Reply to High hepatocellular carcinoma risk among US‐born Hispanics

We appreciate the interest from Ponzetto and Figura regarding our article reporting the unexplained greater incidence of hepatocellular carcinoma (HCC) in US-born Hispanic men. Ponzetto and Figura proposed that Helicobacter pylori, particularly the cytotoxin-associated gene A (CagA) strain, might be responsible for the excess risk of HCC observed among US-born Hispanic men. Waluga et al recently summarized the current knowledge regarding the possible role of H. pylori infection and other Helicobacter species in the etiology of liver disease, including HCC. The proposed mechanisms through which H. pylori impacts the development of HCC are undoubtedly complex, and some studies have supported the involvement of H. pylori in the pathogenesis of HCC, whereas others have not. A 2005 study demonstrated that the prevalence of H. pylori infection among Hispanics in California has declined with more recent generations in the United States. Hispanic immigrants were found to have the highest prevalence (31%), whereas first-generation US-born Hispanic individuals had an intermediate prevalence (9%) and second-generation US-born Hispanic individuals had the lowest prevalence (3%). Earlier studies also have demonstrated that being born in a developing country is an important risk factor for H. pylori infection. Based on these data, if H. pylori played a significant role in HCC etiology, we would expect the incidence rates of HCC in non-US-born Hispanics to be higher, not lower as we observed, than in US-born Hispanics. In addition to Hispanics, the Multiethnic Cohort study also includes African American, Japanese American, Native Hawaiian, and white individuals. The incidence rates of HCC vary across these groups, with Latinos having the highest incidence, followed by Native Hawaiians, African Americans, Japanese Americans, and whites. The prevalence of H. pylori infection also varies by race/ethnicity. The prevalence of H. pylori infection is high in Hispanics, but African American individuals also have a high prevalence. Although there are many limitations to using Medicare claims data to estimate H. pylori infection, in the Multiethnic Cohort study, we observed that the prevalence of H. pylori infection in African American and Japanese American individuals was similar to that in Hispanics. With regard to CagA strain, the prevalence of CagA among African American individuals who are positive for H. pylori has been found to be very high (up to 90%), and higher than in Hispanics. Furthermore, the prevalence of CagA has been shown to be higher among individuals born in developing countries compared with those born in developed countries. From an epidemiologic standpoint, these observations do not appear to support that H. pylori, particularly CagA, is responsible for the excess risk of HCC observed among US-born Hispanic men. Nonetheless, we acknowledge that the hypothesis is interesting and should be explored further in our cohort and other populations.