Evaluation of risk factors for extrahepatic cholangiocarcinoma: ABO blood group, hepatitis B virus and their synergism

Abstract

Little is known about the role of association between ABO blood group and development of extrahepatic cholangiocarcinoma (ECC) through effects on hepatitis B viral (HBV) infection. Our aim was to address this question using a matched case-control study in Southern China.We prospectively analyzed 239 ECC patients, and 478 age-and sex-matched controls in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from 1999 to 2011. Information on ABO blood group, HBV infection and other clinicopathologic factors was collected. Adjusted odds ratios (AORs) and the corresponding 95% confidence intervals (CIs) were computed from unconditional logistic regression models, adjusted for major confounding factors. The estimated AORs were as follows: A blood group, 1.784; HBsAg1/HbcAb1, 1.848 and HBsAg2/HbcAb1, 1.501. The A blood type had a significant effect on modifying the risk of ECC among subjects with HBsAg1/HbcAb1 (AOR 3.795, 95% CI 1.427-10.090). ECC patients with A blood group were more common in younger subjects, and a lower proportion of serum CA-125 and CA19-9 elevation in patients with blood type A was found. Our study suggests an association between A blood type, HBV infection and ECC risk, and a synergism between A blood type and HBV infection in the development of ECC.Cholangiocarcinoma (CC) is a malignant neoplasm of the biliary-duct system accounting for 10-25% of the primary hepatic malignancies worldwide.1 Recent study showed that the incidence and mortality rates of CC have been increasing worldwide including China.2-6 Although several risk factors for CC, including parasitic infection, primary sclerosing cholangitis, anatomical abnormalities and hepatolithiasis, have been established, some potential factors such as hepatitis virus infection and host genetic polymorphisms remain debating. 7 Meanwhile, data showed that potential risk factors might have different effect on CC, depending on the anatomical site. 8 The role of HBV in ECC is not entirely clear, and the related studies have different conclusions. 7 The prevalence rate of infection with hepatitis B virus (HBV) varies widely among different parts of the world; it can range from near zero to more than 10%.9 China is a typical highly endemic area of HBV infection. The effect of HBV infection on the incidence, age or sex distribution and clinicopathologic parameters of intrahepatic cholangiocarcinoma (ICC) has been documented by many studies, but the role of HBV in the development of extrahepatic cholangiocarcinoma (ECC) in viral hepatitis B endemic areas was less reported and remains to be addressed.Furthermore, several genome-wide studies demonstrated that ABO blood group antigens may alter the systemic inflammatory response. And, blood antigens are also known

HBV Infection Status and the Risk of Cholangiocarcinoma in Asia: A Meta-Analysis

“…Among the 39 studies, 26 studies were for ICC, including 13 studies [11–14, 16, 17, 19, 22, 23, 25, 26, 29, 31] for estimating the incidence rates of ICC, 11 studies [32, 34–36, 39–42, 44, 45, 47] for unadjusted OR analysis, and 7 studies [32, 35, 36, 39, 41, 42, 44] for adjusted OR analysis (Tables 3 and 4). Nine studies were for ECC, including 3 studies [11, 15, 20] for estimating the incidence rates of ECC, 5 studies [32, 35, 40, 43, 47] for unadjusted OR analysis, and 1 study [35] for adjusted OR analysis (Tables 4 and 5). The main features of included studies were shown in Tables 1 –5.…”

“…For pooled analysis of unadjusted OR of ECC with HBV infection, 6 studies with 14 517 participants including controls were analyzed [15, 32, 35, 40, 43, 47]. The meta-analysis in a random-effects model ( P < 0.001, I 2 = 88.6%) found no statistically significant increased risk of ECC incidence with HBV infection (OR = 1.407, 95% CI 0.925–2.141, P = 0.110, Figure 4(b)).…”

Evaluation of the relationship between ABO/Rh blood groups and severity of liver fibrosis in patients with chronic hepatitis B

“…Hazendonk et al, (30) in their study evaluating the extent and predictors of underdosing and overdosing in perioperative hemophilia A patients, found that blood O patients had a higher risk of perioperative bleeding complications compared to those with blood group non-O. A synergism between blood group A and HBV infection in the development of extrahepatic cholangiocarcinoma has been suggested (31). In their case-control study including 1.538 patients with newly diagnosed HCC, Shim et al (6) from Korea have concluded that blood group A and genotype AA showed the highest risk of HCC.…”

Association between ABO Genotype and Risk of Hepatocellular Carcinoma in Koreans

“…Fourth, risk sharing between each primary cancer site and anatomically adjacent organs is also useful regarding the potential mechanism. An association between blood group A, HBV infection, and extrahepatic cholangiocarcinoma (ECC) risk was reported, with synergism between blood group A and HBV infection in the development of ECC (Zhou et al, 2013).…”