|Home | About | Journals | Submit | Contact Us | Français|
Chronic Helicobacter pylori (H. pylori) infection is a major gastric adenocarcinoma (GA) risk factor. GA disproportionately affects U.S. Hispanics compared with non-Hispanic Whites (NHWs). Since H. pylori infection studies in Hispanics are few, infection rates in Hispanic and NHW men in Bexar County were compared, and relationships with ethnicity and obesity examined. Age- and zip code-matched participants from a community-dwelling cohort were randomly selected. Sera from 284 men were analyzed by enzyme immunoassay for H. pylori antibodies. Adjusted risk ratio estimation for matched data was conducted to identify differences. Hispanics had a markedly higher prevalence of infection (30.3%) than NHWs (9.2%). Matched risk ratio (mRR) analyses revealed a strong association between H. pylori seropositivity and Hispanic ethnicity (mRR = 3.31; 95% CI [1.91, 5.73], adjusted by BMI, smoking status, and family history of cancer (mRR range = 3.28-3.89). BMI mRRs (range = 1.19-1.22) were significant in all models. In this cohort, Hispanic men had higher H. pylori infection rates than NHWs, and parallel the disproportionately higher rates of GA; obesity contributes to this higher prevalence. Future studies should address country of origin, acculturation, and other factors influencing obesity to further elucidate risk of GA in Hispanic populations.
Gastric adenocarcinoma (GA), which accounts for over 90% of all gastric cancers (Blaser et al., 1995), affects U.S. Hispanics disproportionately compared with non-Hispanic Whites (NHWs; American Cancer Society, 2015). Studies in Texas have reported that GA incidence among Hispanics is more than twice as high as among NHWs (11.4 vs. 4.7 per 100,000 from 2005 to 2009; Ramirez, Thompson, & Vela, 2013). Data from 1995 to 2010 indicate that Hispanics have a fourfold higher risk of GA compared with NHWs (Munoz, Westin, Long Parma, Suarez, & Ramirez, 2015; Texas Department of State Health Services, 2013), and these results mirror national data (National Cancer Institute, 2013). Hispanics are one of the largest minority groups in the United States, comprising 17.1% of the general population (U.S. Census Bureau, 2014), and will grow to an estimated 31% by 2060 (U.S. Census Bureau, 2013a). In 2009, cancer surpassed cardiovascular disease as the primary cause of mortality in Hispanics (Siegel, Naishadham, & Jemal, 2012). Thus, the causes and control of GA in Hispanics should be a major public health focus (Ramirez, 2013; Ramirez et al., 2005).
Chronic infection with the bacterium Helicobacter pylori (H. pylori) is thought to be a major cause of GA (Blaser et al., 1995; Graham, 2015). GA can be subdivided into two distinct morphologic types, intestinal and diffuse, both of which have been previously associated with H. pylori infection (Gonzalez et al., 2012). H. pylori is also the most important pathogenic factor for the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In one report, 92% to 98% of patients diagnosed with MALT lymphoma were also positive for H. pylori (Testerman & Morris, 2014). As with GA, rates of gastric MALT lymphoma are significantly elevated in Hispanics who reside in South Texas compared with NHWs (RR = 1.82; Munoz et al., 2015). Thus, the study of H. pylori infection in Hispanic populations is of compelling interest.
H. pylori infection has also been linked to other cancers, including colorectal, lung, and prostate (Adriani, Repici, Hickman, & Pellicano, 2014; Franceschi, Tortora, Gasbarrini, & Gasbarrini, 2014; Garcia-Gonzalez et al., 2015; Wu, Yang, Xu, Gao, & Fan, 2013). However, the data are conflicting, particularly for colorectal cancer (Kapetanakis et al., 2012; Patel et al., 2014; Tatishchev, Vanbeek, & Wang, 2012).
The overall prevalence of H. pylori infection in the United States ranges from 14% to 31% in gastric biopsy specimens (Sonnenberg, Lash, & Genta, 2010), and according to National Health and Nutrition Examination Survey data (Grad, Lipsitch, & Aiello, 2012), Hispanics were three times as likely to be infected as NHWs (64% vs. 21%; American Cancer Society, 2015). In a prospective cohort study of over 1,200 Mexican Americans in San Antonio, Texas, the H. pylori seroprevalence rate was 57%. Being older and having a lower education level were significant predictors of H. pylori seropositivity (Rubicz et al., 2011). Despite the growing awareness of the high prevalence of H. pylori infection in Hispanics, few studies have examined risk factors related to these infection rates among Hispanics. This paucity of data is likely due to the fact that H. pylori infection is not reportable (Adams et al., 2013), and testing is not recommended in asymptomatic individuals (Malfertheiner et al., 2012).
Changes in gut microbiota have been implicated in development of metabolic disorders like obesity, but how H. pylori and gut microbiota act together to regulate human metabolism is unknown (Yang & Sheu, 2016). In one study of patients undergoing gastric banding, H. pylori infection was twice as common in Hispanics as in their NHW counterparts (36% vs. 15%; Portocarrero, Olafsson, Jackson, Doss, & Malamud, 2012). However, the groups did not differ with respect to other risk factors, such as alcohol or tobacco consumption, or proton pump inhibitor medication use.
The purpose of the present study was to determine and compare H. pylori infection rates in a cohort of healthy Hispanic and NHW men from San Antonio, Texas, and to correlate these rates with known and potential GA risk factors, including age and obesity (Lin et al., 2014), low socioeconomic status (Malfertheiner et al., 2012; Sokic-Milutinovic, Alempijevic, & Milosavljevic, 2015), tobacco use (Ladeiras-Lopes et al., 2008; Ramirez et al., 2013), and family history of specific cancers (Sokic-Milutinovic et al., 2015). The study focused on men because of their higher rates of gastric cancer (American Cancer Society, 2015), in an existing community-living cohort with a large proportion of Hispanic participants (Beuten et al., 2010).
Frozen serum samples were obtained from men enrolled in the San Antonio center for Biomarkers of Risk of prostate cancer (SABOR), an Early Detection Research Network–sponsored Clinical Validation Center supported by the National Cancer Institute (Beuten et al., 2010). Using simple random sampling without replacement, a cohort of 332 men were identified (166 Mexican American/Hispanic, 166 NHW) who were still alive at the time samples were obtained and had no personal history of prostate cancer, and matched for age and zip code. SABOR policy restricts access to blood samples of prostate cancer patients, so those were excluded from this analysis. Otherwise, participants with at least four blood draws were included to ensure adequate serum availability and maximum availability of data. The second-most recent annual study visit was selected to obtain survey data and sera. Data for this study were collected from September 2013 through May 2014. The institutional review board of the University of Texas Health Science Center at San Antonio approved this study.
Of the 332 cohort members selected for this study, serum samples were available for 284 (85.5%) participants from the selected study visit. These samples were analyzed by enzyme immunoassay (ELISA) to determine anti-H. pylori IgG antibody titers (HpG Screen ELISA Kit; ALPCO, Salem, NH). Briefly, the samples were diluted 1:200 and run in duplicate 100 µL volumes. As per the manufacturer’s instructions, optical densities (measured at 450 nm) greater than the standard (6.25 U/mL + 10% = 6.875) were considered positive.
Deidentified clinical data were abstracted from study charts and the SABOR electronic database. Data elements assessed included age, ethnicity, and body mass index (BMI). Additional risk factor information, like income, tobacco use history, and family history of cancer, was gathered from survey data of a subset of 99 participants (matched pairs), 55 of whom were H. pylori antibody-positive.
Descriptive statistics were used to summarize sample characteristics, and covariate balance across groups was confirmed by performing independent two-sample t and chi-square tests for continuous and categorical variables, respectively. Matched and covariate-adjusted risk ratios (mRR) and their corresponding 95% confidence intervals (95% CI) were estimated using conditional Poisson regression models with a robust variance estimator (Cummings, 2011) to evaluate the relationship between H. pylori serostatus and contributing variables. All analyses were conducted using Stata version 13 (StataCorp. 2014, College Station, TX).
Demographics for men whose samples were used in this study are reported in Table 1. The mean age and BMI were 65.0 (SD = 7.5) and 28.7 (SD = 4.8), respectively. Most participants were from Bexar County (92.3%). There were no significant differences between Hispanics and NHWs with respect to matching variables (age and county of residence). However, mean BMI was significantly higher in Hispanic participants compared with NHW participants, while significantly more NHWs than Hispanics had a BMI in the normal range. The analysis of additional risk factor data obtained from a subset of 49 Hispanics and 50 NHWs showed no significant differences between ethnic groups in relation to income, smoking status, or family history of cancer. Mean age (65.5; SD = 6.4) and BMI (28.2; SD = 3.8) of the participants in this subset did not differ from the larger cohort (data not shown).
Almost 20% (56) of samples tested were positive for the H. pylori IgG antibody. Infection rates among Hispanics were three times higher than among NHWs, and a strong association between H. pylori seropositivity and Hispanic ethnicity was observed, in both the full sample (mRR [95% CI] 3.31 [1.91, 5.73]) and the subsample (3.23 [1.86, 5.6]; Table 2). Both younger (age 49-64; mRR [95% CI] 4.25 [1.69, 10.67]) and older (70-79; 5.67 [1.89, 17]) Hispanics were at significantly higher risk for infection than NHWs. In addition, the subsample analysis demonstrated that Hispanics with lower annual incomes had 4 to 5 times higher risk of infection than NHWs (4.5 [1.13, 18] for income <$36,000; 5.5 [1.38, 22] for $40,000-$50,000). Hispanics with family history of cancer were at higher risk of infection compared with NHWs (4.5 [1.13, 18]). Likewise, there was a trend toward significant infection risk for past and current Hispanic smokers relative to their NHW counterparts (2.33 [0.99, 5.49]).
Hispanic ethnicity remained a significant predictor of H. pylori seropositivity after adjusting for BMI, smoking status, and family history of cancer. Hispanics were almost four times more likely to be H. pylori seropositive than NHWs, after adjusting for all three risk factors (Table 3). BMI remained a significant factor independent of ethnicity (mRR 1.19 [1.07, 1.32]), and in all the models where it was included.
In an existing cohort of Hispanic and NHW men, an overall H. pylori infection rate of 20% was identified, which was consistent with recent regional findings (Patterson, Straten, & Jimenez, 2012). Sonnenberg et al. (2010) reported that gastric biopsies from Texas residents had an overall infection rate of 12.7%. A study done in central Texas reported a prevalence of 24% in persons aged 41 to 60 years compared with other age groups (Patterson et al., 2012), but results were not stratified by ethnicity. As expected, the infection rate among Hispanics was much higher than NHWs (30% vs. 9%), consistent with previous reports of national data (Grad et al., 2012). The elevated infection rate among Hispanics was independent of BMI, smoking status, or family history of cancer. After adjusting for all other contributing variables, Hispanics had almost 4:1 risk of H. pylori infection relative to NHWs. The overall infection rate in the current sample was 20%, lower than national (31%) and regional (24%) seroprevalence rates despite similar timing of exposure to H. pylori across studies. Thus, the current results warrant further investigation into environmental and biological factors that could influence infection in heterogeneous populations.
The seropositivity rate of the Hispanics in this study (30%), although similar to that in another study including obese Hispanics (Portocarrero et al., 2012), is lower than a previous report of 57% seropositivity using the same antibody test among Mexican Americans in the San Antonio Family Heart Study (Rubicz et al., 2011). The discrepancy between these results may be explained by a previous comparative study between SABOR and San Antonio Family Heart Study cohorts by Beuten et al. (2011). Analyses of genetic admixtures of Hispanics from both cohorts revealed significant differences in the proportions of European and Native American ancestry. This variation is a potential contributing factor to susceptibility to H. pylori infection. Analysis of ethnic ancestry and seropositivity in Hispanics and NHWs in the SABOR cohort could help elucidate the contribution of ethnicity to H. pylori infection rate and risk of gastric cancer.
Elevated BMI was also observed to increase the risk for H. pylori seropositivity. This may seem counterintuitive given H. pylori’s negative effects on ghrelin, and therefore appetite, levels (Weigt & Malfertheiner, 2009). H. pylori eradication studies have reported increases in both ghrelin levels and growth in infected children (Yang, Sheu, Yang, Lu, & Chuang, 2012); however, the overall interaction of infection with the brain–gut axis is likely more complex (Budzynski & Klopocka, 2014). Nevertheless, future studies should be geared toward investigating the link between obesity and H. pylori as a potential mediator for the development of GA in this region, given the high obesity rates in STX (37.9% of Hispanics vs. 24.6% of NHWs) and Texas (35.2% of Hispanics vs. 25.2% of NHWs; Ramirez et al., 2013; Texas Department of State Health Services, 2013).
This study has some limitations. Data on tobacco use, income, and family history of cancer was obtained from only 99 participants. The sample size was too small to determine risk differences for specific cancers, with the exception of prostate for which no difference between ethnic groups was observed. Due to imputation of income from geographic location, which was matched for each pair of participants in the study, the analysis in Table 3 could not be adjusted by income. Such an analysis in a future study would be of great interest. Data on acculturation, generational status, and country of origin were not available. These variables can influence diet, gut bacteria, and metabolic processes, such as obesity, that are associated with cancer, and should be included in future studies. In addition, the study cohort excluded women, and gastric cancer is more than twice as prevalent in Hispanic women compared with NHW women (American Cancer Society, 2015; Ramirez et al., 2013). The minimum eligible age of SABOR participants (50 years) means the finding of gastric cancer among younger Hispanics (Al-Refaie et al., 2008) cannot be linked to H. pylori serostatus nor can other findings (Patterson et al., 2012) of higher infection rates among 41- to 60-year-olds compared with other age groups be corroborated. Additional studies with larger samples and multicohort comparisons are needed to further characterize H. pylori infection among Hispanics. Case-control studies are also needed to determine the proportion of gastric cancer cases related to H. pylori in Hispanics. The results of these future investigations could help inform effective primary surveillance and prevention approaches, not only for reducing risk of gastric cancer but more proximal health outcomes like peptic ulcer disease and atrophic gastritis (a precursor of gastric cancer; Malfertheiner et al., 2012) in this underserved population.
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by a pilot award through Redes En Acción: The National Hispanic Cancer Research Network, under the auspices of the National Cancer Institute (NCI; U54 CA153511 to DLP and AGR); the Institute for Health Promotion Research (IHPR); and the Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center at San Antonio, an NCI-designated Cancer Center (P30CA054174). The SABOR cohort study is supported by NCI U01 CA086402 to IMT.