ABO blood group alleles and the risk of pancreatic cancer in a Japanese population

Abstract

Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants' two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non-O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r 2 = 0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk. (Cancer Sci 2011; 102: 1076-1080 T he incidence of pancreatic cancer (PC) is increasing in Japan, and this cancer is now the sixth leading cause of cancer death.(1,2) Early detection of PC in its operable stage is difficult and curative treatment such as complete surgical removal is limited, which together give PC a 5-year relative survival rate of only 5.5%.(3) This suggests that epidemiological approaches to predicting the risk of PC may play an important role in identifying PC high-risk groups and ultimately decreasing the number of PC deaths.Risk factors for PC include advancing age, smoking, obesity, diabetes mellitus, family history of PC, alcohol consumption and chronic pancreatitis. (2,(4)(5)(6)(7)(8) Recently, a large prospective cohort study also showed a statistically significant association between ABO blood type and risk of PC.(9) Specifically, this study suggested that people with blood type O have a lower risk of PC than those with blood type A, B or AB. A genome-wide association study (GWAS) comparing PC cases and controls (PanScan), which includes the forementioned prospective cohort study population, (9) identified a single-nucleotide polymorphism (SNP) within the first intron of the ABO gene (rs505922) that was associated with PC risk.(10) Furthermore, using almost the same population as PanScan, Wolpin et al. (11) reported that the ABO blood type could be inferred from two SNPs (rs505922 and rs8176746), and concluded the relationship between PC risk a...

A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population

“…An analysis of 94 subjects showed that the T allele of rs505922 was in strong linkage disequilibrium (LD; r 2 = 0.97) with the ABO gene encoding the O blood type, which produces non functional protein due to a singlenucleotide deletion in codon 87 (rs8176719), concordant with a previous report 27 . By using the geno typing results of two tagging SNPs, through which ABO alleles can be inferred (rs505922 and rs8176746; Supplementary Table 9) 27 , we could successfully determine the ABO blood type in 98.6% of samples 28 (Supplementary Table 10). Association analysis showed that individuals with blood type O exhibited significantly higher risk for duodenal ulcer than those with blood type A (P = 2.04 × 10 −6 ; OR = 1.43; Supplementary Table 10).…”

A and B Blood Group Antigens in Human Pancreatic Ductal Adenocarcinomas

“…In addition, several recent genome-wide association studies found that carriers of non-O blood groups are at higher risk of developing pancreatic adenocarcinoma than carriers of blood groups O, in agreement with epidemiologic studies of blood group antigens reported 50 years ago [1,2,3,4,5,6,7,8,9]. Further analysis of pancreatic cancer cohorts found that pancreatic risk was higher in subjects with blood group A allele subtypes associated with increased glycosyltransferase activity [10].…”

Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study

“…Cohort studies in independent populations confirmed a significant higher risk of developing sporadic pancreatic cancer in carriers of the blood group B. Carriers of blood groups A and AB exhibited an intermediate risk, and carriers of blood group O demonstrated the lowest risk 28––30. Compared with the OO genotype, addition of each non-O allele increased the pancreatic cancer risk.…”