Studies of migrants

People who migrate from one country to another provide an excellent opportunity to study the effects of dietary and environmental factors on disease; their first-degree relatives who have not migrated provide a genetically matched control group for comparison.

Both breast and prostate cancer are rare in China and Japan compared with the

R = 0.945

;

*

;

%

;

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• •

• t

40 60 80 100 120 140 16

Figure 7.1 International correlation between fat intake and breast cancer in women. From data reported by CarollKK (1975) Cancer Research 35: 3374-3383.

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IF

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plasma vitamin E, pmol /L

Figure 7.2 The relationship between plasma vitamin E levels and coronary heart disease. From data reported by Gey KF et al. (1991) American Journal of Clinical Nutrition 53 (supplement 1): 326-334s.

incidence of both in USA. Figure 7.3 shows that people who have migrated from China and Japan to Hawaii or San Francisco have a considerably higher incidence of both cancers than their relatives who did not migrate and retained their traditional diet and lifestyle.

Similar studies of adult immigrants in the mid-twentieth century from Poland (where gastric cancer was common and colorectal cancer rare) to Australia (where gastric cancer is rare and colorectal cancer relatively common) found a significant increase in colorectal cancer among the immigrants, whereas the incidence of gastric cancer remained at the relatively high Polish level (although second-generation Polish-Australians have the low Australian incidence of gastric cancer (Figure 7.4). This suggests that dietary or environmental factors involved in the development of colorectal cancer may act relatively late in life, whereas factors that predispose to gastric cancer act earlier in life.

7.2.4 CASE-CONTROL STUDIES

A more precise technique for studying relationships between diet and disease is to compare people suffering from the disease with disease-free subjects who are matched as closely as possible for gender, ethnicity, age, lifestyle and as many other factors as possible. Figure 7.5 shows the results of a series of such case—control studies, which show that the serum concentration of P-carotene (section 7.4.3.4) is significantly lower in people with a variety of cancers than in disease-free control subjects. Such data have been widely interpreted as suggesting that P-carotene has a protective effect

Figure 7.3 Cancer of the breast and prostate in Chinese andJapanese immigrants to the U SA compared with incidence of the diseases in first-degree relatives in China and Japan and the local population in the USA (SFO, San Francisco). From data reported by Haenzel W and Kurihawa M (1965) Journal of the National Cancer Institute 40: 43—68. and Yu FL et al. (1991) International Journal of Epidemiology 20: 76-81.

Figure 7.4 Gastric and colorectal cancer in Polish immigrants to Australia compared with rates in Poland and among the local population in Australia. Prom data reported by StaszetvskiJ et al. (1971)British Journal of Cancer 25: 599-610, and McMichael AJ et al. (1980) International Journal of Cancer 25: 431-437.

Figure 7.5 The relationship between plasma carotene and various cancers — case—control studies. From data reported by Peto R et al (1981) Nature 290: 201-208.

against a variety of cancers; equally, it could be interpreted as suggesting that a variety of cancers affect carotene metabolism.

7.2.5 PROSPECTIVE STUDIES

Once dietary factors that seem to pose a hazard or offer a protective effect have been identified by the types of study discussed above, the next step is to undertake a prospective study. In these studies, a group of people are grouped according to their status with respect to the nutrient in question then followed for 5—10 or more years to see whether there is any significant difference in disease incidence between people with high or low intakes of the nutrient in question. Figure 7.6 shows the results of such a prospective study in which people were grouped according to their plasma

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quintile of serum carotene

Figure 7.6 The relationship between plasma carotene and lung cancer — a prospective study. From data • Peto R et al. (1981) Nature 290: 201—208.

quintile of serum carotene

Figure 7.6 The relationship between plasma carotene and lung cancer — a prospective study. From data • Peto R et al. (1981) Nature 290: 201—208.

concentration of P-carotene; those with the lowest initial concentration of serum carotene were 2.2 times more likely to die from lung cancer during the study period than those with the highest concentration. As with the case—control studies (Figure 7.5) this suggests a protective effect of P-carotene, but in this case the subjects were presumably free from cancer at the beginning of the study, so there is not the confounding problem that the disease may have affected carotene metabolism rather than carotene affecting the chance of developing cancer.

7.2.6 INTERVENTION STUDIES

The next step is to test the hypothesis derived, from epidemiological and prospective studies, that a change in diet, or provision of a nutritional supplement, will reduce the risk of developing a disease. Figure 7.7 shows the results of such an intervention trial in Finland in the 1980s to test the protective effect of P-carotene against lung cancer. Altogether some 10,000 people were involved — half received supplements of P-carotene and half did not, and they were followed for 5—10 years. The results were disappointing — not only did the supplements not reduce the incidence of lung cancer in the test group, but there was an increased incidence of lung, prostate and bladder cancer among those receiving P-carotene. A similar intervention trial of P-carotene in USA was terminated early because of the increased incidence of cancer among those receiving the supplements.

Figure 7.7 The effects of P-carotene supplementation on death from lung and other cancers. From data reported by the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group (1994) New England Journal of Medicine 330: 1029-1035.
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