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PETER J. D'ADAMO, ND
WHAT IS CANCER?
Cancer: the mere mention of its name generally is enough to warrant concern or trepidation. Cancer is not a new disease and it is not restricted to only a few countries. At one point in the 1970's, the U.S. declared a war on cancer. It is a war where to date we have lost most of the battles. In fact, although the risk of a few types of cancer has declined dramatically in developed countries in this century, the incidence of the most significant forms of the disease has increased. Breast cancer, prostate cancer, colon cancer, rectal cancer, and lung cancer are among the cancers that have become more common. Researchers have suggested that many factors under our control such as cigarette smoking, unhealthful dietary habits and exposure to chemicals might be partially to blame for the increase in cancer. Many of our modern conveniences from drugs to cellular telephones have also received media attention for possible links to cancer. In fact, epidemiologists have suggested that in maybe as many as ¾ of all cancers, the environment (including lifestyle factors) might play a profound role.
Cancer is a general term for a group of over 100 diseases characterized by the uncontrolled growth and spread of abnormal cells. All organs of the body are made up of cells capable of normal division to produce more cells when the body needs them. If cells divide when new ones aren't needed, they form a mass of excess tissue called a tumor. Tumors can be benign (non-cancerous) or malignant (cancerous).
The cells in malignant tumors can invade and damage nearby tissues and organs. Cancer cells can also break away from a malignant tumor and travel through the bloodstream or the lymphatic system to form new tumors in other parts of the body. The spread of cancer is called metastasis.
As with many other diseases, both genetic and environmental factors are implicated in the cause and development of human cancers. Cancer-causing biological, chemical, and physical agents are referred to as 'carcinogens' and the process of a carcinogen instigating cancer is called 'carcinogenesis.' Recent advances in the molecular biology of cancer, stemming from the study of cancer-causing viruses ('oncoviruses')and transforming DNA, are providing new ways of investigating cancer-forming genes ('oncogenes') and cellular pathways which are involved in the mechanisms of viral, chemical, and physical carcinogenesis.
Carcinogens are grouped into two categories, Direct-acting carcinogens, those which are carcinogenic on their own, and 'procarcinogens,' those that must be converted metabolically inside the body into carcinogens. Paradoxically, most forms of chemotherapy for cancer are direct acting carcinogens as well. Procarcinogens include aflatoxin (the toxin from mold), many chemical dyes, nitrosamines from smoked foods in the diet and some metals, such as nickel. Carcinogenesis can take years or decades to finally result in a tumor. This latent period between an exposure to a carcinogen and cancer formation is explained by studies showing that carcinogenesis is divisible into two stages, tumor initiation and promotion.
INITIATORS AND PROMOTERS
The general feeling about carcinogenesis is that it is a two-step process, an initial exposure, and a subsequent stimulation by some sort of 'promoter.' Following exposure to a subcarcinogenic dose of a carcinogen (the 'initiator') the latent period can be shortened and the tumor yield increased by treatment with certain "promoting agents" (such as many hydrocarbons) which are not carcinogenic in themselves (or very weakly so) but cause a lot of cell growth in initiator-stimulated tissue, a process that may be necessary to 'lock in' the effect of the initiator. We think this , because wound healing also has a tumor promoting effect: Wounding of an area of skin treated with a carcinogen brings out tumors along the edge of the wound.
Initiation is caused by chemical, physical, or biological agents which irreversibly alter the cells genetic material. The mechanism of Promotion is not well understood: Promoters trigger cell proliferation, an apparently necessary process in the 'fixation' or expression of tumor initiation.
Many independent factors, such as gender, diet, age and a slew of environmental factors may have a modifying role in increasing, or decreasing, the susceptibility to carcinogens. DNA is able to repair itself. A failure in some aspect of the repair mechanism leads to mutated DNA. Sometimes mutated DNA can remain in the repressed state, which usually means that a cancer will not develop. In essence, as long as there are enough anti-Promoters (such as the antioxidants) the body can repair the damage to the DNA or repress the damage enough to avoid malignancy.
ONCOVIRUSES AND ONCOGENES
Oncoviruses can induce spontaneously arising cancers in animal species as diverse as chickens, cats, cattle and apes. Human T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be isolated and characterized, is considered the causative agent of a relatively rare T-cell lymphoma/leukemia seen mainly in Japan and the Caribbean Islands. Chemical carcinogenesis by tobacco smoke products is a major cause of common lung cancers. Skin carcinogenesis by solar ultraviolet radiation is expected to increase even above its present high incidence as the ozone layer of the atmosphere undergoes depletion. Still, despite the fact that we know quite a bit about carcinogens and carcinogenesis, the specific causes of most common human cancers - of breast, colon, rectum, lymph nodes, uterus, bladder, pancreas, bone marrow, stomach etc. remain largely unknown.
In addition to oncogenes, it is now recognized that mutations or inappropriate activation of several different classes of cellular genes are probably involved in the usual multiple-step process that leads to human cancer. including tumor suppressor genes, DNA nucleotide mismatch repair genes, and genes that mediate programmed cell death, or apoptosis. While the activation of some genes may result in cancer, it is reasonable to suppose that the activation of other genes may suppress the development of cancer. The existence of 'tumor suppressor genes' in normal cells is now well established, and it is possible, therefore, that the loss or inactivation of tumor suppressing genes may remove a block to cell proliferation and the development of the cancer state.
The best known of the tumor suppressing genes is 'p53 which controls several cell functions, including regulation of the cell division cycle, the repair of the cell's DNA, and programmed cell death. Accordingly, p53 has been dubbed the 'guardian of the genome.'
The most common observed trait that oncogenes confer on the affected cells is 'immortalization,' the ability to be propagated in cell culture continuously without limit. If oncogenes are likened to an 'gas pedal' of cell proliferation or transformation and tumor suppressor genes to a 'brake,' then apoptosis is a final 'suicidal crash.'
Most, if not all, of the many proteins encoded by cellular oncogenes are involved in the 'growth factor-receptor-response' pathways of transmission of growth stimulatory signals from the cell surface to the nucleus, culminating in the transcription of certain genes and in DNA synthesis. As we will see, the activity of several of these growth factors are intimately linked to blood type.
Most studies of genes and growth factors involved in carcinogenesis have focused on functions that have a positive stimulatory effect on cell proliferation and, hence, neoplastic transformation.
BLOOD TYPE AND CANCER
Although there are probably over a thousand publications on the associations of blood groups and disease, many are based totally on statistical analyses. Most of the earlier studies have been controversial, because they were small studies and/or had inadequate controls and/or had been analyzed incorrectly. Nevertheless, it is difficult to argue with the general pattern that emerges from the large body of statistical data on malignancy, coagulation and infection. Some of the findings on microbe receptors, and the association with important immune proteins are most convincing and suggest that blood group antigens do play an important biological role: A role that is often completely unrelated to the red blood cell. It can be said at the outset, that cancers in genral tend to be associated with group A, and slightly less strongly with group B. With that, let's look at some trends among selected cancers with regard to blood type.
Breast cancer is the most common cancer among women. And while the mortality rates are falling slightly for some sub-populations of women, it is still a potentially lethal adversary. Standard treatment can vary but procedures such as lumpectomy surgery (removal of the tumor and some surrounding tissue), mastectomy (removal of the whole breast), chemotherapy, radiation, and hormone-blocking therapy are the norm with any combination of the above strategies potentially employed. Mammograms have been a major push within medicine as a means of early detection; however, many of my patients have actually discovered there tumors on self-examination of breast tissue, so I cannot overemphasize this self-help procedure (especially for A's and AB's as we will see). While many risk factors are associated with the development of breast cancer, it is seldom mentioned that blood type has an influence on susceptibility and outcomes. In fact, some researchers have even gone so far as to say that "blood groups were shown to possess a predictive value independent of other known prognostic factors" when discussing breast cancer. Other researchers have actually suggested that a degree of the susceptibility to breast cancer, from a gene perspective, might be a result of a breast cancer-susceptibility locus linked to the ABO locus located on band q34 of chromosome 9.
Costantini M, Fassio T, Canobbio L, et al. Role of blood groups as prognostic factors in primary breast cancer. Oncology 1990;47(4):308-12
Skolnick MH, Thompson EA, Bishop DT, Cannon LA. Possible linkage of a breast cancer-susceptibility locus to the ABO locus: sensitivity of LOD scores to a single new recombinant observation. Genet Epidemiol 1984;1(4):363-73
My observation has been that blood type A women have a generalized tendency to worse outcomes and a more rapid progression with this cancer. Research indicates that blood type A women are over-represented among breast cancer patients, and that this trend occurs even among women thought to be at low risk for cancer. One of the most significant risk factors for a rapidly progressing breast cancer is also blood type A, and blood type A women have been observed to have poorer outcomes once they are diagnosed with breast cancer. In complete opposition to these blood type A tendencies, we find blood typee O. Blood type O infers a slight degree of resistance against breast cancer, and even among patients, blood type 0 showed a significantly lower risk of death. Type AB's fall nearer to A's, having a slight increase in susceptibility and a more dramatic trend towards recurrence and shorter survival times. Blood type B generally acts a bit more like blood type O, imparting a degree of reduced susceptibility or reduced risk. This is particularly evident among women who do not have a family history of breast cancer. However, there are two areas to consider if you are a blood type B woman. If you have had a family member with breast cancer, the protection normally associated with being a B women goes out the window, and you need to be more aware of the possibility of breast cancer. Also, if you are a B women and currently have or have had breast cancer, statistically speaking, your odds of a recurrence of breast cancer tend to be higher. Part of the reason for this is that you tend to survive the original cancer, but nevertheless, you might want to consider some of the long-term immune building and anti-cancer strategies we will discuss.
Mourali N, Muenz LR, Tabbane F, et al. Epidemiologic features of rapidly progressing breast cancer in Tunisia. Cancer 1980;46:2741-6
Rosen PP, Schwartz MK, Menedez-Botet CJ. Blood groups and response to therapy for mammary cancer. Am J Clin Pathol 1977;67:504-5 [Letter]
Anderson DE, Haas C. Blood type A and familial breast cancer. Cancer 1984 Nov
Costantini M, Fassio T, Canobbio L, et al. Role of blood groups as prognostic factors in primary breast cancer. Oncology 1990;47(4):308-12
Tryggvadottir L, Tulinius H, Robertson JM. Familial and sporadic breast cancer cases in Iceland: a comparison related to ABO blood groups and risk of bilateral breast cancer. Int J Cancer 1988 Oct 15;42(4):499-501
Horn PL, Thompson WD. Risk of contralateral breast cancer. Associations with histological, clinical, and therapeutic factors. Cancer 1988;62:412-24.
Holdsworth PJ, Thorogood J, Benson EA, Clayden AD. Blood group as a prognostic indicator in breast cancer. Br Med J (Clin Res Ed) 1985 Mar 2;290(6469):671-3
Breast cancer shows a weaker association with being a non-secretor.
FEMALE REPRODUCTIVE CANCERS (GYNECOLOGICAL TUMORS)
As a general rule, gynecological tumors occur more frequently and are associated with worse prognosis in blood type A women. As examples, endometrial cancer occurs more frequently in Type A, ovarian cancer occurs more frequently in A's and AB's. For both of these cancers blood type A is associated with worse 5- and 10-year survival. Conversely, the best survival rate is seen among blood type O women, followed by B women. Type B women are also the least likely to have an ovarian tumor that is malignant. With regard to cervical cancer, analysis also shows a strong trend towards higher frequency of cancer and poor outcomes among A women, a slight trend towards increased risk for B's, and a better 5-year survival among 0 blood phenotype.
Marinaccio M, Traversa A, Carioggia E, et al. Blood groups of the ABO system and survival rate in gynecologic tumors. Minerva Ginecol 1995 Mar;47(3):69-76
Bjarnason O, Tulinius H. Tumours in Iceland. 9. Malignant tumours of the ovary. A histological classification, epidemiological considerations and survival. Acta Pathol Microbiol Immunol Scand [A] 1987 Jul;95(4):185-192
Nayak SK. ABO blood groups in different diseases. J. Ind Med 19971;87:449-52
Rybalka AN, Andreeva PV, Tikhonenko LF, Koval'chuk NA. ABO system blood groups and the rhesus factor in tumors and tumorlike processes of the ovaries. Vopr Onkol 1979;25(3):28-30 [Article in Russian]
Mori M, Kiyosawa H, Miyake H. Case-control study of ovarian cancer in Japan. Cancer 1984 Jun 15;53(12):2746-52
Langer M, Gitsch E, Salzer H. Significance of ovulatory age in the pathogenesis of ovarian cancer. Geburtshilfe Frauenheilkd 1984 Jun;44(6):366-7
Kaur I, Singh IP, Bhasin MK. Blood groups in relation to carcinoma of cervix uteri. Hum Hered 1992;42(5):324-6
* Type O associated with better 5-year survival for cervical cancer.
* Type O associated with better 5- and 10-year survival for endometrial cancer.
* Type O and B associated with better 5-year survival for ovarian cancer.
Similar to other cancers we will mention, ovarian cancer is characterized by a loss of blood type antigens. Uterine endometrial cancers often have an opposite presentation. Normal endometrial tissue does not contain ABO antigens; however, over ½ of endometrial cancers have detectable A, B or H antigens. An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, is also observed in endometrial cancers compared with its expression in normal endometria.
Metoki R, Kakudo K, Tsuji Y, et al. Deletion of histo-blood group A and B antigens and expression of incompatible A antigen in ovarian cancer. J Natl Cancer Inst 1989 Aug 2;81(15):1151-7
Tsukazaki K, Sakayori M, Arai H, et al. Abnormal expression of blood group-related antigens in uterine endometrial cancers. Jpn J Cancer Res 1991 Aug;82(8):934-41
Bladder cancer appears to be an exception to the generalized observation of A's and cancer aggressiveness. In a study by Llopis et al, the researchers noticed that blood group O had a tendency to increased aggressiveness, higher tumor grade, and more relapses. Surprisingly, blood type A individuals generally were less likely to have aggressive cancer and were somewhat protected against relapses of bladder cancer. Srinivas et al observed a similar trend. They found that among 141 patients with bladder cancer, individuals with blood group A had lower grade tumors and lower mortality rates. Blood type O's generally had higher grade tumors and higher mortality rates. Other researchers have also observed similar trends, such as the blood type O tendency to higher grade tumors, larger tumors, progression to advanced disease, and increased rates of mortality (especially after 8 years).
Llopis B, Ruiz JL, Server G, et al. ABO blood groups and bladder carcinoma. Eur Urol 1990;17(4):289-92
Srinivas V, Khan SA, Hoisington S, Varma A, Gonder MJ. Relationship of blood groups and bladder cancer. J Urol 1986 Jan;135(1):50-2
Orihuela E, Shahon RS. Influence of blood group type on the natural history of superficial bladder cancer. J Urol 1987 Oct;138(4):758-9
Raitanen MP, Tammela TL. Relationship between blood groups and tumour grade, number, size, stage, recurrence and survival in patients with transitional cell carcinoma of the bladder. Scand J Urol Nephrol 1993;27(3):343-7
Similar to most cancers, bladder cancer is characterized by a dissappearance of normal ABO antigen expression and an appearance of specialized adherence molecules.
Orlow I, Lacombe L, Pellicer I, et al. Genotypic and phenotypic characterization of the histoblood group ABO(H) in primary bladder tumors. Int J Cancer 1998 Mar 16;75(6):819-24
Orntoft TF, Wolf H. Molecular alterations in bladder cancer. Urol Res 1998;26(4):223-33
Blood Type O is associated with higher grade, larger, more aggressive bladder cancer. They tend to have the greatest tendency to advanced disease, more relapses, and higher mortality rates. Blood type A is actually protective for this type of cancer. Blood type AB inherits the A tendency for protection, while blood type B's fall closer to O with regard to this cancer.
Lung Cancer is and has been one of the leading causes of cancer deaths in the U.S. It is expected that about 180,000 new cases will be diagnosed within the U.S. this year, and of these, about 160,000 people will die. While the incidence of lung cancer has been declining in men since the 1980s, it is still rising in women. The most well known risk factor for lung cancer is cigarette smoking (which has been linked to 85 to 90 percent of all cases). Other well known risk factors include exposure in the workplace to certain substances (including asbestos and some organic chemicals), radiation exposure, radon exposure (especially in smokers), and even second-hand environmental tobacco smoke.
Because of the close associated of lung cancer with cigarette smoking, we would expect this strong risk factor to possibly overwhelm any blood type differences. However, we still see a higher number of A's and a lower number of O's with lung cancer. This trend is even greater among individuals younger than 50 (where it is especially high). This suggests that smoking, which increases risk for lung cancer with each decade of exposure, somewhat mutes the blood type connection in a population which has had many decades of smoking history, but still cannot camoflage the blood type A connection to lung cancer.
Roots I, Drakoulis N, Ploch M, et al. Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk. Klin Wochenschr 1988;66 Suppl 11:87-97
Evidence also suggests that loss of blood group A antigen on lung tumor tissue is a strong adverse prognostic marker for patients with resected non-small cell lung cancer (NSCLC).
Graziano SL, Tatum AH, Gonchoroff NJ, Newman NB, Kohman LJ. Blood group antigen A and flow cytometric analysis in resected early-stage non-small cell lung cancer. Clin Cancer Res 1997 Jan;3(1):87-93
DIGESTIVE SYSTEM CANCERS:
It has been consistently observed that blood type A is associated with an increased risk for stomach cancer and poorer survival. Blood type O on the other hand, appears to exert a protective effect by preventing the growth and spread of the tumor and being associated with longer survival times.
Because of this strong relationship between stomach cancer and blood type A, some researchers have hypothesized gastric cells produce an antigen immunologically related to blood group A. This appears to be the case to a degree, with stomach cancer cells expressing the A-like Thompsen-Friedenreich (T) antigen. Blood type A individuals, have a tendency to a lower natural anti-Thompsen-Friedenreich immune response. This tendency is quite strong in A's with stomach cancer, who of all blood groups demonstrate the greatest and uniform suppression of the level of TFA agglutinins, irrespective of age, cancer stage or tumor morphology.
Stomach cancer is also often characterized by exuberant secretion of type A antigens. This characteristic is not limited to those who are type A blood. Large amounts of A antigen have also been observed in the less common tumors of types B and O. It appears that the progression of stomach cells to stomach cancer involves a necessary mutation at the ABO gene, the result of which is the production of A antigen, even if this is not the person's blood type. Of course having a blood type such as O or B and capable of attacking A-like things, such as cancer cells, gives these blood types a considerable advantage. Conversely, it appears that stomach and intestinal pre-cancerous and cancer cells tend to lose the H and B antigens, making immune detection in these blood types more likely. (46)
The presence of p53 mutations is associated with stomach cancer and with blood type A. Because glucocorticoid receptors are found in high numbers on stomach cancer cells, high stress hormone levels (the blood type A achilles heal) might also contribute to poor outcomes in individuals with stomach cancer.
Nayak SK. ABO blood groups in different diseases. J. Ind Med 19971;87:449-52 Klechova L, Gosheva-Antonova Ts. ABO and Rh blood group factors in thyroid gland diseases. Vutr Boles 1980;19(4):75-9 [Article in Bulgarian]
Csato E, Vass J. Frequency of non-secretor types among stomach cancer patients. Haematologia (Budap) 1986;19(2):147-50
Beckman L, Angqvist KA. On the mechanism behind the association between ABO blood groups and gastric carcinoma. Hum Hered 1987;37(3):140-3
Kurtenkov O, Klaamas K, Miljukhina L. The lower level of natural anti-Thomsen-Friedenreich antigen (TFA) agglutinins in sera of patients with gastric cancer related to ABO(H) blood-group phenotype. Int J Cancer 1995 Mar 16;60(6):781-5
Palli D, Caporaso NE, Shiao YH, et al. Diet, Helicobacter pylori, and p53 mutations in gastric cancer: a molecular epidemiology study in Italy. Cancer Epidemiol Biomarkers Prev 1997 Dec;6(12):1065-1069
Falling into the category of the slightly mysterious, being a non-secretor is associated with a slight decrease in the prevalence of stomach cancer.
Csato E, Vass J. Frequency of non-secretor types among stomach cancer patients. Haematologia
DIGESTIVE SYSTEM CANCERS:
PANCREATIC CANCER, LIVER CANCER, & GALL BLADDER CANCER
Pancreatic cancer carries an increase in risk for both blood types A (RR 1.52) and B (1.5), while blood type O confers a degree of protection.
Similar to several other types of cancer, blood type antigenic structures on pancreatic cancerous cells are quite prevalent and are capable of changing. There is also a capability for inappropriate expression of blood type antigens with pancreatic cancer. In all reported cases, this has been manifested by either an A or an O individual expressing B antigens on the pancreatic cancer. Perhaps this is indicative of a B-like nature to this cancer (at least in some individuals) and partly explains the increase in risk for B's.
Vioque J, Walker AM. Pancreatic cancer and ABO blood types: a study of cases and controls. Med Clin (Barc) 1991 May 25;96(20):761-4 [Article in Spanish]
Annese V, Minervini M, Gabbrielli A, Gambassi G, Manna R. ABO blood groups and cancer of the pancreas. Int J Pancreatol 1990 Mar;6(2):81-8
Uchida E, Tempero MA, Burnett DA, Steplewski Z, Pour PM. Correlative studies on antigenicity of pancreatic cancer and blood group types. Cancer Detect Prev Suppl 1987;1:145-8
Cancers of the liver show a slight association with blood type A. Cancers of the gall-bladder and bile ducts show a strong association with blood type A and B.
DIGESTIVE SYSTEM CANCERS:
Colorectal cancer is among the most frequent cancers in the United States, with an estimated 133,000 new cases predicted (94,000 for colon and 39,000 for rectum). About 55,000 deaths from colorectal cancer are expected this year.
Some of the most common risk factors include a family history of colorectal cancer; polyps or inflammatory bowel disease. Other risk factors can include physical inactivity, exposure to certain chemicals and a high-fat or low-fiber diet.
Colon cancer is actually one of the relatively few diseases with a significant association to an individual's Rh blood type. Although Rh+ and Rh- individuals are about equally likely to have colon cancer, Rh- individuals are more likely to have a localized disease, while Rh+ individuals are more likely to have metastatic disease. This suggests that Rh+ patients with colorectal cancer are less protected against tumour spread than Rh- patients, especially with regard to regional lymph node metastases.
Halvorsen TB. ABO blood groups, rhesus types, and colorectal adenocarcinoma. A retrospective study of 747 cases. Scand J Gastroenterol 1986 Oct;21(8):979-83
Early studies showed an association of cancers of the large intestine with blood type A. However, this association is weaker than that found with stomach cancer. Perhaps the largest link to blood type and colon cancer is found with respect to the appearance or dissappearance of blood type antigens. It is commonly recognized that altered blood group antigen expression is a hallmark of malignancy in this form of cancer. During the progression to malignancy of colonic cancer cells, the blood group antigens A, B, H, and Le(b), which are normally expressed only in the proximal colon, can be re-expressed in distal colon cancers or deleted in proximal colon cancers. An individual can also actually even express an antigen which is incompatible with the individual's blood type (so a blood type B could express an A antigen).
Itzkowitz SH. Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms. J Cell Biochem Suppl 1992;16G:97-101
Because of this phenomenon, of colon cancer cells altering of the surface structure, some researchers have suggested that specific lectins (such as amaranth lectin) might provide a useful tool for early detection of colon cancer (in fact they might also be potentially useful therapeutically as well). The lectins that have been discussed to date have been specific for blood type A. This is in order to take advantage of the changed structural glycoconjugates which tend to have a more A-like alteration (though this would be to an extent influenced by primary ABO type, secretor status, and Lewis phenotype).
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 azomethane-induced rat colon tumors and human cancer cell lines. J Cell Biochem 1995;57:101-19.
Vicia faba agglutinin, the dietary lectin found in broad beans (fava beans) has also been suggested as a possibility to slow the progression of colon cancer. Basically, it appears that Vicia faba agglutinin can stimulate an undifferentiated colon cancer cell line to differentiate into glandlike structures. In other words, this lectin can make malignant colon cancer cells transform back to morphologically healthy, purposeful cells. We will discuss how important differentiation is to cells, and that cancer cells are characterized by a loss of differentiation. The same researchers also found that this lectin as well as the lectin in the common edible mushroom, inhibit proliferation of colon cancer cell lines.
Jordinson M, et al. Gut 1999;44:709-714.
DIGESTIVE SYSTEM CANCERS:
ORAL CAVITY AND ESOPHAGUS
Cancer of the lip is significantly associated with type A. Cancers of the tongue, gum , and cheek also have a blood type A association. Cancers of the salivary glands are strongly associated with A, and weakly with B. The gain in cancers of A's in this group is basically at the expense of the O's who have substantial protection against this type of cancer. The salivary glands also appear to have an association with being a secretor.
In the chapter on digestion, we discussed the blood type A association with Barrett's esophagus---a preneoplastic change to the tissue of the esophagus. So, it is not surprising to find A's having an association with and being over represented in esophageal cancer. Non-secretors (and Lewis(a+b-) also have an association with this cancer. Blood type B also has a tendency to more cancers of the esophagus, while O's have a definate degree of protection.
As a general rule, a higher intensity of oral disease is found among non-secretors. When it comes to pre-cancerous, or cancerous changes to tissue of the mouth and esophagus, non-secretors seem to fair worse than secretors. This oral disease susceptibility is reflected in the occurrence of epithelial dysplasia, for example, which is found almost exclusively in the non-secretor group.
Vidas I, Delajlija M, Temmer-Vuksan B, et al. Examining the secretor status in the saliva of patients with oral pre-cancerous lesions. J Oral Rehabil 1999 Feb;26(2):177-82
Barrett's esophagus, a condition often preceding the development of esophageal cancer, and esophageal cancer also have a positive association with Lewis (a+b-) non-secretor phenotypes.
Torrado J, Ruiz B, Garay J, et al. Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett's esophagus. Am J Surg Pathol 1997 Sep;21(9):1023-9
For cancer of the larynx and hypopharynx, we again find an A and B (and AB in his case) association. The A2 blood type (a less common variant of blood type A) was significantly more frequent in group of patients with glottis cancer, while the A1B type was over represented in the group with hypopharynx cancer.
Pyd M, Rzewnicki I, Suwayach U. ABO blood groups in patients with laryngeal and hypopharyngeal cancer. Otolaryngol Pol 1995;49 Suppl 20:396-8
Structural changes to squamous cell cancers of the head and neck are quite common. In normal tissue of this region, your ABO blood type is expressed. However, once squamous cell cancer develops, the A antigen disappears in about 1/3 of A's and AB's, and the H (or O) antigen is expressed in carcinoma cells not only from all blood group O individuals, but from virtually all individuals of blood groups A, B and AB as well. The T and Tn antigens we discussed earlier also become commonly expressed in these cancers. So, in essence results suggest that the expression of the blood group-related H, T and Tn carbohydrate chains is a common sequel of squamous cell cancer of the head and neck. As a general rule, it appears that tumors expressing the H antigen (for blood types A, B, and AB) have a poor prognosis
Yokota M, Ito N, Hatake K, et al. Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine structures in squamous cell carcinomas of the head and neck. Histochem J 1997 Jul;29(7):555-62
Xie X, Boysen M, Clausen OP, Bryne MA. Prognostic value of Le(y) and H antigens in oral tongue carcinomas. Laryngoscope 1999 Sep;109(9):1474-80
BRAIN AND NERVOUS SYSTEM CANCERS
A positive, consistent, and often very strong association has been found between blood group A and brain and nervous system tumors. A weaker association for these forms of cancer exists for blood type B. Conversely, it has been a consistent finding that being a blood group O is a favorable prognostic factor for brain and nervous system cancers.
Zampieri P, Meneghini F, Grigoletto F, et al. Risk factors for cerebral glioma in adults: a case-control study in an Italian population. J Neurooncol 1994;19(1):61-7
Turowski K, Czochra M. ABO blood groups in glioblastoma multiforme. Neurol Neurochir Pol 1979 Mar-Apr;13(2):173-6 [Article in Polish]
Trouillas P, Menaud G, De The G, et al. Epidemiological study of primary tumors of the neuraxis in the Rhone-Alps region. Quantitative data on the etiology and geographical distribution of 1670 tumors. Rev Neurol (Paris) 1975 Oct;131(10):691-708 [Article in French]
An interesting note with regards to blood type occurs for malignant gliomas. Researchers investigating the use and efficacy of post-operative poly- and immunochemotherapy for this cancer decided to break results down by blood type. They found that when the efficacy of polychemotherapeutic and antibiotic intervention was analyzed by survival time, it was a promising intervention for blood type A and AB patients. However, it was ineffective in blood group O. Based on their results, the researchers concluded that an individual selection of the schedule of chemo- and immunochemotherapy should be selected by AB0 blood group.
Romodanov SA, Gnedkova IA, Lisianyi NI, Glavatskii AIa. Efficacy of chemotherapy and immunochemotherapy in neuro-oncologic patients of various blood groups. Zh Vopr Neirokhir 1989 Jan-Feb;(1):17-20 [Article in Russian]
While this is currently an isolated finding, it does draw attention to the possibility that medical interventions for cancer and possibly many diseases could be made better if blood type was a component of the information looked at to judge efficacy of treatments.
Arseni C, Danaila L, Constantinescu AI. Considerations on the correlation between the blood groups and the incidence of cerebral tumours. Rev Roum Neurol 1972;9(3):135-8
Arseni C, Danaila L, Constantinescu A. Correlations between the blood groups and the incidence of congenital neurosurgical diseases. Rev Roum Neurol 1971;8(5):335-8
Pearce KM, Yates PO. Blood groups and brain tumours. J Neurol Sci 1965 Sep-Oct;2(5):434-41
Alcantara A, Kinzel W, Bube FW, Uhlenbruck G. Blood groups and brain tumors. Zentralbl Neurochir 1965;26(2):156-65 [Article in German]
Blood type A is overrepresented in thyroid cancer, while blood type O appears to be protective in this form of cancer.
Klechova L, Gosheva-Antonova Ts. ABO and Rh blood group factors in thyroid gland diseases. Vutr Boles 1980;19:75-9
Similar to many other cancers, the fine structure of various antigens is altered between healthy and neoplastic cells. As a general rule, loss of blood group A and B antigens, and the appearance of greater numbers of Tn antigens, is a characteristic of thyroid cancers and is associated with a tendency for malignancy.
Gonzalez-Campora R, Garcia-Sanatana JA, et al. Blood group antigens in differentiated thyroid neoplasms. Arch Pathol Lab Med 1998 Nov;122(11):957-65
Larena A, Vierbuchen M, Schroder S, Larena-Avellaneda A, Hadshiew I, Fischer R. Blood group antigen expression in papillary carcinoma of the thyroid gland. An immunohistochemical and clinical study of expression of Lewis, ABO and related antigens. Langenbecks Arch Chir 1996;381(2):102-13
Only two studies have been conducted on skin cancer. In general, cancer of the skin appears to be strongly associated with blood type O. Blood type O has also been found to have the highest frequency of malignant melanoma. They also had the lowest average time of survival after diagnosis. Blood type A tended to have the longest survival times, with this trend particularly strong in blood type A women.
Karakousis CP, Evlogimenos E, Suh O. Blood groups and malignant melanoma. J Surg Oncol 1986 Sep;33(1):24-6
Bone cancers show the strongest association with blood type B, and a weaker association with blood type A. LEUKEMIA AND HODGKIN'S DISEASE Evidence suggests that in general, blood type A individuals are more predisposed to leukemia. This trend is particularly strong for a more rare variety of blood type A (the A2 A's) and chronic lymphocytic leukemia associated. Similarly, blood type O appears to grant a degree of resistance especially in acute leukemia. This protection is most noted among female O's. Because of this some researchers have suggested that there might be a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against acute leukemia.
Hodgkin's disease has shown an association with blood type O.
Janardhana V, Propert DN, Green RE. ABO blood groups in hematologic malignancies. Cancer Genet Cytogenet 1991 Jan;51(1):113-20
Nayak SK. ABO blood groups in different diseases. J. Ind Med 19971;87:449-52
Jackson N, Menon BS, Zarina W, Zawawi N, Naing NN. Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes. Ann Hematol 1999 May;78(5):233-6
Similar to other cancers we have dscussed, leukemia is often characterized by a loss of blood type antigens. And after induction of complete remission it is not uncomon for blood type to revert to normal and reappear on cells.
Xiros N, Northoff H, Anger B, Heit W, Heimpel H. Blood group change in a patient with blastic transformation of a myelodysplastic syndrome. Blut 1987 May;54(5):275-80
Atkinson JB, Tanley PC, Wallas CH. Loss of blood group A in acute leukemia. Morphologic and biochemical studies of red cells. Transfusion 1987 Jan-Feb;27(1):45-8
Uchikawa M. Alterations of ABH antigens in leukemic patients. Nippon Rinsho 1997 Sep;55(9):2369-73
Hafner V, Coatmelec M, Niculescu R. Temporary changes and permanent changes in the erythrocyte blood-group antigens in malignant hemopathies. Rom J Intern Med 1996 Jul-Dec;34(3-4):183-8
BLOOD TYPE AND CANCER: IN SEARCH OF SOME ANSWERS
Perhaps the greatest focus of current research on the ABO blood type antigens is in the field of molecular oncology. Recent findings in membrane chemistry, tumor immunology and infectious disease add a scientific rationale for several blood type associations and there is an increasing compelling rationale for some of the earlier statistical findings.
Garratty G. Association of blood groups and disease: do blood group antigens and antibodies have a biological role? Pubbl Stn Zool Napoli [II]. 1996;18(3):321-44.
The huge interest in blood type stems from the developing awareness that blood type antigens are incredibly important components in the process of cell maturation and control; for example the appearance or disappearance of blood type antigens is a hallmark of malignancy in many common cancers.
Several 'tumor antigens' or 'tumor markers' are the known product of certain blood type precursors. Many of these tumor antigens are 'A-like' which helps in part to explain the striking number of associations with blood type A and AB. On the contrary, auto-immune disorders tend to be associated with blood type O. The contrast with the cancer-type A association is an interesting one in view of the suggestion of earlier immunologists that there is a fundamental antithesis between the two classes of disease. In essence, the heightened surveillance and over-active immune activity, tends to result less malignancy, while overly tolerant immune activity tends to encourage it. These observations suggest a more general hypothesis that in the tissues of all people, both normal and cancerous, there are blood group A-like antigens present at a biochemical level which is usually inaccessible to the immune system. However, in the course of an auto-immune process or the immune response to a growing cancer, the antigen becomes accessible. At that point a blood type A person, who cannot make anti-A antibodies, will be more likely than an blood type O person to tolerate the cancer, but less likely than an O person to attack his own tissues
The cancer-type A link is far from absolute; several tumors show a consistent associations with O or B.
This implies that cancer is a condition associated with derangement of blood type activity in general,
and the expression of A-like antigens on the surface tumors is just simply the most common of theses