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      The role of the histoblood ABO group in cancer

      review-article
      1 , * , 2
      Future Science OA
      Future Science Ltd
      cancer, histoblood ABO group, rs505922

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          Abstract

          Since the first link between blood type and cancer was described in 1953, numerous studies have sought to determine whether the histoblood ABO group is associated with tumorigenesis. In 2009, the first significant association between a SNP located within the ABO glycosyltransferase gene and increased risk of pancreatic cancer was reported. Here, we describe the history and possible functions of the histoblood ABO group and then provide evidence for a role of blood group antigens in the most common cancer types worldwide using both blood type and SNP data. We also explore whether confusion regarding the role of blood type in cancer risk may be attributable to heterogeneity within tumor types.

          Abstract

          Lay abstract:  ABO encodes the protein responsible for defining blood groups as A, B, AB or O. Despite over a century of investigation, it is not well known whether the blood group antigens have a function or if they contribute to human health. Over the last 60 years, associations between blood type and cancer risk have been reported, although the data have often been conflicting. To better understand the possible role of the ABO blood group in tumorigenesis, we review the data for the most common tumor types worldwide.

          Most cited references95

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          Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.

          We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
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            Molecular genetic basis of the histo-blood group ABO system.

            The histo-blood group ABO, the major human alloantigen system, involves three carbohydrate antigens (ABH). A, B and AB individuals express glycosyltransferase activities converting the H antigen into A or B antigens, whereas O(H) individuals lack such activity. Here we present a molecular basis for the ABO genotypes. The A and B genes differ in a few single-base substitutions, changing four amino-acid residues that may cause differences in A and B transferase specificity. A critical single-base deletion was found in the O gene, which results in an entirely different, inactive protein incapable of modifying the H antigen.
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              ABO blood group and the risk of pancreatic cancer.

              Other than several rare, highly penetrant familial syndromes, genetic risk factors for sporadic pancreatic cancer are largely unknown. ABO blood type is an inherited characteristic that in previous small studies has been associated with the risk of gastrointestinal malignancies. We separately examined the relationship between ABO blood type and the risk of incident pancreatic cancer in two large, independent, prospective cohort studies (the Nurses' Health Study and Health Professionals Follow-up Study) that collected blood group data on 107 503 US health professionals. Hazard ratios for pancreatic cancer by ABO blood type were calculated using Cox proportional hazards models with adjustment for other known risk factors, including age, tobacco use, body mass index, physical activity, and history of diabetes mellitus. All statistical tests were two-sided. During 927 995 person-years of follow-up, 316 participants developed pancreatic cancer. ABO blood type was associated with the risk of developing pancreatic cancer (P = .004; log-rank test). Compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted hazard ratios for incident pancreatic cancer were 1.32 [95% confidence interval {CI} = 1.02 to 1.72], 1.51 [95% CI = 1.02 to 2.23], and 1.72 [95% CI = 1.25 to 2.38], respectively). The association between blood type and pancreatic cancer risk was nearly identical in the two cohorts (P(interaction) = .97). Overall, 17% of the pancreatic cancer cases were attributable to inheriting a non-O blood group (blood group A, B, or AB). The age-adjusted incidence rates for pancreatic cancer per 100 000 person-years were 27 (95% CI = 23 to 33) for participants with blood type O, 36 (95% CI = 26 to 50) for those with blood type A, 41 (95% CI = 31 to 56) for those with blood type AB, and 46 (95% CI = 32 to 68) for those with blood type B. In two large, independent populations, ABO blood type was statistically significantly associated with the risk of pancreatic cancer. Further studies are necessary to define the mechanisms by which ABO blood type or closely linked genetic variants may influence pancreatic cancer risk.
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                Author and article information

                Journal
                Future Sci OA
                Future Sci OA
                FSO
                Future Science OA
                Future Science Ltd (London, UK )
                2056-5623
                June 2016
                15 March 2016
                : 2
                : 2
                : FSO107
                Affiliations
                [1 ]Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA 15963, USA
                [2 ]Clinical Breast Care Project, Murtha Cancer Center, 620 Seventh Street, Windber, PA 15963, USA
                Author notes
                *Author for correspondence: r.ellsworth@ 123456wriwindber.org
                Article
                10.4155/fsoa-2015-0012
                5137991
                28031957
                be281e6e-e65c-4d8d-8b46-ec0bad581506
                © Rachel Ellsworth

                This work is licensed under a Creative Commons Attribution 4.0 License

                History
                : 01 December 2015
                : 15 January 2016
                Categories
                Review

                cancer,histoblood abo group,rs505922
                cancer, histoblood abo group, rs505922

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