Plant Foods And Cancer RiskScience And Tradition

John D. Potter

and fruitS,5. It presents, in abbrevi­ated form, the available data on thequestion of whether the consumptionof vegetables and fruit is associatedwith a lower risk of cancer.

COHORT STUDIES

Particular vegetables and fruitshave long been believed to be usefulin the prevention and cure of dis­ease. Western medicine, until quiterecently, largely involved the prescrip­tion of specific plants and foods. Inancient Egypt, then later in Greeceand Rome, a wide variety of useswere found for many different plantsand extracts1• Garlic was considereda holy plant in Egypt. Cruciferousvegetables were cultivated primarilyfor medicinal purposes and were usedtherapeutically against several acuteand chronic disorders2• Celery, cu­cumber, endive, and a variety of herbsand vegetable juices had standarduses. Peas were used in a conditionthat may have been angina pectoris.

The Romans believed that len­

tils were a cure, for diarrhoea andconducive to an even temper (it is notclear whether these are related). Sev­eral fruits also were used therapeuti­cally: the citron (similar to the lemon)was believed to act as an antidote forpoisons; raisins and grapes were in­corporated into oral preparations,enemas, inhalations and topical ap­plications3.

The medical traditions of Indiaand China, particularly', have retainedand extended much of this therapeu­tic knowledge. Today, in the devel­oped world once again, there aremany interesting properties ascribedto edible plants, herbs, spices andfoods. Until relatively recently, how­ever, both ancient and modern thera­pies and preventive strategies were

based on many generations of clini­cal experience and not on evidencederived from epidemiological and ex­perimental studies.

DIET AND CANCER

In 1981, Doll and Peto produceda wide estimate of 10 to 70 per cent ofall cancer as being attributable todiet4• This conclusion was based onstudies showing increased risk inassociation with certain foods - par­ticularly foods of animal origin. Overthe past decade, however, many studieshave examined the effect of plantfood consumption on health and dis­ease. High consumption of vegetablesand fruit is protective against can­cers at many sites; this conclusionappears to be better supported byliterature than almost all other dietaryhypotheses.

There are many biologically plau­sible reasons why consumption ofvegetables and fruit might deter theoccurrence of cancer. These includethe presence of potentially anti­carcinogenic substances such as caro­tenoids, vitamin C, vitamin E, sele­nium, dietary fibre, dithiolthiones,isothiocyanates, indoles, phenols,protease inhibitors, allium compounds,plant sterols, limonene and others.However, the crucial issue is the com­plexity and variety of the mixtures,not the specific dose of one or twocompounds.

This paper presents an updateof our earlier review of the role ofplant foods - particularly vegetables

At least 21 cohort studies? haveexamined the relationship betweenvegetable and fruit consumption anddifferent types of cancer. Of these,19 found an inverse association for atleast one category of vegetable and/or fruit, and in 12 studies statisticallysignificant reductions in risk were re­ported. Of these studies, four reportedon all cancer sites; four on lung can­cer; three each on colorectal and stom­ach cancers; two each on pancre­atic, bladder and breast cancers; andone on prostate cancer.

It is lung cancer for which thecohort study evidence is the mostconsistent; inverse associations forvegetable and/or fruit consumptionhave been shown in populations ofNorwegian men, postmenopausal USwomen, Seventh Day Adventists, andmembers of a retirement communityin California. The association between

CONTENTS

•Plant Foods And Cancer Risk

- Science And Tradition

1

- John D. Potter

-

•Nutrition News 5

•Food Safety Evaluation -

National and InternationalPerspectives

6- Ramesh V. Bhatt and Pulkit Mathur•

Foundation News 8

colon cancer and vegetable consump­tion is not as consistent in the cohortstudies as in the case-control studiesreviewed below.

CASE-CONTROL STUDIES

Most of the evidence for an in­verse association with vegetable andfruit consumption comes from case­control studies. As early as 1933,such a study by Stocks and Karns inBritain suggested such an associa­tion between intake of certain veg­etables against cancer at all sites.Four hundred and sixty-two cancerpatients and 435 patients without can­cer, each of whom provided a diethistory, were compared.

The most common cancers werethose of the breast, the colon andrectum, the uterus and the tongue.Cases reported lower consumptionof carrots, turnips, cauliflower, cab­bage, onions, watercress and beetrootthan controls. Intake of these veg­etables combined was statistically sig­nificantly lower in the cases than inthe controls. Although the methodsemployed in this study were crude bymodern standards, it is striking tonote that this apparently protectiveeffect of vegetable consumption andof milk, along with the risk-enhancingeffects of pipe smoking and beerdrinking were the major findings ofthis study.

Another study, in the same yearin India, although less rigorous indesign, again found that vegetableconsumption was higher in those whodid not develop oral cancer comparedwith those who did9•

Since that time, nearly 200 morecase-control studies worldwide haveexamined the relationship betweenvegetable and fruit consumption andcancer risk. Stomach cancer has beenthe most studied, followed by can­cers of the colon, oesophagus, lung,oral cavity and pharynx, rectum andbreast; more than 10 studies havefocussed on each of these sites. Sta­tistically significant inverse associa­tions have been reported for one ormore vegetable and/or fruit catego­ries in more than 70 per cent of thestudies for cancers of the followingsites: stomach, oesophagus, lung,oral cavity and pharynx, endometrium,pancreas, colon and skin. Prost~tecancer is the only cancer for whichthe majority of studies have not re-

ported at least one statistically sig­nificant inverse association; and in­deed, for prostate cancer, no studyshows an inverse association. Someof these sites will now be reviewed inmore detail.

STOMACH CANCER

Thirty-one case-control studiesdealing with the relationship betweenvegetable and fruit consumption andstomach cancer have been reported.Twenty-eight of these studies foundan inverse association between can­cer and consumption of one or morevegetable and/or fruit.

The most consistent and abun­dant findings appear to be for theconsumption of fruit, raw vegetables(including lettuce) and allium vege­tables. Contrary to the pattern of in­verse associations between intakesof the above vegetables and freshfruits and stomach cancer, severalstudies suggested that consumptionof potatoes and canned fruit werepositively associated with risk.

Potential confounders of the re­lationship between stomach cancerand vegetable and fruit consumptioninclude socioeconomic status. Lower

socioeconomic status (as measuredby education level, occupation, and/or income) was found to correlatewith stomach cancer risk in many ofthe studies. In addition, the study byCorrea et a/10 was conducted in Loui­siana where stomach cancer ratesare much higher among blacks, whoare generally poor, as compared towhites in the area. Diet is likely to becorrelated with socioeconomic sta­tus and the consumption of fresh veg­etables and fruits, which tend to berelatively expensive, may be muchlower among the lower socioeconomicsections of a population. Nonethe­less, several of the odds ratios were

adjusted for the confounding eff~~tsof occupation, education, ethnlcltyand/or income as surrogates for so­cioeconomic status. These studiesstill noted a statistically significantinverse association between vegetableand fruit consumption and stomachcancer.

Consumption of pickled, fer­mented, salted and/or smoked foods,consumption of alcohol, consump­tion of large amounts of carbohy­drate (as potatoes or rice), infrequentmeals, non-ownership of a refrigera­tor, poor dentition, residence in a

2

rural vs urban area (which may betied to socioeconomic status), his­tory of chronic gastritis, blood type 0and smoking are other risk factors forstomach cancer elucidated by someof the studies reviewed here. Smok­ing is not as strong a risk factor forcancer of the stomach as for cancersofthe respiratory and upper gastrointes­tinal tracts.

COLON CANCER

Fifteen of the 21 case-controlstudies dealing with colon cancerfounda statistically significant inverse rela­tionship between cancer and at leastone index of vegetable and fruit con­sumption. Among specific categoriesof vegetables, the results for crucifer­ous vegetables were the most strik­ing in that most of the studies pre­senting findings for cruciferous vege­tables found higher intake to be as­sociated with lower risk.

Most of the studies showing nosignificant association or only posi­tive associations with vegetable andfruit consumption were among theearliest conducted, which may be areflection of more crude dietary meth­odology or perhaps less attention paidto detail in gathering fruit and veg­etable data (hypotheses regardingthese foods were not obvious at thetime these earlier studies were con­ducted).

OESOPHAGEAL CANCER

Fourteen case-control studies ofoesophageal cancer have examinedthe associations with vegetable andfruit consumption. Twelve found astatistically significant inverse rela­tionship between intake of one ormore vegetables and/or fruits andoesophageal cancer.

Consumption of vegetables, spe­cifically, was found to be invers~lyassociated in almost all of the studiesthat reported on this exposure and inmost cases, this was statistically sig­nificant. The association with pota­toes appears to be the most inconsis­tent. Consumption of fruit in general.was inversely associated with oeso­phageal cancer.

Consumption of red chilli pow­der was also found to be a risk fac­tor11• Although not a vegetable perse, such a risk may also apply towhole red chillies themselves. Alter­natively, the risk may be derived from

some part of the drying process oruse of red chilli powder may be amarker for use of some other spicethat is the actual agent.

Smoking and heavy alcohol con­sumption are well established as therisk factors that account for the ma­jority of oesophageal cancers in theindustrialised countries. These hab­its are associated with less healthfuleating patterns and poor nutritionalstatus. Thus, an obvious question iswhether the inverse associations foundwith vegetable and fruit consumptionin most of these case-control studiesare confounded by alcohol intake andsmoking. In fact, several of the stud­ies reviewed here supply evidencethat vegetable and fruit consumptionhas an independent effect with manyof the odds ratios being adjusted forsmoking or alcohol consumption.Strong consistency is observed acrossstudies: adjustment for smoking andheavy drinking does not reduce risksassociated with diet.

Some areas of the world, suchas parts of Iran, South Africa andChina, experience very high rates ofoesophageal cancer that are not nec­essarily attributable to smoking andalcohol consumption. In further sup­port of an independent effect of veg­etable and fruit consumption, inverseassociations were found12 betweenintake of many vegetables and fruitsand oesophageal cancers in Iran al­though the study in Un Xian, China,was essentially null. In these areas,identified risk factors include low socio­economic status, consumption of opiumand of known carcinogens in food,perhaps consumption of extremelyhot beverages and diets high in wheatand corn.

LUNG CANCER

Thirteen case-control studies oflung cancer have examined the ef­fects of vegetable and fruit consump­tion. Eleven found lower risk associ­ated with one or more vegetablesand/or fruits. Many of the studies foundconsumption of carrots (or dark yel­low-orange vegetables) to be asso­ciated with lower risk and somewhatfewer reported a similar result for leafygreen vegetables (also described askale, dark green vegetables or spin­ach). Carrots and greens are two ofthe most concentrated dietary sourcesof a variety of carotenoids.

In these studies, the benefit con-

ferred by high intake of vegetableswas often more evident in smokersthan nonsmokers but not all studiesexamined associations within thesmoking strata. One explanation forthe trend for stronger associations insmokers might be that the majority ofcases in most studies of lung cancerare smokers and there may not havebeen enough power to detect trueassociations in nonsmokers. Anotherpossibility is that the benefit conferredby vegetable consumption is a late­stage event that occurs after initia­tion by substances in cigarette smoke.Interestingly, a study of only non­smoking female patients in Hong Kong(64 per cent of female lung cancerpatients in Hong Kong have neversmoked), also found inverse asso­ciations for intakes of vegetables13.

ORAL AND PHARYNGEALCANCER

Thirteen case-control studies ofvegetable and fruit consumption andoral and pharyngeal cancer have beenreported. Ten of these studies re­ported an inverse association betweenoral and pharyngeal cancer and in­take of one or more vegetables and/or fruits.

Consumption of fruit appearedto be especially consistent, with anapproximate doubling of risk for con­sumers of the least vs the most amountsof fruit. No clear pattern emerged forspecific vegetables with the possibleexception of green vegetables whichwere associated with reduced risk infive of six studies.

As with oesophageal and laryn­geal cancer, the predominant risk fac­tors for oral and pharyngeal cancerare tobacco and alcohol. In most ar­eas of the world, smoking, chewing(including betel chewing) and drink­ing are estimated to account for 75per cent or more of the cancers ofthese sites. Each of the studies re­viewed here found these to be themajor risk factors. Poor dentition wasalso found to be a risk factor in a fewstudies. Because, as noted before,tobacco and alcohol habits may cor­relate inversely with food intake andthe nutritional quality of the diet, thepotential for a confounding effect ofthese habits on the relationship be­tween vegetable and fruit consump­tion and oral and pharyngeal canceris great. Nonetheless, there is ampleevidence of an independent inverse

association with vegetable and fruitconsumption.

BREAST CANCER

Thirteen case-control studies ofbreast cancer in 11 different coun­tries have examined the potential pro­tective effect of vegetable and fruitconsumption. Of these, nine found asignificant reduction of risk in asso­ciation with at least one vegetable orfru it catego ry.

Most of the breast cancer stud­ies focussed on fat intake as well asvegetable intake in order to shed lighton the controversial hypothesis con­cerning a role for a high-fat diet in theetiology of breast cancer. An inter­esting difference between the stud­ies that found associations betweenvegetable and fruit consumption andbreast cancer and those that did not,is that odds ratios were adjusted forpotential confounders in the studieswhich found a relationship. Theoreti­cally, high vegetable and fruit con­sumption may be associated posi­tively with risk factors for breast can­cer such as upper social class, bodyweight, and later age at first birth.Such correlations might obscure anyinverse association between vegetableand fruit consumption and breast cancerin the absence of adjustment.

Overall, the associations appearto be weaker than those seen forrespiratory and digestive cancers. Itmay be that the potential anti­carcinogenic actions of vegetablesand fruits are less applicable to breastcancer than non-hormone related epi­thelial cancers. For instance, mostlung and upper aerodigestive can­cers are strongly associated withsmoking, which provides a direct ex­posure to initiating agents, whereasfor breast cancer, the known risk ex­posures are mainly related to expo­sure to unopposed estrogen, whichmay have more of a promotional ef­fect. If the effect of potential anti­carcinogenic agents in vegetables andfruit is to block initiating events thenthese agents may be more effectivein preventing, say, lung than breastcancer. Nonetheless, an effect of in­doles, which are found in cruciferousvegetables, on estrogen metabolismhas been demonstrated and maybe relevant to the etiology of breastcancer.

Thus, the majority of the studiesshow no more than a halving of risk

with high consumption of vegetablesand fruit. It is commonly the case thatdietary risk or protective factors arenot shown to be as strong as otherrisk factors in epidemiological stud­ies. This may be in part due to attenu­ation of odds ratios due to the inabil­ity of dietary assessment methods toclassify diets of individuals with greatprecision. It may also be due in partto the narrow range of levels of expo­sure to dietary factors within mostpopulations.

Therefore, odds ratios consis­tently suggesting a doubling or halv­ing of risk pertinent to dietary expo­sures may in fact be signaling a strongerrelationship. Even if the risk of can­cer were only doubled by low veg­etable and fruit consumption, the im­portance would remain because theattributable risk would be high due towidespread exposure to low vegetableand fruit consumption and becausediet is a relatively modifiable entityand thus a potential target for change.

MECHANISMS

There are many biologically plau­sible reasons why consumption ofvegetables and fruit might reduce thelikelihood of cancer. These includethe presence of potentially anti­carcinogenic substances such ascarotenoids, ascorbate, tocopherols,selenium, dietary fibre, dithiolthiones,isothiocyanates, indoles, phenols,protease inhibitors, allium compounds,plant sterols, limonene and otherswhich are increasingly being called,collectively, phytochemicals or bio­active compounds - chemicals ofplant origin that playa crucial role inmammalian metabolism6.

When the body is first exposedto specific carcinogens, many arenot in thEilir active form; the stepsbetween exposure to the pro-carcino­gen and the conversion of a normalcell into a cancer-prone cell (trans­formation) can be considered as fol­lows: the pro-carcinogen is activatedto the ultimate carcinogen form byP450 enzymes. (It is worth keeping inmind that the body is not trying tomake carcinogens - it is trying tosolubilise insoluble foreign compoundsand therefore enable excretion in theurine.) However, this is complicatedby the fact that the same enzyme canoften make one compound less car­cinogenic and another more carcino­genic; either of the forms of the car-

cinogen - pro-carcinogen or ultimatecarcinogen - may be converted byPhase II enzymes into a form that isrelatively inert and even more easilyexcreted.

These are typified by glutathioneS-transferase; if not excreted, the car­cinogen can pass through the cellmembrane and the nuclear membrane;it can then interact with the DNA­forming adducts and/or produce mu­tations; DNA synthesis and replica­tion (or DNA repair) subsequentlyoccurs. Repair has varying degreesof fidelity; if the DNA is not repairedaccurately, cell replication - producingdaughter cells with copies of themutated DNA - occurs. These cellsthen synthesise an abnormal proteinor fail, altogether, to synthesise aprotein crucial to the normal functionof the cell or even crucial to control­ling cell replication itself (this is al­most certainly what happens when atumour suppressor gene [for example,P53] mutates or is deleted).

This sequence of stages bringsa cell a step closer to becoming acancer cell (alternatively, even withabnormal DNA, the cell may cease toreplicate and then undergo differen­tiation or apoptosis). DNA damageprobably has to occur several timesbefore a cell becomes completely freeof growth restraint and a fully cancer­ous one. Finally, the abnormal cellsobtain a growth advantage over thenormal cells and steadily increase innumbers (promotion) - often becomingmore malignant and able to spread(progression). These are steps thatthemselves involve further changesin the cellular DNA.

At almost everyone of the abovestages, known phytochemicals/bio­active compounds can alter the like­lihood of carcinogenesis, occasion­ally in a way that enhances risk, butusually in a favourable direction. Forexample, such substances as gluco­sinolates and indoles, isothiocyanatesand thiocyanates, phenols andcoumarins can induce a multiplicityof solubilising and (usually) inacti­vating enzymes; ascorbate and phenolsblock the formation of carcinogenssuch as nitrosamines; flavonoids andcarotenoids can act as antioxidants,essentially disabling carcinogenicpotential; lipid-soluble compounds suchas carotenoids and sterols may altermembrane structure or integrity; somesulphur-containing compounds can

4

suppress DNA and protein synthesiscarotenoids suppress DNA-synthesi~and enhance differentiation.

The relation of cancer risk tcconsumption of plant foods is prob­ably most usefully considered in anevolutionary/adaptational context. Theargument in this regard has beendeveloped in more detail elsewhere14.15.

SUPPLEMENTATION

As evidence emerged in the 1960sand 1970s of a role for vegetablesand fruits as protective agents, par­ticularly against stomach and lungcancers, a number of investigatorsbegan to ask about potential mecha­nisms and agents. The animal ex­perimental data were already sug­gesting the presence of a whole vari­ety of active agents but humans havealways liked simple solutions andmagic bullets16. Researchers wonderedwhether p-carotene might be the rel­evant agent17• They began with ret­inol data on humans and animals,but drifted to p-carotene as oxygendamage to DNA and antioxidant sta­tus became possible players incarcinogenesis. This nicely framedhypothesis was enough to spark awhole industry.

The hypothesis was boldly statedand testable, and a number of well­conducted studies have now renderedthe verdict. p-carotene supplementa­tion does not lower rates of lung can­cer18.19.20and among high-risk indi­viduals appears to increase incidenceand mortality18.19.p-carotene also doesnot reduce recurrence of adenomatous

pOlyps21 and may increase risk oflarger polyps22. ~-carotene does notreduce the risk of recurrence of skincancer23.

In striking contrast, as the con­stituents of tobacco smoke were enu­merated, it became increasingly clearthat making a noncarcinogenic ciga­rette was not an achievable goal andthat behavioural, economic and leg­islative programmes to eliminate smok­ing were more appropriate. It maysuggest that behavioural approaches(paralleling the successful tobaccoprogrammes) to increasing plant foodintake may be more fruitful. Economicincentives to increase human plant­food production are also worthy ofconsideration.

There are other arguments enu­merated above, based on the biology

of cancer, to support an increasedintake of plant foods as a primarystrategy. The use of single agentshas proved to be ineffectual and ulti­mately counterproductive in the treat­ment of many cancers; this is largelybecause resistant clones arise readilyin the presence of potent cytotoxic/chemotherapeutic agents. In rapidlyproliferating tissues, with elevated levelsof cell death, selection for survival inthe presence of the agent will occurrapidly. In tissues where there arelarge numbers of initiated cells, it isplausible that similar selection willhappen in the presence of a singlechemo-preventive agent.

If the action of the agent is toinduce differentiation, those cells thatare incapable of differentiation maygain a proliferative advantage. Simi­lar arguments apply to a single agentthat increases the rate of apoptoticcell death; again, those cells that areresistant to apoptosis may continueto proliferate24.

It follows that, while we shouldcontinue experimental studies to un­derstand the role of specific agentsin cancer prevention, we should notbe surprised if the effect of the agentdiffers at different stages ofcarcinogenesis or if it differs whenused alone vs in combination withother compounds.

The safest public health strat­egy seems to be to advocate increasedintake of intact plant foods with themultiplicity of agents that they con­tain. It is less likely that any clone ofmalignant cells can survive the poly­pharmacy of plant foods15,24.

IMPLICATIONS FOR INDIVIDUALSAND COMMUNITIES

The implication for individualsand societies around the world areclear - produce and eat more veg­etables and fruit - not more pills.

At present, it is not clear whatquantity we should eat each day - itis clear that many people around theworld do not eat enough. Therefore,setting a population target of per­haps 400 g may be a useful interimgoal. Certainly, at this level, there arefew dangers for any part of the popu­lation. In India, maintenance of thetraditional plant-based diet, at a levelof energy intake sufficient to ensurethe absence of childhood malnutri­tion, is, along with the avoidance of

tobacco use, likely to make a pro­found contribution to continuing thelow rates of cancer that are a featureof Indian health.

Excerpts from the Gopa/an Oration delivered

at the XXIXth Annual Meeting of the Nutrition Societyof India atthe National Institute of Nutrition, Hyderabad,on November 21, 1996.

The full text of the oration will appear in the

proceedings of the Nutrition Society of India.

References

1. Kohman, E.F.: The chemical components ofonion vapours responsible for wound-healing qualities.Science, 106:625-27, 1947.

2. Fenwick, G.R., Heaney, R.K. and Muller, W.J.:Glucosinolates and their breakdown products infoods and food plants. CRC Crit Rev Food Sci Nutr,18: 123-201, 1983.

3. Darby, W.J., Ghalioungui, P. and Grivetti, L.:Food: The gift of Osiris. Vo12, Academic Press Inc,New York, 1977.

4. Doll, R. and Peto, R.: The causes of cancer.Oxford University Press, New York, 1981.

5. Steinmetz, K.A. and Potter, J.D.: Vegetables,fruit and cancer. I. Epidemiology. Cancer Causesand Control, 2:325-57, 1991.

6. Steinmetz, K.A. and Potter, J.D.: Vegetables,fruit and cancer. II. Mechanisms. Cancer Causes

and Control, 2:427-42, 1991.

7. Steinmetz, K. and Potter J.D.: Vegetables, fruitand cancer prevention: A review. JADA, 96:1027­1039, 1996.

8. Stocks, P. and Karn, M.N.: A cooperative studyof the habits, home life, dietary and family historiesof 450 cancer patients and of an equal number ofcontrol patients. Ann Eugenics, 5:30-280, 1933.

9. Orr, I.M.: Oral cancer in betel nut chewers inTravancore. Its aetiology, pathology and treatment.Lancet, 2:575-580, 1933.

10. Correa, P., Fontham, E., Pickle, L.W., Chen, V.,Lin, V. and Haenszel, W.: Dietary determinants ofgastric cancer in Louisiana inhabitants. J Natl Can­cer Inst, 75:645-54, 1985.

11. Notani, P.N. and Jayant, K.: Role of diet inupper aerodigestive tract cancers. Nutr Cancer,10:103-13,1987.

12. Cook-Mozaffari, P.J., Azordegan, F., Day, N.E.,Ressicaud,A., Sabai,C.and Aramesh,B.: Oesophagealcancer studies in the Caspian littoral of Iran: resultsof a case-control study. Br J Cancer, 39:293-309,1979.

13. Koo, L.C.: Dietary habits and lung cancer riskamong Chinese females in Hong Kong who neversmoked. Nutr Cancer, 11:155-172, 1988.

14. Potter, J.D. and Graves, K.L.: Diet and cancer:Evidence and mechanisms - an adaptation argu­ment. Ed: Rowland, I.R. In: Nutrition, Toxicity andCancer. CRC Press, Boca Raton, 379-412, 1991.

15. Potter, J.D.: The epidemiology of diet and can­cer. Evidence of human maladaptation. Eds: Moon,T.E. and Micozzi, M.S. In: Nutrition and Cancer

Prevention. Investigating the Role of Macronutri­ents. Dekker, New York, 55-84, 1992.

16. Wattenberg, L.W.: Inhibition of chemical

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carcinogenesis.J Natl Cancer Inst, 60: 11-18, 1978.

17. Peto, R., Doll, R., Buckley, J. and Sporn, M.:Can dietary ~-carotene materially reduce humancancer rates? Nature, 290:201-208,1981.

18. Alpha-tocopherol, ~-carotene Cancer Preven­tion Study Group. The effect of vitamin E and ~­carotene on the incidence of lung cancer and othercancers in male smokers. N Engl J Med, 330: 1029­1035,1994.

19. Omenn, G., Goodman, G.,Thornquist, M.,Balmes,J., Cullen, M., Glass, A., Keogh, J., Meyskens, F.,Valanis, B., Williams, J., Barnhart, S. and Hammar,S.: Effects of a combination of ~-carotene andvitamin A on lung canc'er and cardiovascular dis­ease. N Engl J Med, 334: 1150-1155, 1996.

20. Hennekens, C.H., Buring, J., Manson, J., Stampfer,M., Rosner, B., Cook, N., Belanger, C., LaMoke, F.,Gaziano, JM., Ridker, P., Willett, W. and Peto, R.:Lack of effect of long-term supplementation with~­carotene on the incidence of malignant neoplasmsand cardiovascular disease.N Engl J Med, 334: 1145­1149,1996.

21. Greenberg, E.R., Baron, J., Tosteson, T., Free­man, D., Beck, G., Bond, J., Colacchio, T., Coller,J., Frankl, H., Hail, R., Mandel, J., Nierenberg, D.,Rothstein, R., Snover, D., Stevens, M., Summers,R. and van Stolk, R.: A clinical trial of antioxidantvitamins to prevent colorectal adenoma. N Engl JMed, 331:141-147,1994.

22. MacLennan, R., Macrae, F., Bain, C., Battistutta,D., Chapuis, P., Gratten, H.,eta/.: Randomised trialof intake of fat, fibre and ~-carotene to preventcolorectal adenomas. J Natl Cancer Inst, 87: 1760­1766, 1995.

23. Greenberg, E.R., Baron, J., Stukel~T., Stevens,. M., Mandel, J., Spencer S., Elias, P., Lowe, N.,Nierenberg, D., Bayrd, G., Vance, J.C., Freeman,D., Clendenning, W. and Kwan, T.: A dinical trial of~-carotene to prevent basal-cell and squamous­cell cancers of the skin.N EnglJ Med, 323:789-795,1990.

24. Potter, J.D.: Chemoprevention: pl<larmacologyor biology. Oncology, 10:1487-1488, 1996.

NUTRITIONNEWS

• International Symposium by RankPrize Funds: This Symposium on:'Feeding a World Population of morethan Eight Billion People: A Chal­lenge to Science' was held in the UKfrom December 6-9, 1996. It was at­tended by 104 delegates. The pro­ceedings are expected to be pub­lished shortly.

• The 23rd Kamla Puri SabharwalMemorial Lecture was held on De­cember 18, 1996, at the Lady IrwinCollege. Dr Prema Ramachandranspoke on: 'Current Concerns inMaternal Nutrition'. Dr C. Gopalanpresided.