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Medical Forum / Diseases and Disorders / Prostate Cancer / May 2007Study: Tomatoes no defense against prostate cancer
This is being crossposted to sci.med.diseases.cancer (FYI) J http://seattlepi.nwsource.com/local/316050_tomato17.html Last updated May 16, 2007 10:47 Study: Tomatoes no defense against prostate cancer By TOM PAULSON P-I REPORTER Heinz might no longer be able to claim its ketchup can prevent prostate cancer. The FDA-approved and popularly held notion that antioxidants in tomatoes can prevent prostate cancer appears to be false, according to a large study done by the Fred Hutchinson Cancer Research Center and National Cancer Institute. "It was an hypothesis based on observational studies and the fact that cancer can be caused by oxidative damage to DNA," said Ulrike Peters, a Fred Hutchinson scientist and lead author on the report published in the current journal of Cancer Epidemiology, Biomarkers and Prevention. Natural dietary compounds known as carotenoids, especially the antioxidant lycopene, have been proposed as cancer-fighters because of their ability to protect against the kind of chemical and genetic "oxidative" damage in cells that can lead to cancer. Tomatoes are especially high in lycopenes and some earlier studies, including one done in 2002 by Harvard, found epidemiological evidence that men who ingested large amounts of tomato products had lower risks of prostate cancer. This, along with other studies suggesting the protective benefit, prompted the Food and Drug Administration in 2005 to allow the world's largest maker of tomato-based products, H.J. Heinz Co., to advertise that: "The risk of prostate cancer may be reduced by eating just 1/2 to 1 cup of tomatoes -- such as a single serving of Classico{+?} pasta sauce -- per week." The FDA now allows makers of tomato-based products to claim their foodstuffs may reduce the risk of gastric, ovarian and pancreatic cancers as well. Peters said their study examined only prostate cancer because this has been the primary target of most such claims. Rather than assessing dietary practices, she and her colleagues examined the blood levels of carotenoids in 28,000 men between 55 and 74. Peters and her colleagues not only failed to find a positive association between high levels of the antioxidants and lower rates of prostate cancer, they found that the men who had high blood levels of lycopenes (those who might have eaten lots of tomato products) were the ones with the most aggressive form of prostate cancer. "It certainly raises a question," said Peters, who noted that other studies have shown the equally counterintuitive finding that high levels of beta carotene can increase the risk of lung cancer or heart attacks in smokers. It's not certain that high levels of lycopene raise the risk of prostate cancer, Peters said, or what effect these antioxidants may have on other cancers. "But the basic mechanism is the same for all cancers," Peters said. There's no reason to believe that lycopenes would be any more protective against other forms of cancer, she said. "It's disappointing, really, because it would have been such a simple preventive measure." ________________________________________ More Hutchison Centre prostate cancer research is here http://www.fhcrc.org/research/diseases/prostate_cancer/ including $12.7 million federally funded project to investigate prostate-cancer progression. and A large international study is underway to determine if vitamin E and the trace element selenium, taken together or separately, can prevent prostate cancer. $180 million, federally funded Selenium and Vitamin E Cancer Prevention Trial (SELECT) has enlisted more than 34,000 men through a network of 400 research sites in North America. Seems to me a lot of money going into research for questions that answers are already known. Normal cells mutate and spread and continue mutating. Assuming that similar research projects and money are being spent in every center, in the US Wouldn't it be better to spend this money on health/or cancer coverage for all, in the US? And/or other education/employment creation incentives? J >This is being crossposted to sci.med.diseases.cancer (FYI) >J [quoted text clipped - 49 lines] >(those who might have eaten lots of tomato products) were the ones with >the most aggressive form of prostate cancer. Seems to be yet another example the notorious inaccuracy of news reports about medical studies. The study's reference is Serum Lycopene, Other Carotenoids, and Prostate Cancer Risk: a Nested Case-Control Study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Ulrike Peters Michael F. Leitzmann, Nilanjan Chatterjee, Yinghui Wang1, Demetrius Albanes, Edward P. Gelmann4, Marlin D. Friesen, Elio Riboli and Richard B. Hayes Cancer Epidemiology Biomarkers & Prevention 16, 962-968, May 1, 2007. doi: 10.1158/1055-9965.EPI-06-0861 <http://cebp.aacrjournals.org/cgi/content/abstract/16/5/962> Abstract: "Background: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancerpreventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive. Materials and Methods: We investigated the association between prediagnostic serum carotenoids (lycopene, {alpha}- carotene, ß-carotene, ß-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score =7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under nontrial conditions. Results: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). ß-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk. Conclusion: In this large prospective study, high serum ß- carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention. (Cancer Epidemiol Biomarkers Prev 2007;16(5):9628)" As we can see from the abstract, it was it was beta-carotene, which was associated with increased risk of aggressive prostate cancer, not lycopene. The EurekAlert news report No magic tomato? Study breaks link between lycopene and prostate cancer prevention <http://www.eurekalert.org/pub_releases/2007-05/aafc-nmt051607.php> gets it right: "Most surprisingly, says Peters, was the relationship between increased risk of aggressive prostate cancer defined as disease that has spread beyond the prostate and beta- carotene, another antioxidant found in many vegetables and commonly used as a dietary supplement. This unexpected observation "may be due to chance, however beta carotene is already known to increase risk of lung cancer and cardiovascular disease in smokers," Peters said."  SignatureMatti Narkia > >This is being crossposted to sci.med.diseases.cancer (FYI) > >J [quoted text clipped - 130 lines] > beta carotene is already known to increase risk of lung > cancer and cardiovascular disease in smokers," Peters said. Tomatoes have beta-carotene in them. http://ars.usda.gov/is/pr/1998/981102.htm J >> >This is being crossposted to sci.med.diseases.cancer (FYI) >> >J [quoted text clipped - 134 lines] >http://ars.usda.gov/is/pr/1998/981102.htm >J Sure they do ;-) SignatureMatti Narkia >>> >This is being crossposted to sci.med.diseases.cancer (FYI) >>> >J [quoted text clipped - 135 lines] >>J >Sure they do ;-) But they are not the best source of beta-carotene, which appears in many, many vegetables. Therefore we cannot say that tomatoes are associated with increased risk of aggressive prostate cancer on the basis of this study. Tomato consumption was not measured in this study. This study found no association with lycopene and total prostate cancer and also no association with lycopene and aggressive prostate cancer. So although no causal conclusion can be drawn from an epidemiological study like this, the results of the study suggest that lycopene may not prevent prostate cancer. But they also suggest that lycopene does no harm either, it does not seem to make prostate cancer more aggressive. Lycopene is found in tomatoes, watermelons and some othe plants. We cannot really for sure say where the lycopene measured in the serum of the participants came, because food consumption was not investigated. But tomatoes are perhaps the most commonly used lycopene-rich food item, so it may be justified to make some tentative _speculations_ about tomatoes on the basis of this study. However, the results of this study should be compared with the earlier lycopene and tomato studies. Perhaps I try to that later on. SignatureMatti Narkia >>>> >This is being crossposted to sci.med.diseases.cancer (FYI) >>>> >J >>>> >http://seattlepi.nwsource.com/local/316050_tomato17.html >>>> >Last updated May 16, 2007 10:47 >>>> >Study: Tomatoes no defense against prostate cancer [snip] >>>> Seems to be yet another example the notorious inaccuracy of news >>>> reports about medical studies. The study's reference is [quoted text clipped - 8 lines] >>>> doi: 10.1158/1055-9965.EPI-06-0861 >>>> <http://cebp.aacrjournals.org/cgi/content/abstract/16/5/962> [snip] >>>> Conclusion: In this large prospective study, high serum ß- >>>> carotene concentrations were associated with increased risk [quoted text clipped - 8 lines] >>>> was associated with increased risk of aggressive prostate cancer, not >>>> lycopene. [snip] >But they are not the best source of beta-carotene, which appears in >many, many vegetables. Therefore we cannot say that tomatoes are [quoted text clipped - 16 lines] >this study should be compared with the earlier lycopene and tomato >studies. Perhaps I try to that later on. This is a rather long post, sorry about that. I searched and found some earlier studies. First, there is an earlier prospective epidemiological study from the same research team, published in the same paper in January last year. This study did not use blood work, but investigated food consumption with food frequency questionnaires. The reference is Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA, Crawford ED, Hayes RB. A prospective study of lycopene and tomato product intake and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):92-8. PMID: 16434593 [PubMed - indexed for MEDLINE] <http://cebp.aacrjournals.org/cgi/content/full/15/1/92> (free full text) Abstract: "BACKGROUND: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association.METHODS: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up.RESULTS: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95% CI, 0.57-1.16 for > or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (P(trend)=0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)= 0.15; lasagna, P(trend)=0.02).CONCLUSIONS: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration. (Cancer Epidemiol Biomarkers Prev 2006;15(1):92-8)." Excerpts from the discussion chapter (if you don't have time to read the whole study, read at least the abstract and the whole discussion chapter): "In this large prospective study, we found no overall association between prostate cancer risk and dietary intake of either lycopene or total tomato products. Although not statistically significant, inverse trends were found with pizza consumption, for all prostate cancer; with lycopene, for nonadvanced cancer; and with pizza and spaghetti sauce, for advanced disease. We also noted that lycopene and pizza were inversely associated with risk among those with a family history of prostate cancer. Results from a recent meta-analysis of 11 case-control studies and 10 cohort studies indicated that serum lycopene (RR, 0.74; 95% CI, 0.59-0.92 for the high versus low levels) was associated with a greater reduction in prostate cancer risk than dietary lycopene (RR, 0.89; 95% CI, 0.81-0.98 for the high versus low intake), whereas cooked tomato products (RR, 0.81; 95% CI, 0.71-0.92 for high versus low intake) were associated with greater risk reduction than raw tomato products (RR, 0.89; 95% CI, 0.80-1.00 for high versus low intake), although reductions in risk were modest in all instances (23). Results from the meta-analysis were not stratified by degree of disease progression; however, others suggest that high serum lycopene is inversely associated, in particular, with risk of aggressive prostate cancer (4, 11, 13). The weak inverse association noted in the meta-analysis with increased dietary lycopene was driven largely by data from the Health Professionals' Follow-up Study (RR, 0.84; 95% CI, 0.73-0.96; ref. 4). Data on plasma lycopene from this cohort (published subsequent to the meta-analysis) do not indicate an association with prostate cancer risk overall (43). In contrast to our subgroup findings for dietary lycopene, the Health Professionals' Follow-up Study cohort found an inverse association for plasma lycopene among participants ages =65 years and those without a family history of prostate cancer (43), and a stronger inverse association for dietary lycopene among men ages =65 years (4). Findings from three prospective studies yielded conflicting results with respect to raw tomato intake, with two finding a significant inverse association for high raw tomato intake (refs. 3, 44; RR, 0.57 and 0.74, respectively) and the third finding no overall association (RR, 1.00 per 25 g increase; ref. 14). In the Health Professionals' Follow-up Study cohort, processed tomato products (e.g., spaghetti sauce; ref. 4) and pizza (44) were evaluated showing strong inverse associations; certain risk estimates seemed to be more pronounced for advanced prostate cancer (4, 44). Our study is the only other prospective evaluation of processed tomato products and does not provide strong corroboration; however, case-control studies have indicated cooked tomato products as generally stronger predictors of reduced risk (7-9). Tomato products consumed in oil, such as pizza (7.5 g fat per serving), spaghetti/tomato sauce (14.6 g), and lasagna (23.8 g), are particularly bioavailable lycopene sources, due to greater intestinal absorption in association with fat. With the exception of chili, which is also typically high in fat (16.5 g/serving), none of the other main contributors to tomato intake assessed in our study had comparable amounts of fat (range, 0.16-4.7 g/serving). Heating processes enhance lycopene bioavailability by rupture of plant cell walls (30, 45) and transformation from the trans- to cis-isomer, which is more readily absorbed in the gut (27, 45-47). Lycopene in fresh tomatoes occurs almost entirely in the trans-form. In the prostate, 80% to 90% of lycopene is in the cis-form (48). Yet, our study found only weak relationships between oil content or cooking of tomato products and prostate cancer risk. Lycopene may protect prostate tissue from oxidative DNA damage by limiting cellular free radical exposure (49); however, tomatoes and tomato products also contain other carotenoids and phytochemicals (50), which may confer protection (51, 52). In an experimental feeding study (53), rats fed whole tomato powder were less likely to die from prostate cancer compared with rats fed synthetic lycopene, perhaps implicating other active components of tomatoes. [...] The apparent protective effects that we observed were neither strong nor consistent and do not provide compelling evidence that lycopene or tomato products in various forms protects from prostate cancer. Cooking process and concurrent consumption of fat might be necessary for the putative benefits of tomato products to be realized, however, increased lycopene or tomato product intake is unlikely, in itself, to represent a substantive preventive measure for prostate cancer." And here some other earlier studies, many of them have the full text available free of charge, so the reference lists are available, you can use them to find more related studies: Jian L, Lee AH, Binns CW. Tea and lycopene protect against prostate cancer. Asia Pac J Clin Nutr. 2007;16 Suppl 1:453-7. PMID: 17392149 [PubMed - in process] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17392149> "Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men. Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake." Jatoi A, Burch P, Hillman D, Vanyo JM, Dakhil S, Nikcevich D, Rowland K, Morton R, Flynn PJ, Young C, Tan W; North Central Cancer Treatment Group. A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II study from the North Central Cancer Treatment Group. Urology. 2007 Feb;69(2):289-94. PMID: 17320666 [PubMed - indexed for MEDLINE] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17320666> "... CONCLUSIONS: Lycopene, as prescribed in our study, did not appear effective for androgen-independent prostate cancer. The patients' reasons for enrolling in this trial were positive and realistic." Ellinger S, Ellinger J, Stehle P. Tomatoes, tomato products and lycopene in the prevention and treatment of prostate cancer: do we have the evidence from intervention studies? Curr Opin Clin Nutr Metab Care. 2006 Nov;9(6):722-7. Review. PMID: 17053426 [PubMed - indexed for MEDLINE] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17053426> Clark PE, Hall MC, Borden LS Jr, Miller AA, Hu JJ, Lee WR, Stindt D, D'Agostino R Jr, Lovato J, Harmon M, Torti FM. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy. Urology. 2006 Jun;67(6):1257-61. PMID: 16765186 [PubMed - indexed for MEDLINE] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=R etrieve&dopt=abstractplus&list_uids=16765186> "... CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA." Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002 Mar 6;94(5):391-8. PMID: 11880478 [PubMed - indexed for MEDLINE] <http://jnci.oxfordjournals.org/cgi/content/full/94/5/391> (free full text) "... CONCLUSION: Frequent consumption of tomato products is associated with a lower risk of prostate cancer. The magnitude of the association was moderate enough that it could be missed in a small study or one with substantial errors in measurement or based on a single dietary assessment. [...] We have confirmed an earlier reported (5) association between lycopene and tomato sauce intake and a reduced risk of prostate cancer in the HPFS. The initial observation was based on 773 case patients from 1986 to 1992; we then analyzed 2481 case patients from 1986 to 1998. Our findings were highly unlikely to result from chance because similar associations were observed regarding tomato sauce intake and reduced risk of prostate cancer for independent time periods using different questionnaires. Recall bias is unlikely in a prospective study. PSA screening use was uniform across levels of tomato sauce intake, and restricting analysis to men who had PSA tests did not change the results. Thus, appreciable detection bias probably did not occur. [...] Overall, data suggest that the intake of tomatoes and tomato products is associated with a decreased risk of prostate cancer. This benefit may be related to the antioxidant properties of lycopene, but other potential mechanisms and other beneficial tomato-based components instead of or combined with lycopene cannot be excluded (45). Of note, the survival of rats with prostate cancer induced by N-methyl-N- nitrosurea and testosterone was increased slightly by lycopene supplementation (17% increase; P = .16) but more so by tomato powder (39% increase; P = .0056) (46). Because current evidence is not definitive, other lines of evidence are needed to provide confirmatory information. A long-term large randomized trial with prostate cancer as the endpoint would be most informative, but short-term trials using endpoints such as prostate cancer recurrence or intermediate endpoints may be more feasible. On the basis of our results, future epidemiologic studies, to be maximally informative, should examine populations with relatively high intakes of tomato products, be sufficiently large to evaluate moderate relative risks, have a comprehensive assessment of major lycopene sources, account for bioavailability of lycopene, account for temporal patterns (as a single dietary or blood assessment, particularly in studies with long follow-up periods, may be inadequate), and examine a wide range of age groups. From the available data, we suggest that increased consumption of tomato and tomato-based products may be prudent; such a recommendation is consistent with current health guidelines to increase fruit and vegetable consumption. Efficacy and safety of pills containing only lycopene, however, would need to be specifically evaluated." Canene-Adams K, Campbell JK, Zaripheh S, Jeffery EH, Erdman JW Jr. The tomato as a functional food. J Nutr. 2005 May;135(5):1226-30. PMID: 15867308 [PubMed - indexed for MEDLINE] <http://jn.nutrition.org/cgi/content/full/135/5/1226> (free full text) "CONCLUSIONS Emerging epidemiological evidence regarding lycopene, tomatoes, and CVD has shown promising protective effects with more frequent consumption. Epidemiology, in vitro studies, animal studies, and small clinical human trials all provide support for significant effects of tomato consumption on prostate cancer development, although many questions still remain. For example, the mechanistic action of tomato components, including lycopene and other carotenoids, and their interactions with each other warrants further investigation. Scientists should be mindful that tomato products contain a variety of compounds in addition to lycopene, such as vitamins C and E, soluble fiber, other carotenoids, and polyphenols. Moreover, health effects derived from tomato components could also be due in part to the effects of the metabolic products of these bioactive compounds. Research is required to determine how tomato phytochemicals interact with other food components, such as sulforophane in broccoli, isoflavones in soy, and various herbal products. Only then can we truly understand the disease prevention capabilities of tomatoes and how to properly process and consume tomato products for maximal health benefits. Due to the large volume of tomatoes that Americans consume, tomatoes are a convenient matrix by which nutrients and bioactive components can be delivered for human consumption (38). Overall, no matter if you are trying to reduce the risk of CVD or prostate cancer, a diet that regularly contains tomatoes appears to be a healthy choice and beneficial for us all." Campbell JK, Canene-Adams K, Lindshield BL, Boileau TW, Clinton SK, Erdman JW Jr. Tomato phytochemicals and prostate cancer risk. J Nutr. 2004 Dec;134(12 Suppl):3486S-3492S. Review. PMID: 15570058 [PubMed - indexed for MEDLINE] <http://jn.nutrition.org/cgi/content/full/134/12/3486S> (free full text) Etminan M, Takkouche B, Caamano-Isorna F. The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):340-5. PMID: 15006906 [PubMed - indexed for MEDLINE] <http://cebp.aacrjournals.org/cgi/content/full/13/3/340> (free full text) "PURPOSE: To determine whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. METHODS: We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies. Log relative risks (RRs) were weighed by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). Logistic regression and Poisson regression analyses were used to determine the effect produced by a daily intake of one serving of tomato product. RESULTS: Eleven case- control studies and 10 cohort studies or nested case-control studies presented data on the use of tomato, tomato products, or lycopene and met our inclusion criteria. Compared with nonfrequent users of tomato products (1st quartile of intake), the RR of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80-1.00). For high intake of cooked tomato products, this RR was 0.81 (95% CI 0.71-0.92). The RR of prostate cancer related to an intake of one serving/day of raw tomato (200 g) was 0.97 (95% CI 0.85-1.10) for the case-control studies and 0.78 (95% CI 0.66-0.92) for cohort studies. CONCLUSIONS: Our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest and restricted to high amounts of tomato intake. Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer." SignatureMatti Narkia >>>>> >This is being crossposted to sci.med.diseases.cancer (FYI) >>>>> >J [quoted text clipped - 16 lines] >>>>> doi: 10.1158/1055-9965.EPI-06-0861 >>>>> <http://cebp.aacrjournals.org/cgi/content/abstract/16/5/962> [snip] >Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, >Urban DA, Crawford ED, Hayes RB. [quoted text clipped - 4 lines] ><http://cebp.aacrjournals.org/cgi/content/full/15/1/92> (free full >text) [snip] >And here some other earlier studies, many of them have the full text >available free of charge, so the reference lists are available, you [quoted text clipped - 5 lines] >PMID: 17392149 [PubMed - in process] ><http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17392149> [snip] >Jatoi A, Burch P, Hillman D, Vanyo JM, Dakhil S, Nikcevich D, Rowland >K, Morton R, Flynn PJ, Young C, Tan W; North Central Cancer Treatment [quoted text clipped - 5 lines] >PMID: 17320666 [PubMed - indexed for MEDLINE] ><http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17320666> [snip] >Ellinger S, Ellinger J, Stehle P. >Tomatoes, tomato products and lycopene in the prevention and treatment [quoted text clipped - 11 lines] >PMID: 16765186 [PubMed - indexed for MEDLINE] ><http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=R etrieve&dopt=abstractplus&list_uids=16765186> [snip] >Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. >A prospective study of tomato products, lycopene, and prostate cancer [quoted text clipped - 3 lines] ><http://jnci.oxfordjournals.org/cgi/content/full/94/5/391> (free full >text) [snip] >Canene-Adams K, Campbell JK, Zaripheh S, Jeffery EH, Erdman JW Jr. >The tomato as a functional food. >J Nutr. 2005 May;135(5):1226-30. >PMID: 15867308 [PubMed - indexed for MEDLINE] ><http://jn.nutrition.org/cgi/content/full/135/5/1226> (free full text) [snip] >Campbell JK, Canene-Adams K, Lindshield BL, Boileau TW, Clinton SK, >Erdman JW Jr. [quoted text clipped - 11 lines] ><http://cebp.aacrjournals.org/cgi/content/full/13/3/340> (free full >text) Some additional studies and articles; Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res. 1999 Mar 15;59(6):1225-30. PMID: 10096552 [PubMed - indexed for MEDLINE] <http://cancerres.aacrjournals.org/cgi/content/full/59/6/1225> (free full text) Abstract: "Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer." Excerpts from the discussion chapter: "In this prospective analysis of plasma antioxidant levels, lycopene was the only compound that appeared to have a significant and internally consistent association with development of prostate cancer. It is important to note that our study was conducted among participants in a randomized trial involving ß-carotene supplements and that the relationship of plasma lycopene level to prostate cancer risk clearly appeared to depend on whether ß-carotene supplements were consumed. The inverse association between lycopene and risk was confined to men not randomly assigned to take ß- carotene supplements. Moreover, although lycopene might be the most important dietary carotenoid in this context, our results indicate that for men in the highest risk category due to low lycopene levels, a risk reduction similar to that obtained with high lycopene level might be achieved with a high-dose ß-carotene supplement. In fact, the average risk reduction (relative to the group with lowest lycopene and placebo) for all prostate cancers across all lycopene quintiles in the ß-carotene group was 37.3%, very close to the 41% risk reduction observed for placebo group men with the highest lycopene. Taken together, these less-than- additive joint effects are consistent with the hypothesis that there is a ceiling on the benefit gained by consumption of these carotenoids and that this ceiling might be reached either through high dietary lycopene intake or regular use of ß-carotene supplements that raise plasma ß-carotene to very high levels. This interpretation lends indirect support for antioxidant activity as the mechanism of action because of evidence cited earlier that lycopene shares antioxidant properties with ß-carotene but has higher antioxidant potency and capacity based on in vitro and in vivo studies. The potential importance of diverse antioxidants in prostate cancer development is further supported by recent results indicating decreased prostate cancer incidence among men with increased exposure to selenium and vitamin E supplements (12, 13, 14) . Our results for plasma lycopene levels are strikingly similar to those we obtained in a recent analysis of dietary intake and prostate cancer occurrence during 6 years of follow-up in the Health Professionals Follow-up Study (3) . In that study, the relative risk of prostate cancer (excluding stage A1) for men in the highest quintile of total lycopene intake compared to the lowest was 0.79 (95% CI = 0.640.99). The relative risk of advanced prostate cancer (stage C or D) was 0.57, close to that obtained here, for men with the highest lycopene score, which was based on plasma levels predicted by dietary intake. The strongest inverse associations were observed in men who frequently consumed cooked tomato products, such as tomato sauce; heating tomatoes in oil enhances the bioavailability of lycopene (15) . An anticarcinogenic role for lycopene in the prostate is biologically plausible for several reasons. In cell-free systems, lycopene is more efficient at quenching singlet oxygen and scavenging free radicals than any other commonly consumed carotenoid and ranks higher than other carotenoids tested in prevention of singlet-oxygen induced damage in cultured human lymphoid cells (16, 17, 18) . Oxidative damage, either to DNA or membranes, might play a role in the development of prostate and other cancers (19 , 20) . However, carotenoids and lycopene in particular have biological effects apart from antioxidant activity that could be relevant. In cultured cells, these effects include an increase in intercellular communication via gap junctions (21) , increased differentiation (22) , and altered phosphorylation of regulatory proteins (23) . Whatever the mechanism, it is apparent that lycopene is capable of suppressing the growth of human cancer cells in vitro and of inhibiting both spontaneous and induced tumor development in animal models. Levy et al. (24) reported that lycopene was far more efficient than either {alpha}- or ß-carotene at inhibiting both the basal and insulin-like growth factor type I-induced proliferation of human endometrial, breast, and lung cancer cell lines. Lycopene significantly reduced the occurrence of spontaneous mammary tumors in mice fed a lycopene-enriched diet (25) and, in contrast to ß-carotene, reduced mammary tumor formation in DMBA-treated mice when it was injected i.p. (26) . [...] Our results are consistent with a strong prior hypothesis regarding lycopene and agree closely with our earlier findings, but nevertheless, we believe these results should be interpreted cautiously. Chance cannot be eliminated as an explanation, nor can any observational study demonstrate that lycopene itself, rather than some other compound or factor related to tomato consumption, is responsible for a reduction in prostate cancer risk. Apart from the need for confirmatory epidemiological analyses, many questions regarding the link between lycopene and prostate cancer remain ripe for investigation. The absorption and bioavailability of lycopene appear to be complex processes involving food processing, concurrent dietary lipid intake, cooking method, and, perhaps, levels of lipoproteins (50) . Therefore, the relation of diet to blood levels has not been clarified, nor has the relation of blood levels to those in the prostate itself. The presence of both cis and trans isomers of lycopene in the prostate has been established, but the biological significance of the various isomers is still unknown (28) . If our findings are confirmed in other observational studies, randomized trials should be considered. Meanwhile, these results provide new evidence that increased consumption of tomato products, as part of a diet generally rich in fruits and vegetables, might reduce prostate cancer risk." Giovannucci E. Tomato products, lycopene, and prostate cancer: a review of the epidemiological literature. J Nutr. 2005 Aug;135(8):2030S-1S. Review. PMID: 16046732 [PubMed - indexed for MEDLINE] <http://jn.nutrition.org/cgi/content/full/135/8/2030S> Gann PH, Khachik F. Tomatoes or lycopene versus prostate cancer: is evolution anti-reductionist? J Natl Cancer Inst. 2003 Nov 5;95(21):1563-5. PMID: 14600081 [PubMed - indexed for MEDLINE] <http://jnci.oxfordjournals.org/cgi/content/full/95/21/1563> SignatureMatti Narkia Thanks for posting the abstract, Matti. I wonder if they controlled for the subject's family history. I continue to think that the effect of family history is significant, in that men who know that they are at a higher risk for PCa might consume additional tomato products and other things to try to prevent the disease. So you have a higher risk group already present in the tomato-consuming group. Family history would be easy enough to control for, too -- just ask, and make it a part of the analysis. --charlie > Thanks for posting the abstract, Matti. > [quoted text clipped - 9 lines] > > --charlie What a brilliant bit of analysis, Charlie! I think these kinds of issues are missed all the time. Is there a way to find out the answer to your question? My bet is that you're right on the money. I have hereditary pc (paternal grandfather, father, & older brother got it before me) and I've been consuming LOTS of lycopene (mostly processed tomato products) for years. Gary Thank you, Gary, but this sort of reasoning is pretty well-known among statistical folks, and I emphasize it in every stats course I teach. I wrote more at length about it in a couple of recent threads about excessive vitamin use potentially linked to an increase risk of death in advanced PCa. Others have, too; Prof. Evens, in particular, has discussed this idea several times on this NG. ANd I think that in one of the NCI press releases about the vitamin stuff, they specifically mention that family history may be a significant hidden variable here. The main point of the reasoning tis this: any association, by itself, never implies a causal link, and cannot possibly imply a causal link. When one hears that two things are associated, the first thing one should consider is whether there might be a hidden variable at work in both. Here are two examples that I use in my courses to illustrate the point: 1) Liquor sales and schoolteacher salaries are positively associated in communities accross the country, but parents would be silly were they to conclude that they should lower teachers' salaries since they just blow it all on booze. Of course the hidden variable is the tax base in those communities; a city with a higher tax base can pay its teachers better and its wealthier citizens can afford more liquor. 2) Number of TVs per capita and chilhood mortality rates are negatively associated in countries worldwide, but it would be laughably foolish to ship TVs to the Niger to cure their high childhood mortality rate (284-320 childhood deaths per 1000 live births). It would be funnier if it wasn't one of the most depressing stats I've heard. The hidden variable here is no doubt some sort of longer-term socio-economic variable. A wealthier and more stable country can afford the sanitation facilities that dramatically lower childhood mortality rates. In my stats calsses, I tell my students that if they remember nothing else from the course, to remember this: association does not imply causation. A causal link requires a mechanism. --charlie the next thing they will tell us is that there is no santa claus..... ~ curtis knowledge is power - growing old is mandatory - growing wise is optional "Many more men die with prostate cancer than of it. Growing old is invariably fatal. Prostate cancer is only sometimes so." http://community.webtv.net/PALMER_ENT/doc > the next thing they will tell us is that there is no santa claus..... This is unbearable. I think I'll go out and order a cheeseburger and a beer. And oh yes, hold the ketchup. Alan Somewhere there is, or will be, a study that will indicate just about anything. My thinking is to eat a reasonably healthy and balanced diet and enjoy the beer with it! (wine and whiskey, too!) >> the next thing they will tell us is that there is no santa claus..... > [quoted text clipped - 4 lines] > > Alan I'm wondering about the multi-vitamin I "was" taking that includes 15,000 IUs of Vitamin A as Beta-Carotene? I think the "stress" of taking this multi will completely offset any benifits I may have gleaned. WSF >I'm wondering about the multi-vitamin I "was" taking that includes >15,000 IUs of Vitamin A as Beta-Carotene? I think the "stress" of >taking this multi will completely offset any benifits I may have >gleaned. It seems likely that in beta-carotene in multivitamin tablets is synthetic, because it is cheaper than the natural one. The synthetic beta-carotene's isomer profile is dfferent from natural one's, so their effects are different. In a large alpha-tocopherol- beta-carotene trial in Finland sponsored by NCI of USA and Finnish National Institute of Health synthetic beta-carote was found harmful for smoking males, who were the investigated group and the only participants in this trial. I don't think that synthetic beta-carotene has ever been found beneficial in any study. Natural beta-carotene taken as supplement may not be much better either, it has been speculated that it may disturb the natural balance of dietary carotenoids. I don't take any carotenoids as supplements, but if one wishes to take them, it could possibly be safer to take _natural_ carotenoids as a mixture, where the ratios between individual carotenoids are close to their ratios in a regular healthy diet. SignatureMatti Narkia It sure seems to me that many people are worrying a lot about disputed nuances and all but ignoring the only two regimens I can think of proven to extend our lives and improve our QOL: Mediterranean diet and lots of exercise. That even applies to many people whose PC has already returned after initial treatment. I.P. |
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