. 20. Cummins RO, Shaper AG, Walker M, Wale CJ. Smoking and drinking by middle-aged British men: effects of social class and town of residence. Br Med J 1981; 283: 1497-502. 21. Crowdy JP. Smoking in the army. J R Army Med Corps 1981; 127: 14-15. 22. Dobbs J, Marsh A. Smoking among secondary school children in 1984. London: HM Stationery Office, 1985: 53.
MATERIALS AND METHODS
From October to December, 1965, public health nurses conducted a questionnaire survey of all the residents aged 40 or older in 29 public health districts in six selected Japanese
prefectures. The prefectures (Miyagi, Aichi, Osaka, Hyogo, Okayama, and Kagoshima) were selected because they geographically represent the entire country and all but one (Kagoshima) had cancer registration systems. Respondents numbered 122 261 men and 142 857 women and the proportion of the respondents, as judged from the 1965 National Census population, was 94-8%. A one-page questionnaire was used in the survey to obtain information on smoking, drinking and dietary habits, occupation, marital status, and reproductive history. 98 % of the men and 95% of the women responded to questions about consumption of alcoholic beverages: 32 8% of these men were daily drinkers, 27-9% occasional drinkers (once or twice a week), 14-1% infrequent drinkers (once or twice a month), and 23-1% nondrinkers ; the corresponding percentages for women were 1-2, 5-5, 10-2, and 78-5.92% of the male drinkers answered questions about their usual drink-it was sake in 65%, beer in 22%, shochu (local hard liquor) in 10%, whisky in 2%, and other in 1%. At the beginning of each follow-up year, a migration survey was conducted, by reference to the local residence registration, and those who were found to have migrated from the residential public health districts during the previous year were excluded from the mortality
follow-up. During 17 years of follow-up (1966-82), 14 740 (8794 M, 5946 F) died of cancer; 574 died of cancer of the colon (256 M, 318 F) and 91 of these (43 M, 48F) were identified as having died of cancer of the sigmoid colon. RESULTS
Diet The age-standardised mortality ratio or relative risk (RR) of daily and occasional consumers versus infrequent and non consumers of selected foods was studied for cancer of the
726
rates
the
population
attributable risk of alcohol
drinking is
74%, from the formula of It — lo/liwhere 1t is the rate for total population and lo is the rate for non-consumers ([2-52-066]=252 x 100).
Type of alcoholic beverage.-The highest risk for cancer of sigmoid colon was observed in daily beer drinkers, RR versus non-drinkers 12-57 (3-62-43-66). However, the importance of daily drinking of other types of alcoholic beverages cannot be neglected—daily drinkers of sake had an RR of 4-56 (1-63-12-19) and of shochu 5-90 (2-00-17-42) (fig 1). Frequency-response relation.-There was a clear-cut frequency-response relation: the RRs for cancer of the sigmoid in non, infrequent, occasional, and daily alcohol consumers were 100, 2-03 (0-54-7-32), 3-83 (1-55-12-10), and 5-42 (2-24-13-99), respectively (fig 1). Comparison with known alcohol-related diseases.-The strength of the association with alcohol consumption was much higher for cancer of the sigmoid colon than that for known alcohol-related diseases. RRs in non, infrequent, occasional, and daily drinkers were 1 -00,0-69,0-85, and 1 -66 for liver cirrhosis,1-00, 0-67, 0-73, and 2-27 for cancer of the mouth, 1-00, 0-70, 0 88, and 2-44 for cancer of the pharynx, and 1-00, 0-87, 1 04, and 2-29 for cancer of the oesophagus. Alcohol plus cigarette smoking.---For known alcoholthe
Fig I-Age-standardised RR for cancer of sigmoid colon by frequency of alcohol consumption and type of drink (males). *p < 005; tp < 0-01, tp< 0001.
sigmoid colon and other parts of the colon. For proximal colon no significant association with any of the foods was observed: RRs (90% confidence interval) were 1 04 (0-831-32) for milk,1-04 (0-79-1-37) for meat,1.29 (0-74-2-26) for fish, 1-42 (0-62-324) for green-yellow vegetables, 096 (0-72-1-28) for rice/wheat, and 1-23 (0-68-2-33) for soybean paste soup. For cancer of the sigmoid colon, age-adjusted RRs of daily or occasional versus infrequent or never for consumption of milk and meat were 2-59 (1-52-4 42) and 1-79 (0-87-3,66), respectively, suggesting a possible riskraising effect of animal fats; no increase in risk was associated with fish, RR 0-76 (029-2°02). The RRs for consumption of green-yellow vegetables, rice/wheat, and soybean paste soup-036 (014-0-92), 0 44 (0-26-0-73), and 0 30 (0-150-58), respec-tively-suggested a possible risk lowering effect of dietary fibre. Cigarette Smoking No significant association was observed with the habit of cigarette smoking: the age-adjusted RRs for daily smokers were 1-21 (0-90-1-62) for proximal colon and 1-42 (0-722-79) for sigmoid colon. Alcohol Relative risk.-A striking association was observed between alcohol consumption and cancer of the sigmoid colon. The age-standardised mortality ratio or RR of daily and occasional consumers versus infrequent and non was 3-95 (1-98-7-86) for sigmoid colon, compared with a non-significant 1.07 (0-85-1-35) for proximal colon. The association between alcohol drinking and cancer of the sigmoid colon was seen in both sexes: RR of alcohol drinkers versus non-drinkers was 4-38 (1-7510-97) in men and 1-92 (1 13-3 26) in women. Attributable risk.-The age standardised mortality rates per 100 000 for cancer of the sigmoid colon in men are 2-52 consumers
for all groups and 0-66 for non alcohol drinkers. From these
related diseases there was a clear increase in nsk with cigarette smoking: RRs in those neither drinking nor smoking daily, in those drinking daily but not smoking daily, and in those both drinking and smoking daily were 1-00, 1-91, and 3-19 for cancer of mouth; 1-00, unassessable, and 4-54 for cancer of pharynx; and 1-00, 1-07, and 3-55 for cancer of the oesophagus. However, for cancer of the sigmoid colon no such tendency was observed and individuals who both smoked and drank even showed a slightly lower risk--RRs 1 00, 2-72, and 2-21. A similar pattern of association was seen with cancer of the rectumRRs 1 00, 1,92, and 1.75. Alcohol consumption and other cancers of digestive tract. -Alcohol drinking was closely associated with certain cancers of both upper and lower digestive tract, RRs of daily versus non-daily drinkers being 2-82 for cancer of the mouth, 2-87 for cancer of the pharynx, 2-28 for cancer of the oesophagus, 2-12 for cancer of the sigmoid colon, and 1-32 for cancer of the rectum; almost no association, however, was seen with cancer of the stomach ( 1 O 1 ), duodenum and small intestine (1-20), caecum (1-05), upper and transverse colon (0-95), or descending colon (1-0). A more impressive pattern was observed when RRs of daily drinkers were compared with those of non-drinkers-mouth 2-27, pharynx 2-44, oesophagus 2-29, stomach 0-92, proximal colon 0-98, sigmoid colon 5-42, and rectum 1-39 (fig 2). RR for cancer of sigmoid adjusted for cigarette smoking and diet.-The RR of daily versus non-daily alcohol consumption was adjusted, by the Mantel-Haenszel method, for smoking and consumption of green-yellow vegetables: it
Fig 2-Age-standardised RR for cancers of digestive tract by frequency of alcohol consumption (males).
727
2-138 (90% CI 1 316-3 471:=6 65,p<005), while RRs for daily smoking, daily consumption of meat, and daily consumption of green-yellow vegetables were 1’ 177 (0-6110-561 (0176-1782; X2=0’68, 2267; x’=0-17, p>005), p > 0.05), and 0.684 (0410-1 139, =1 50, p > 0-05) when other factors were adjusted. RR was essentially unchanged when alcohol consumption was examined by frequency of milk consumption: RR for daily and occasional versus infrequent and non drinkers was 3-61 (1-48-3-81) in daily and occasional milk drinkers, 3-45 (1-01-11-79) in infrequent and non milk drinkers, and 3-52 (1-73-7-31; x2=8.33, p<0-01) when frequency of milk consumption was adjusted. The association with milk consumption persisted when adjusted for frequency of alcohol drinking, the RR for daily and occasional versus infrequent and non consumption being 2-21 (1-16-4-21) in daily and occasional alcohol drinkers, 2-11 (0-50-8-87) in infrequent and non alcohol drinkers, and 220 (1-22-3-95; x2=4.86, p<0-05) when frequency of alcohol drinking was adjusted. Thus these two factors were associated almost independently with the disease. was
DISCUSSION
The close association between alcohol consumption and of the sigmoid colon was an unexpected fmding, and seemed to be specific to the sigmoid colon. It is also noteworthy that associations between dietary habits and cancer were similarly specific to the sigmoid--eg, the positive associations with milk and meat consumption and the negative associations with green-yellow vegetable and soybean paste soup consumption. The published work gives conflicting results on the relation of alcohol to colorectal cancer. Suggestive evidence for a possible association was obtained from correlation studies—eg, with colorectal cancer,’ with rectal cancersand with both colon and rectal cancer. Evidence of the association was also obtained from case-control studies--eg, in Liverpool for intestinal cancer;4 in New York for rectal cancer (beer);5,6 in Minnesota for rectal cancer (beer) and for colon cancer (spirits);7 in a patient interview as part of the third National Cancer Survey in USA for colon cancer, in men but not in women, and for rectal cancer in women but not in men;8 in Toronto, for rectal cancer (beer) but not for colon cancer;9 in Adelaide for colon and rectal cancer;10 and in Melbourne for rectal cancer (beer) but not for colon cancerY However, some case-control studies did not show any associations.7,12.13 The issue was also examined in cohort studies. Findings for alcoholics were mostly negative.14-18 Danish brewery workers had no excess of colorectal cancer19 whereas Irish brewery workers had twice the expected rate .20 Alcohol use was not significantly associated with colon cancer in the Framingham study.21 In Hawaiian Japanese there was a positive relation for rectal cancer but not for colon cancer after adjustment for age and smoking.22 A study in Japanese doctors showed no relation for colorectal cancer.23 In a cohort study conducted in California2’ the RR for colorectal cancer was 2-2 (90% CI 12-3-8) after multivariate adjustment. Essentially the same results were obtained when the cases of rectal cancer were omitted. None of these reports dealt specifically with cancer of the sigmoid colon. The mechanism of the close association between alcohol consumption and sigmoid cancer must be different from that of other known alcohol-related cancers (mouth, pharynx, and oesophagus) where alcohol is synergic cancer
with cigarette smoking. If cancer of the sigmoid colon is confirmed to be a purely alcohol-related disease what could be the mechanism? There may be a parallel with cancer of the rectum. It is noteworthy that in our current study the highest risk was observed in daily beer drinkers. Possible mechanisms are: a direct effect of alcohol on the motor system (eg, slowing down or causing irregularity of bowel movement) and on blood vessels (eg, congestion); effects of metabolites of alcohol (eg, acetaldehyde); effects of contaminants of alcoholic beverages such as mycotoxin, polycyclic hydrocarbons, N-nitrosamines, and asbestos fibres; induction of microsomal enzymes and activation of procarcinogens; effects of alcohol on hormonal balance and on the chemical composition of bile acids through liver damage by long-term heavy drinking; prevention of firstpass clearance by the liver of selected carcinogens;25.26 effects of alcohol on the intestinal flora; dietary habits peculiar to alcohol drinkers (eg, highly salted food and low fibre diet); and effects of various nutritional deficiencies characteristic of alcohol drinkers, some of which may be associated with
immunosuppression. Correspondence should be addressed to T. H., Institute of Preventive Oncology, HI Building, 1-2 Sadohara-cho, Shinjuku-ku, Tokyo, Japan. REFERENCES 1. Enstrom JE. Colorectal cancer and beer drinking. Br J Cancer 1977; 35: 674-83. 2. Kono S, Ikeda M. Correlation between cancer mortality and alcoholic beverage in Japan. Br J Cancer 1979; 40: 449-55. 3. Potter JD, McMichael AJ, Hartshome JM. Alcohol and beer consumption in relation Dis 1982; 35: to cancers of bowel and lung; an extended correlation analysis. Chron J 833-42. 4. Stocks P. Cancer incidence in North Wales and Liverpool region in relation to habits and environment. In: British Empire Cancer Campaign 35th Annual Report, part II (suppl), London: Bell, 1957. 5. Wynder EL, Shigematsu T. Environmental factors of cancer of the colon and rectum. Cancer 1967; 20: 1520-61. 6. Kabat CG, Howson CP, Wynder EL. Beer consumption and rectal cancer. Int J Epidemiol 1986; 15: 454-501. 7. Bjelke E. Epidemiologic studies of cancer of the stomach, colon, and rectum: with special emphasis on the role of diet. Thesis, University of Minnesota, 1973. 8. Williams RR, Horm JW. Association of cancer sites with tobacco and alcohol consumption and socio-economic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst 1977; 58: 525-47. 9. Miller AB, Howe GR, Jain M, Craib KJP, Harrison L. Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer. Int J Cancer 1983; 32: 155-61. 10. Potter JD, McMichael AJ. Diet and cancer of the colon and rectum: a case-control study. J Natl Cancer Inst 1986; 76: 557-69. 11. Kune S, June GA, Watson LF. Case-control study on alcoholic beverages as etiological factor: The Melbourne Colorectal Cancer Study. Nutr Cancer 1987; 9: 43-51. 12. Higginson J. Etiological factors in gastrointestinal cancer in man. J Natl Cancer Inst
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