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http://denvernaturopathic.com/lycopeneandcervicalcancer.htm

Ketchup and Cervical Cancer:
Jacob Schor ND, FABNO
June 6, 2010

An interesting study was published earlier this year that has me encouraging our daughter to eat more ketchup on her food.

The study was on cervical cancer and looked at the risk of being diagnosed with this type of cancer and how it related to diet, particularly at several micronutrients in the diet. Cervical cancer is relatively rare in the United States; about 11,270 cases were diagnosed in the US in 2009 and was responsible for 4,070 deaths.

Internationally the situation is quite different. “Cervical cancer is the third most common cancer worldwide, and 80% of cases occur in the developing world. It is the leading cause of death from cancer among women in developing countries, where it causes about 190,000 deaths each year.”

Part of the difference of course is preventive screening. PAP smears that look for early signs of cervical cancer have been widely adopted in the United States. Early detection and early treatment of cervical cancer works well in countries that can afford it. But what about countries that can’t afford these modern interventions. It appears from this recent study that simply eating better can reduce risk significantly. And of all things, ketchup.

We had better back up a bit and fill in the details. The study I’m referring to was published last February in the International Journal of Cancer and written by Tomita et al, team members of the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (BRINCA) Study Team. They looked for an association between levels of various carotenes and tocopherols in the blood serum of patients with cervical cancer. Data was collected from 605 low income women newly diagnosed with invasive cervical intraepithelial neoplasia (CIN), grades 1, 2, 3 or invasive cancer who were treated at either of two public health clinics in São Paulo, Brazil between 2003 and 2005. The cases were divided into 4 groups by histological diagnosis (CIN1, n = 140; CIN2, n = 126; CIN3, n = 231; invasive cancer, n =108) and 453 controls.

After adjusting for the confounding variables and HPV status, there was a significant inverse relationship between serum lycopene levels and CIN1, CIN2, and cervical cancer when the highest and lowest tertiles of lycopene were compared:

Stage Odds Ratio (95% CI)
CIN1 0.53 (0.27-1.00, p for trend = 0.05)
CIN3 0.48 (0.22-1.04, p for trend = 0.05)
Invasive Cancer 0.18 (0.06-0.52, p for trend = 0.002)

Let me try and explain this in clearer terms. The women were ranked by the concentration of lycopene in their blood. Think of how school students are ranked by cumulative grade point averages. The researchers compared cancer statistics for women who were in the top third of the class, or what they call the upper tertile, against women in the lower third of the ranking. The researchers express the rate of cervical cancer for these two groups as a ratio, what is called an Odds Ratio. Thus for example, the Odds Ratio for developing invasive cervical cancer was 0.18. This ratio can be expressed a number of different ways. One can say that the group of women with the higher levels of lycopene have a rate of cervical cancer that is 82% lower than the other group.

Having greater amounts of lycopene lowered the chance of getting cervical cancer.
High levels of serum alpha- and gamma-tocopherols, and higher consumption of dark green and deep yellow vegetables/fruit were associated with almost 50% decreased risk of CIN3.

We typically assume that cervical cancer is directly caused by infection with human papillomavirus (HPV), but that’s an oversimplification. It is more accurate to say that infection with, “…. HPV is recognized as being a necessary, but not sufficient, cause of cervical cancer.” It is not being infected that is the real problem, it is the persistence of the infection that increases risk. The longer the infection lingers, the more likely that the woman will develop cancer.

Persistence of HPV infection depends on a number of factors; older women clear it faster, poorer women clear it slower. Younger poor women clear it even slower. This sociodemographic variation in risk may be simply a matter of nutritional status. The speed of HPV clearance varies with micronutrient status. If one is nutritionally deficient, the virus lingers longer. Some studies report t a range of chemicals that are important: “…levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time…” But a number of studies others single out particular nutrients, particularly, vitamin A and lycopene, or vitamin E and cryptoxanthin, lycopene may, in this regard, be the most essential micronutrient. The current study certainly does suggest it is.

Seen in this light, the benefit seen in this Tomita study, is in line with past research. The magnitude of the protective benefit is still striking. Risk of CIN 1 and 3 is cut by half. Risk of invasive cancer is cut by more than 80%.

Cooked tomato products are the best source of dietary lycopene. Ketchup, particularly the organic products, can be a significant source of lycopene. Might they also reduce incidence of cervical cancer death?

If a food manufacturer wishes to make a health claim on a food package label, then pre-approval by the FDA is required. The FDA published a review paper in 2007 that stated that there was not sufficient evidence to support a label claim that lycopene has a protective effect against long list of cancers.
The evidence required to support such a claim is quite stringent. “Eighty-one observational studies examined the relationship between lycopene intake and the risk of prostate, lung, colorectal, gastric, breast, cervical, ovarian, endometrial, or pancreatic cancer, all of which FDA excluded from consideration.” The reason given for exclusion was that, “…none was an interventional study of lycopene intake in subjects who had not been diagnosed with cancer.”

The FDA looked at a second sequence of studies and found most were not done to their satisfaction, explaining that, “A total of 64 observational studies of the association between tomato or tomato product consumption and cancer risk were identified.” Of the 64 studies, 23 were discarded because, “[they were a ] reanalysis of data that were already used to evaluate the health claim and/or because they had scientific deficiencies that prevented FDA from drawing scientific conclusions from the study.” From the 39 remaining studies, the FDA was unable to draw firm conclusions. Our readers are encouraged to review the FDA’s reasoning for discounting these studies first hand. http://jnci.oxfordjournals.org/cgi/content/full/99/14/1074


Reading through the material, you will probably find, as I did, that alhough the research may not be strong enough to make label claims, it is more than convincing enough to think, “This won’t hurt and probably will help.”

This information should generate a particular rumination on the part of our readers. The somewhat entertaining thought is whether the relatively low rate of cervical cancer in the United States is really a result of our proactive diagnostic PAP smears or simply the fact that young women at high risk for HPV infection consume a great deal of ketchup.

Related Newsletters from the past:

Tomatoes: the redder the better:
http://denvernaturopathic.com/news/lycopene.html

Why buy organic ketchup?
http://denvernaturopathic.com/organic.htm

Referenced version of this article with abstracts is posted at:
http://denvernaturopathic.com/lycopeneandcervicalcancer.htm

References:

Int J Cancer. 2010 Feb 1;126(3):703-14.
Diet and serum micronutrients in relation to cervical neoplasia and cancer among low-income Brazilian women.
Tomita LY, Longatto Filho A, Costa MC, Andreoli MA, Villa LL, Franco EL, Cardoso MA; Brazilian Investigation into Nutrition and Cervical Cancer Prevention (BRINCA) Study Team.
Department of Nutrition, School of Public Health, University of São Paulo (USP), São Paulo, SP, Brazil.
Abstract
Cervical cancer is a leading cancer among women in developing countries. Infection with oncogenic human papillomavirus (HPV) types has been recognized as a necessary cause of this disease. Serum carotenoids and tocopherols have also been associated with risk for cervical neoplasia, but results from previous studies were not consistent. We evaluated the association of serum total carotene and tocopherols, and dietary intakes with the risk of newly diagnosed, histologically confirmed cervical intraepithelial neoplasia (CIN) grades 1, 2, 3 and invasive cancer in a hospital-based case-control study in São Paulo, Brazil. The investigation included 453 controls and 4 groups of cases (CIN1, n = 140; CIN2, n = 126; CIN3, n = 231; invasive cancer, n =108) recruited from two major public clinics between 2003 and 2005. Increasing concentrations of serum lycopene were negatively associated with CIN1, CIN3 and cancer, with odds ratios (OR) (95% CI) for the highest compared to the lowest tertile of 0.53 (0.27-1.00, p for trend = 0.05), 0.48 (0.22-1.04, p for trend = 0.05) and 0.18 (0.06-0.52, p for trend = 0.002), respectively, after adjusting for confounding variables and HPV status. Increasing concentrations of serum alpha- and gamma-tocopherols, and higher dietary intakes of dark green and deep yellow vegetables/fruit were associated with nearly 50% decreased risk of CIN3. These results support the evidence that a healthy and balanced diet leading to provide high serum levels of antioxidants may reduce cervical neoplasia risk in low-income women.
PMID: 19642096 [PubMed - indexed for MEDLINE]

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