Cancer 3-carotene

Thus, it is uncertain to what extent the apparent protective effects of fruit and vegetable consumption on risk of stomach cancer can be attributable to their phytoestrogen content. This appears not to have been studied directly, and other constituents such as ascorbic acid (vitamin C), a-tocopherol (vitamin E) and /1-carotene may be potentially protective. 

An alkene, sometimes caJled an olefin, is a hydrocarbon that contains a carbon-carbon double bond. Alkenes occur abundantly in nature. Ethylene, for instance, is a plant hormone that induces ripening in fruit, and o-pinene is the major component of turpentine. Life itself would be impossible without such alkenes as /3-carotene, a compound that contains 11 double bonds. An orange pigment responsible for the color of carrots, /3-carotene is a valuable dietary source of vitamin A and is thought to offer some protection against certain types of cancer. 

Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or (3-carotene, the results were ambiguous and the causes are still being debated. 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

The third study was the Physicians Health Study, in which 22,071 US male physicians were randomised to get either 50 mg P-carotene or 325 mg aspirin, or both, or neither, every other day for 12 years. There was no evidence of a significant beneficial or harmful effect on cancer or cardiovascular... 

ALBANES D, HEINONEN O P, HUTTUNEN J K, TAYLOR P R, VIRTAMA J, EDWARDS B K, HAAPAKDSKI J, RAUTALATHI M, HARTMAN A M and PALMGREN J (1995) Effects of alpha-tocopherol and beta carotene supplements on cancer incidence in the alpha-tocopherol beta-carotene cancer prevention study , Am J Clin Nutr, 62, 1427S-30S. 

ALPHA-TOCOPHEROL BETA-CAROTENE (ATBC) CANCER PREVENTION STUDY GROUP (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers , New Engl J Med, 330, 1029. 

VAN POPPED G and goldbohm r a (1995) Epidemiological evidence for heta-carotene and cancer prevention , J Am Clin Nutr, 62, 1393S-402S. 

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

OMENN G S, GOODMAN G E, THORNQUIST M D, BALMES J, CULLEN M R, GLASS A, KEOGH J P, MEYSKENS F L, VALANIS B, WILLIAMS J H, BARNHART S and HAMMAR S (1996) Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N EnglJ Med 1150-1155. 

ALBANES D, HEiNONEN o p, TAYLOR p R, et uL, (1996) a-tocopherol and P-carotene supplementation and Irmg cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study effect of base-line chacteristics and study compliance. J Natl Cancer Inst. 88 1560-70. 

OMENN G s, GOODMAN G E, THORNQUIST M, et al., (1996) Risk factors for limg cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst. 88 1550-59. 

Many epidemiological studies have analyzed the correlations between different carotenoids and the various forms of cancer and a lot of conclusions converge toward protective effects of carotenoids. Many studies were carried out with (i-carotene. The SUVIMAX study, a primary intervention trial of the health effects of antioxidant vitamins and minerals, revealed that a supplementation of p-carotene (6 mg/day) was inversely correlated with total cancer risk. Intervention studies investigating the association between carotenoids and different types of cancers and cardiovascular diseases are reported in Table 3.1.2 and Table 3.1.3. 

Carotenoids and prostate cancer — Numerous epidemiological studies including prospective cohort and case-control studies have demonstrated the protective roles of lycopene, tomatoes, and tomato-derived products on prostate cancer risk other carotenoids showed no effects. " In two studies based on correlations between plasma levels or dietary intake of various carotenoids and prostate cancer risk, lycopene appeared inversely associated with prostate cancer but no association was reported for a-carotene, P-carotene, lutein, zeaxanthin, or p-cryptoxanthin. - Nevertheless, a protective role of all these carotenoids (provided by tomatoes, pumpkin, spinach, watermelon, and citrus fruits) against prostate cancer was recently reported by Jian et al. ... 

Womens Health Study 50 mg/alternate days, 2.1 yr P-Carotene Lung cancer 0 38... 

Primary prevention trial (Alpha-Tocopherol, 20 mg/day, 5 to 8 yr P-Carotene Lung cancer -t 35... 

Beta-Carotene Cancer Prevention Study) Gastric cancer 0 45... 

Placebo-controlled chemoprevention trial 30 mg/day carotene + 25,000 lU P-Carotene Lung cancer and total mortality + 36... 

Primary prevention trial (Physicians Health 20 mg/alternate days, 12 yr P-Carotene Lung cancer risk 0 37... 

Study) Primary prevention trial 6 mg/day beta-carotene, 7.5 years, P-Carotene Total cancer risk 15... 

No association. - = Inverse association. + = Positive association. ATBC = a-Tocopherol, p-Carotene Cancer Prevention Study. PSA = Prostate-specific antigen. 

Primary prevention trial (a-Tocopherol, 5-Carotene Cancer Prevention Study)... 

Carotenoids and breast cancer — Among seven case-control studies investigating the correlation between different carotenoid plasma levels or dietary intakes and breast cancer risk, five showed significant inverse associations with some carotenoids. - In most cases, this protective effect was due to 3-carotene and lutein. However, one (the Canadian National Breast Screening Study ) showed no association for all studied carotenoids including (I-carotene and lutein. More recently, another study even demonstrated a positive correlation between breast cancer risk and tissue and serum levels of P-carotenes and total carotenes. Nevertheless, these observational results must be confirmed by intervention studies to prove consistent. 

Carotenoids and urino-digestive cancers — On the whole, findings from epidemiological studies did not demonstrate a protective role of carotenoids against colorectal, gastric, and bladder cancers. Indeed, most prospective and case-control studies of colorectal cancer showed no association with dietary intake or plasma level of most carotenoids. - Only lycopene and lutein were shown to be protective against colorectal cancer. Otherwise, findings from the ATBC study s showed no effect of P-carotene supplementation on colorectal cancer. 

Data concerning gastric cancer are scarce. The prospective Netherlands Cohort Study found no correlation between lutein dietary intake and gastric cancer risk, whereas findings from the Physicians Health Study and the ATBC study reported no effect of P-carotene on gastric cancer incidence. Two case-control studies and three intervention trials (ATBC, CARET, and the Physicians Health Study ) showed no association of P-carotene, lycopene, lutein, zeaxanthin, and P-cryptoxanthin. 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

Epidemiological data on carotenoids and cerebral infarcts or strokes indicate a protective effect of P-carotene and lycopene. Indeed, the Basel prospective study, the Kuopio Ischaemic Heart Disease Risk Factor study, and the Physicians Health Study " have shown an inverse correlation between carotenoid plasma level and risk of stroke. In the same way, Hirvonen et al. demonstrated, in findings from the ATBC cancer prevention stndy, an inverse association between P-carotene dietary intake and stroke. However, clinical data on carotenoids and stroke are nonexistent and they are needed to confirm this possible protective effect of carotenoids on stroke. 

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