A database of blood group correlations to common diseases

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Cancer, Colon

Description:Risk factors for colon cancer include a high meat diet and corresponding low intake of fresh fruits and vegetables. As we will see, having either blood type A or AB should also be considered an important risk factor for colorectal as well.

Cancer cells often manufacture antigens that are typically made only in fetal development and repressed throughout adult life. The opposite of this is also true. That is, when a cell starts to lose genetic control over itself, it can also lose the ability to manufacture antigens which are made when that same cells is healthy.

Earlier, we learned that they amount of blood type antigen made in the colon is highest in the upper colon, the cecum, and diminishes gradually so as to virtually disappear by the very end of the colon, the recto-sigmoid. In colon cancer, the exact opposite happens! The cells of the upper colon lose the ability to produce ABO antigens, while the cells of lower colon start to manufacture them. (2) Since the production of surface antigens is intimately linked with the process of each cell attaching to its neighbor, it is likely that the addition or deletion of blood type antigens from the surface of colon cancer cells is somehow related to their ability to spread, or metastasize. (4) It has even been reported that colo-rectal cancer cells can manufacture blood type antigens of a different blood group than their host. The production of B antigen in normally type A or O individuals with colon cancer has been most often reported. As a matter of fact, in one case the detection of an unwarranted B antigen led to the diagnosis of a previously unknown tumor. (5)

A quick look at the dietary recommendations for type A shows that it fulfills all the nutritional requirements for a lifestyle tailored to reduce the risk of colon cancer. As we have seen, type A possesses none of the abilities to digest dense animal proteins, such as can be found in type O. Indeed the combination of type A's risk for colon cancer and the adoption of a diet high in meat products is a certain recipe for disaster.

Physicians often monitor a tumor marker called the CEA, or 'carcino-embryonic antigen' when gauging the progression of colon cancer. Like most tumor markers, the CEA is a glycoprotein, the same class of molecule as blood type antigens. It appears that expression of blood type A antigen is intimately related to synthesis of CEA.

In 1987 researchers looked at the expression of blood group antigens in relation to the production of CEA in human colon carcinoma cells of different ABO blood types. All tumor cells made A and B antigens regardless of the patients' original blood type. However, tumor cells from O type patients had lower expression of both A and B antigens and high production of CEA. Cells from patients with A type blood had low to undetectable CEA production and high expression of both A and B antigens. (6) I have verified this in my own practice, where it does seem that colon cancer patients of type O blood manufacture many more times the amount of CEA than type A.

In 1995 an article published in the Journal of Cell Biochemistry reported that ˘Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells.÷

Certain chemically-induced rat colon tumors display many features of human cancer, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. Using antibodies developed to chemically induced tumors of the colon, the researchers found that these same antibodies reacted the epitope (binding site) also expressed in blood group A human colon carcinoma cell lines but not in cell lines whose donors were type B. The researchers offered that ˘blood group A-specific lectins may provide a useful tool for early detection of colon cancer.÷ (9)

Interestingly, the type A antigen made by cancer cells in the lower colon are embryonic variations not seen typically in adults. In one study four variants of the type A antigen were found in human colon cancer cells, but of these only one was found in adults, the other three are variants of type A typically only found in fetal tissue. (11) I find this fascinating because, as you may remember, one of the primary roles blood type antigens play in the developing fetus involves shaping the architecture of developing tissue and organs, by serving as cell-to-cell attachment and detachment points. The question is: Does the re-development of these 'fetal' forms of type A permit tumor cells to develop the ability to detach from the primary site and spread through the body?

There is a strange but documented link between the expression of blood group antigens in tumors of the thyroid and lower colon. (11) Thus type As who have had a history of thyroid tumors, either benign or malignant, may want to consider themselves at especially high risk of developing cancer of the lower colon.
Thomsen-Friedenreich, again.

As we have seen in our discussion of stomach and breast cancer, this tumor marker is often expressed in malignancy, and is important to our topic because it has been shown that immunologically, the Thomsen-Friedenreich antigen (usually called 'Tn antigen') bears some resemblance to the type A antigen, which can potentially derail the immune response to certain tumors in people of this blood type. For example, it has been shown that type A blood is associated with lower levels of naturally occurring antibodies to this tumor antigen. (45) 'Tn' antigen is a 'pancarcinoma antigen' found in many different cancers. It is often expressed by colon cancer cells, and the degree of its elaboration is a pretty good index of the tumor's aggressiveness. In addition to colon cancer, Tn is also expressed in ulcerative colitis (171) which may help explain why chronic ulcerative colitis is a risk factor for the subsequent development of colon cancer.

Thus we have three strikes immunologically against type A (and probably AB) with regard to colon cancer:

+ The Tn tumor antigen is to a degree seen as 'self' by type A, which accounts for the lower amounts of anti-Tn.The CEA or carcino-embryonic antigen, a common tumor marker of malignancy often elevated in colon cancer, is structually related to the blood type A antigen.Colon cancer cells of the recto-sigmoid area, the area which most often develops colon cancer, manufacture large amounts of type A antigen, (165, 167) even in people who are not type A. Also, the amount of type A antigen made seems to correlate with the potential for metastasis, or spread.
References:1. Freed DL, et al Letter: Do dietary lectins protect against colonic cancer? Lancet. 1975 Dec 20;2(7947):1261-2.

2. Cooper HS, Marshall C, Ruggerio F, Steplewski Z Hyperplastic polyps of the colon and rectum. An immunohistochemical study with monoclonal antibodies against blood groups antigens (sialosyl-Lea, Leb, Lex, Ley, A, B, H). Lab Invest 1987 Oct;57(4):421-8

3. Salem RR, Wolf BC, Sears HF, Lavin PT, Ravikumar TS, DeCoste D, D'Emilia JC, Herlyn M, Schlom J, Gottlieb LS, et al Expression of colorectal carcinoma-associated antigens in colonic polyps. J Surg Res 1993 Sep;55(3):249-55

4. Blottiere HM, Burg C, Zennadi R, Perrin P, Blanchardie P, Bara J, Meflah K, Le Pendu J Involvement of histo-blood-group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity Int J Cancer 1992 Oct 21;52(4):609-18

5. Northoff H, Wolpl A, Bewersdorf H, Faulhaber JD An ABO-blood group abnormality leading to the detection of a colon-carcinoma. Blut 1983 Mar;46(3):161-4

6. Schoentag R, Primus FJ, Kuhns W. ABH and Lewis blood group expression in colorectal carcinoma. Cancer Res 1987 Mar 15;47(6):1695-700

7.Kawaguchi T [Adhesion molecules and carbohydrates in cancer metastasis]. Rinsho Byori 1996 Dec;44(12):1138-46

8.Slater G, et al Clinicopathologic correlations of ABO and Rhesus blood type in colorectal cancer. Dis Colon Rectum. 1993 Jan;36(1):5-7.

9.Laferte S, Prokopishyn NL, Moyana T, Bird RP Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and human colon cancer cell lines Cancer J Cell Biochem 1995 Jan;57(1):101-119

10. Vowden P, et al Thyroid blood group isoantigen expression: a parallel with ABH isoantigen expression in the distal colon. Br J Cancer. 1986 Jun;53(6):721-5.

11. Itzkowitz SH Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms. J Cell Biochem Suppl 1992;16G:97-101

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2014-4-24: Current Date 2:32:18 GMT: Current Time

PathType is a searchable database of blood group and disease associations, clinical correlates and citations.
By Peter D'Adamo. Copyright 2001-2011.