Relationship between ABO blood groups and skin cancersMersin University, Faculty Of Medicine, Department of Dermatology1, Hematology2, Plastic and Reconstructive Surgery3, Biostatistics 4. email@example.com
Umit Tursen MD1, E Naci Tiftik MD2, Sakir Unal MD3, Ozgur Gunduz MD4, Tamer Irfan Kaya MD1, Handan Camdeviren PhD4, Guliz Ikizoglu MD1
Dermatology Online Journal 11 (3): 44
Studies of associations between various cancers and the ABO blood groups have shown elevated relative risks for some categories of disease. To date, no report has evaluated the relationship between the ABO blood groups and the skin cancers. To investigate this association, we conducted a retrospective study of premalignant and malignant tumors diagnosed in Turkey. All tumors were histologically confirmed. Blood information was obtained for 98 individuals with premalignant and malignant skin tumors, and the distribution of ABO and Rh blood type for cases was compared with that of 419 healthy blood donors from the same geographic area. Although patients with blood group A were higher, group 0 lower than in controls, the differences were not significant. The distribution of Rh factor, blood group B and AB among cases and controls also did not differ significantly. We found a significant relationship between age and skin cancer (p=0.0001). Old patients had 1.238 times higher risk for skin cancer. Further studies in larger series on blood group antigens are needed to elucidate the relationship between these antigens and skin cancer.
Blood group antigens, which are the major alloantigens in humans, are present on the surface of red blood cells and various epithelial cells. As the majority of human cancers are derived from epithelial cells, changes in blood group antigens are an important aspect of human tumor [1, 2, 3, 4]. In some tumors, alteration of ABO/Lewis-related antigens is associated with malignant transformation [5-19].
The relationship with blood groups and incidence, clinicopathologic parameter and prognosis had been studied in many cancers such as esophagus, cardiac, gastric, lung, laryngeal, hypopharyngeal, salivary gland, gynecologic, colorectal, pancreatic, bone, urinary bladder, ureter, renal, breast, prostate, testicular tumors and uveal melanoma [5-19]. Additionally, ABO genes are distributed differently among socioeconomic groups and we know that socioeconomic status is one of the risk factors for disease . Therefore, we hypothesized that analysis of blood group and related antigens on skin cancers would provide useful information on the risk factors. To date, no report has evaluated the relationship between the ABO blood groups and the skin cancers. Thus, a retrospective assessment of the relation between blood groups and malignant and premalignant skin lesions was performed with a view to start the study of the genetics of these cancers in Turkey.
Material and methods
The study was approved by the Ethics Committee of the Medical Faculty of the University of Mersin. All the patients and controls accepted blood examination. Ninety eight patients with skin cancer including 23 squamous cell carcinoma (SCC), 42 basal cell carcinoma (BCC), 33 in situ squamous cell carcinoma (ISCC) and 419 control subjects were enrolled in this study. Control subjects were selected among healthy people with no history of cardiovascular disease, cancer, chronic degenerative neurologic disease, chronic obstructive pulmonary disease, hepatitis, allergies in general or alcohol abuse. The diagnosis of skin cancer was based on dermatopathologic examination. Documentation of clinical findings included: (a)Gender (b)Age (c)Clinic types of the skin cancer including SCC, BCC and ISCC and (d) tumor location.
Blood samples were obtained into vacuum tubes containing EDTA (vacutainer, Becton Dickinsen, Marseilles, France) from each donor's venous circulation. ABO and Rh blood typing were carried out with tube method and gel method.
Tube method: One drop of anti-A, anti-B, or anti-D (Eryclone, Tulip Diagnostics, Bambolim, India) was added to the appropriately labeled tube. A 5 percent suspension of red blood cells (RBC) was made in isotonic saline. 1 drop was added to tubes containing anti-A, anti-B, or anti-D. The contests of the tubes were mixed thoroughly, and the tubes were centrifuged for 20 seconds at 3400 rpm. Tubes were read macroscopically for agglutination.
Gel method: A 5 percent RBC suspension was prepared in diluent (modified bromelin solution for red cell suspensions). Gel cards (Diaclon ID, Diamed AG, Cressier, Switzerland) were used for ABO and Rh typing. 10 µL of RBC suspension was added to the gel microtubes containing anti-A, anti-B, anti-D, and control reagents, respectively. 50 µL of donor plasma were added to microtubes for reverse ABO group testing. The ID cards were centrifuged at 895 rpm 10 minutes in the centrifuges ( ID-centrifuge). A positive reaction (4+) was determined by the formation of a red line on the gel surface, whereas intermediate reactions were characterized by red agglutinates distributed throughout the gel. With a negative reaction, a compact button of cells formed on the bottom of the microtube.
Multivariate analysis was carried out by using a logistic regression model . Logistic regression analysis was chosen to study the predictive value of each risk factor such as sex, age and blood types. P values < 0.05 were regarded as statistically significant.
Among 98 subjects with skin cancer, the ABO blood types of A, B, 0 or AB were 45 (% 45), 15 (15 %), 30 (30 %) and 8 (8 %) respectively. For controls, the ABO blood types were 147 (35 %), 66(15 %), 188 (44 %) and 18 (4 %) respectively. The mean age was 53±6 (303 male, 116 female) for controls, and 63±14 (70 male, 28 female) for patients.
Although patients with blood group A were higher, group 0 lower than in controls, the differences were not significant. In our study, we could not find any significant relationship according to blood types in total patient group, and also among skin cancer types. (Tables 1-4). The distribution of Rh factor among cases and controls did not differ significantly. There was no difference in ABO blood group or Rh factor and tumor location and sex. We found a significant relationship between age and skin cancer (p = 0.0001). Old patients had 1.238 times higher risk for skin cancer.
Skin cancer is the most common type of cancer in humans. The etiopathogenesis of skin cancers is still unknown. Exposure to sunlight, particularly ultraviolet B radiation is a strong risk factor associated with skin cancer development. Other known risk factors include exposure to ionizing radiation, arsenicals, polyaromatic hydrocarbons, transplantation-associated immunosuppression and psoralen plus ultraviolet A therapy . The explanation for the association between ABO blood groups and some special diseases was still unclear. Many reports have shown that blood group antigen expression in tumor is correlated with metastasis and prognosis [23, 24]. The loss or presence of blood group antigens can increase cellular motility or facilitate the interaction between tumor cells and the endothelium of distant organs .
In our patients, we did not find any significant association with blood types. Although patients with blood group A were higher than in controls, there was no statistically significant. Some authors observed that A blood type was significantly more frequent in patients with laryngeal, hypopharinx, pancreatic, breast, testicular and bone cancers [9, 10, 13, 14, 16, 18]. To our knowledge, no report has evaluated the relationship between the ABO blood groups and the skin cancers. Jager et al. observed that no significant differences in survival or the development of metastases in patients with uveal melanoma regard to the ABO antigens . ABO blood group genes are map at 9q in which the genetic alteration is common in many cancers . Thus, ABO blood group antigen expression may be effected by the genetic change of tumors . On the other hand, it is possible the observed associations are not due to the blood group antigens themselves, but to the effects of genes closely associated with them. Additionally it might have nothing to do with molecular mechanisms or genetics. It is merely the result of population history, environment, diet and customs . In conclusion, our study shows no significant association of ABO blood groups with skin cancers. Further studies on blood group antigens in larger series are needed to elucidate the relationship between blood group antigens and skin cancers.
References1. Dabelsteen E. Cell surface carbohydrates as prognostic markers in human carcinomas. J Pathol 1996; 179:358-69.
2. Hakomori S. Tumor-associated carbonhydrate antigens. Ann Rev Immunol 1984; 2:103-26.
3. Lee JS, Ro JY, Sahin AA, Hong WK, Brown BW, Mountain CF, et al. Expression of blood-group antigen A-a favorable prognostic factor in non-small-cell lung cancer. N Engl J Med 1991; 324:1084-90.
4. Coon JS, Weinstein RS. Blood group-related antigens as markers of malignant potential and heterogeneity in human carcinomas. Hum Pathol 1986; 17:1089-106.
5. Su M, Lu SM, Tian DP, Zhao H, Li XY, Li DR, Zheng ZC. Relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaosan inhabitants of China. World J Gastroenterol 2001; 7:657-661.
6. Nakagoe T, Fukushima K, Nanashima A, Sawai T, Tsuji T, Jibiki MA, et al. Comparison of the expression of ABH/Lewis-related antigens in polypoid and non-polypoid growth types of colorectal carcinoma. J Gastroenterol Hepatol 2001; 16:176-183.
7. You WC, Ma JL, Liu WD, Gail MH, Chang YS, Zhang L, et al. Blood type and family cancer history in relation to precancerous gastic lesions. Int J Epidemiol 2000; 29:405-407.
8. Graziano SL, Tatum AH, Gonchoroff NJ, Newman NB, Kohman LJ. Blod group antigen A, and flow cytometric analysis in resected early-stage non-small cell lung cancer. Clin Cancer Res 1997; 3:87-93.
9. Pyd M, Rzewnicki I, Suwayach U. ABO blood groups in patients with laryngeal and hypopharyngeal cancer. Otolaryngol Pol 1995; 49:396-8.
10. Pinkston JA, Cole P. ABO blood groups and salivary gland tumors (Alabama, United States). Cancer Causes Control 1996; 7:572-4.
11. Marinaccio M, Traversa A, Carioggia E, Valentino L, Coviella M, Salamanna S, et al. Blood groups of the ABO system and survival rate in gynecologic tumors. Minerva Ginecol 1995; 47:69-76.
12. Juhl BR. Blood group antigens in transitional cell tumors of the urinary bladder. An immunohistochemical study. Dan Med Bull 1994; 41:1-11.
13. Vioque J, Walker AM. Pancreatic cancer and ABO blood types: a study of cases and controls. Med Clin (Barc.) 1991; 96:761-4.
14. Jia DX. Bone tumor and ABO blood type. Zhonghua Zhong Liu Za Zhia 1991; 13:220-2.
15. Cordon-Cardo C, Reuter VE, Finstad CL, Sheinfeld J, Lloyd KO, et al. Blood group-related antigens in human kidney: modulation of Lewis determinants in renal cell carcinoma. Cancer Res 1989; 49:212-8.
16. Anderson DE, Haas C. Blood type A and familial breast cancer. Cancer 1984; 54:1845-9.
17. Walker PD, Karnik S, de Kerion JB, Pramberg JC. Cell surface blood group antigens in prostatic carcinoma. Am J Clin Pathol 1984; 81:503-6.
18. Jordan GH, Lynch DF. Relationship of blood group to testicular carcinoma. Urology 1983; 22:265-7.
19. Jager MJ, Völker-Dieben HJ, De Wolff-Roundaal D, Kakebeeke-Kemme H, DÕAmaro J. Possible relation between HLA and ABO type and prognosis of uveal melanoma. Documente Ophthalmologica 1992; 82:43-47.
20. Petrakis NL, King MC. Genetic markers and cancer epidemiology. Cancer 1977; 39:1861-1866.
21. Hosmer DW, Lemeshow S. Applied Logistic Regression. New York: John Wiley & Sons, 1990.
22. Armstrong BK, Kricker A. Skin Cancer. Dermatol Clin 1995; 13:583-594.
23. Nakagoe T, Nanashima A, Sawai T, Tuji T, Ohbatake M, Jibiki M, Yamaguchi H, et al. Expression of blood group antigens A, B, and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients. J Cancer Res Clin Oncol 2000; 126:375-382.
24. Moldvay J, Scheid P, Wild P, Nabil K, Siat J, Borrelly J, et al. Predictive survival markers in patients with surgically resected non-small cell lung carcinoma. Clin Cancer Res 2000; 6:1125-1134.
25. Ichikawa D, Handa K, Hakomori S. Histo-blood group A/B antigen deletion /reduction vs. continuous expression in human tumor cells as correlated with their malignancy. Int J Cancer 1998; 76:284-289.
26. Hu N, Roth MJ, Polymeropolous M, Tang ZZ, Emmert-Buck MR, Wanf QH, et al. Identification of novel regions of allelic loss from a genome wide scan of esophageal squamous cell carcinoma in a high risk Chinese population. Genes Chromosomes Cancer 2000; 27:217-228.
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