Sex and ethnic/racial-specific risk factors for gallbladder disease.

BACKGROUND: Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations. METHODS: We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993-2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders. RESULT: After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m2, diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42). CONCLUSION: Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.

Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom.

OBJECTIVES: The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS: A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS: A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS: Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.

Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease.

OBJECTIVE: Our center previously reported its experience with pediatric gallbladder disease and cholecystectomies from 1980 to 1996. We aimed to determine the current clinical characteristics and risk factors for symptomatic pediatric gallbladder disease and cholecystectomies and compare these findings with our historical series. STUDY DESIGN: Retrospective, cross-sectional study of children, 0 to 18 years of age, who underwent a cholecystectomy from January 2005 to October 2008. RESULTS: We evaluated 404 patients: 73% girls; 39% Hispanic and 35% white. The mean age was 13.10 ± 0.91 years. The primary indications for surgery in patients 3 years or older were symptomatic cholelithiasis (53%), obstructive disease (28%), and biliary dyskinesia (16%). The median BMI percentile was 89%; 39% were classified as obese. Of the patients with nonhemolytic gallstone disease, 35% were obese and 18% were severely obese; BMI percentile was 99% or higher. Gallstone disease was associated with hemolytic disease in 23% (73/324) of patients and with obesity in 39% (126/324). Logistic regression demonstrated older age (P = .019) and Hispanic ethnicity (P < .0001) as independent risk factors for nonhemolytic gallstone disease. Compared with our historical series, children undergoing cholecystectomy are more likely to be Hispanic (P = .003) and severely obese (P < .0279). CONCLUSION: Obesity and Hispanic ethnicity are strongly correlated with symptomatic pediatric gallbladder disease. In comparison with our historical series, hemolytic disease is no longer the predominant risk factor for symptomatic gallstone disease in children.

Autosomal genome-wide linkage analysis to identify loci for gallbladder wall thickness in Mexican Americans.

The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 +/- SE = 0.38 +/- 0.09, P < 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24-q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.

A genomewide search finds major susceptibility loci for gallbladder disease on chromosome 1 in Mexican Americans.

Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0-5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome 1p between markers D1S1597 and D1S407 (1p36.21) and near marker D1S255 (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD >or=1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans.

Caring for a limited-English proficient patient.

Each day in the United States, health care workers try to communicate with patients who are deaf, hard of hearing, or limited-English proficient (LEP). According to government regulations, these patients are guaranteed access to language accommodations. The legal implications of these regulations will be discussed along with ways to facilitate communication with patients who are deaf, hard of hearing, or LEP and the requirements for those who act as interpreters for such patients.

Food intake patterns and gallbladder disease in Mexican Americans.

OBJECTIVE: Results of previous studies on diet and gallbladder disease (GBD), defined as having gallstones or having had surgery for gallstones, have been inconsistent. This research examined patterns of food intake in Mexican Americans and their associations with GBD. DESIGN: Cross-sectional. SUBJECTS: The study population included 4641 Mexican Americans aged 20-74 years who participated in the 1988-94 third National Health and Nutrition Examination Survey (NHANES III). GBD was diagnosed by ultrasound. Food intake patterns were identified by principal components analysis based on food frequency questionnaire responses. Component scores representing the level of intake of each pattern were categorized into quartiles, and prevalence odds ratios (POR) were estimated relative to the lowest quartile along with 95% confidence intervals (CI). RESULTS: There were four distinct patterns in women (vegetable, high calorie, traditional, fruit) and three in men (vegetable, high calorie, traditional). After age adjustment, none were associated with GBD in women. However, men in the third (POR = 0.42, 95%CI 0.21-0.85) and fourth (POR = 0.53, 95%CI 0.28-1.01) quartiles of the traditional intake pattern were half as likely to have GBD as those in the lowest quartile. CONCLUSIONS: These findings add to a growing literature suggesting dietary intake patterns can provide potentially useful and relevant information on diet-disease associations. Nevertheless, methods to do so require further development and validation.

Country of birth and prevalence of gallbladder disease in Mexican Americans.

OBJECTIVES: This research sought to describe the association between country of birth and gallbladder disease (GBD) in Mexican Americans, identify subgroups at especially high risk, and identify risk factors that may mediate a birthplace-GBD association. DESIGN: Cross-sectional. METHODS: Our study population included 4157 Mexican Americans aged 20-74 who participated in the 1988-94 third National Health and Nutrition Examination Survey. GBD was diagnosed by ultrasound. Information on country of birth, education, income, and selected GBD risk factors was obtained from interviews. Prevalence odds ratios (POR) for GBD in Mexico- vs. US-born Mexican Americans were estimated by unconditional logistic regression, along with 95% confidence intervals (CI). To evaluate the extent to which GBD risk factors mediated the birthplace-GBD association, PORs for country of birth were compared in models with and without additional covariates. RESULTS: Age-adjusted GBD prevalence was lower in Mexico- than in US-born Mexican-American women (POR = 0.70, 95% CI 0.50, 0.98) and men (POR = 0.63, 95% CI 0.40, 0.97). The difference was especially pronounced among subjects of lower socioeconomic status. Despite substantial differences in GBD risk factor distributions by birthplace, none could completely explain the prevalence difference. CONCLUSIONS: The observation that GBD prevalence is higher among US-born Mexican Americans is consistent with research showing poorer health in this group. Further research is needed to identify strategies for reducing morbidity from GBD in Mexican Americans.

Prevalence and ethnic differences in gallbladder disease in the United States.

BACKGROUND & AIMS: Gallbladder disease is one of the most common conditions in the United States, but its true prevalence is unknown. A national population-based survey was performed to determine the age, sex, and ethnic distribution of gallbladder disease in the United States. METHODS: The third National Health and Nutrition Examination Survey (NHANES III) conducted gallbladder ultrasonography among a representative U.S. sample of more than 14, 000 persons. The diagnosis of gallbladder disease by detection of gallstones or cholecystectomy was made with excellent reproducibility. RESULTS: An estimated 6.3 million men and 14.2 million women aged 20-74 years had gallbladder disease. Age-standardized prevalence was similar for non-Hispanic white (8. 6%) and Mexican American (8.9%) men, and both were higher than non-Hispanic black men (5.3%). These relationships persisted with multivariate adjustment. Among women, age-adjusted prevalence was highest for Mexican Americans (26.7%) followed by non-Hispanic whites (16.6%) and non-Hispanic blacks (13.9%). Among women, multivariate adjustment reduced the risk of gallbladder disease for both Mexican Americans and non-Hispanic blacks compared with non-Hispanic whites. CONCLUSIONS: More than 20 million persons have gallbladder disease in the United States. Ethnic differences in gallbladder disease prevalence differed according to sex and were only partly explained by known risk factors.

Genetic determinants of variation in gallbladder disease in the Mexican-American population.

Since there have not been any studies that quantify the influence of genetic factors on gallbladder disease (GBD) in humans using information from families, we utilized pedigree data to explore the genetic control of variation in liability to GBD. Using an extension of a variance components approach, we performed genetic analyses of GBD using information from 32 low-income Mexican-American families with two slightly different general models incorporating several sex-specific GBD risk factors. After evaluating the relative magnitudes of the covariate effects from these two models, we identified a parsimonious model including only significant predictors of GBD. According to this model, heritability for GBD was high (h2 = 0.44+/-0.18), after accounting for the significant effects of age, leptin in both sexes, total cholesterol, and HDL cholesterol in males only. We have shown quantitatively that variation in GBD is under strong genetic control. However, there are two major limitations to our findings: (1) since GBD was defined by a self-reported clinical history rather than an ultrasound examination, the prevalence of GBD could have been underestimated; and (2) since our design did not allow for shared environmental effects, our estimate of heritability may have been inflated.

Genetic admixture and gallbladder disease in Mexican Americans.

Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine the possibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans. This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans. Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations.

Increased gallbladder-related mortality among Hispanics: does education play a role?

OBJECTIVE: Hispanics, particularly Mexican Americans, are known to have a higher incidence of mortalities whose underlying cause is a gallbladder-related disorder. These analyses evaluate the role of educational attainment in the differential mortality experiences of these populations. METHODS: US mortality data for 1989-1991 were examined to determine ethnically-specific death rates using 'any mention' of the disease on the death certificate. RESULTS: Age-adjusted multiple cause mortality was found to be higher for all gallbladder-related disorders among Hispanics, particularly Mexican Americans. Mortality due to gallbladder cancer, gallstones and 'other gallbladder diseases' were found to be inversely proportional to educational attainment in all ethnic groups. When both age and education were used to adjust mortality, the gallstone and other gallbladder disease mortality among Hispanics was non-significantly higher than white, non-Hispanics. However, mortality due to gallbladder cancer remained significantly higher among Hispanics. CONCLUSION: Gallbladder cancer mortality is elevated in Hispanic populations, especially Mexican Americans, independent of educational attainment. However, increased mortality associated with gallstones or other gallbladder diseases among Hispanics may be partially due to differences in factors associated with educational attainment. Research and public health efforts to address these educational-related factors may improve this mortality pattern among Hispanics.

Food-frequency questionnaire validation among Mexican-Americans: Starr County, Texas.

A food-frequency questionnaire (FFQ) for low-income Mexican-Americans in Starr County, Texas, was developed as part of an epidemiologic study of gallbladder disease during 1985 and 1986. The FFQ was developed from 7-day food records collected from the first sample. In the validity study, using the second sample, correlations between nutrients calculated from 3-day food records and the FFQ were 0.77, 0.76, and 0.61 for energy, total fat, and saturated fat, respectively. In the reliability study, using the third sample, for the 1-month interval between baseline and a repeat FFQ measurement correlations ranged from 0.90 for energy to 0.85 for total fat and for the 2-month interval they were 0.84 for energy and 0.70 for total fat. The high correlations are largely explained by the lack of diversity in the diets of Starr County individuals which facilitated the high agreement between the FFQ and the food records for estimates of energy, fats, and cholesterol.

A comparison of three methods for assessing Amerindian admixture in Mexican Americans.

Epidemiologic studies have revealed that Mexican Americans experience an excess of non-insulin-dependent diabetes mellitus, gallbladder disease, and obesity relative to non-Hispanic whites. It has been hypothesized that the greater susceptibility of Mexican Americans to these disorders may be related to their greater degree of Amerindian genetic admixture. We evaluate the comparability of three different methods of assessing individual genetic admixture in Mexican Americans. Subjects were enrolled as part of the San Antonio Heart Study and were examined between 1979 and 1988 (n = 3301). Three different methods were used to assess Amerindian admixture: we queried subjects about their ancestors' ethnic origin, we measured subjects' skin color, and we estimated genetic admixture directly by analysis of polymorphic blood markers. These measures were generally poorly correlated with each other, with the highest correlations observed between skin color and proportion of Mexican-origin grandparents. In men, none of these three measures of genetic admixture was associated with the prevalence of diabetes, gallbladder disease, or obesity. In women, consistent positive associations were observed between admixture and all three diseases, regardless of the admixture measure used (ie, disease prevalence was higher among women with more Amerindian admixture). In both sexes, height was negatively correlated with all three measures of admixture, and admixture was also significantly correlated with body mass index and central adiposity in women. These data suggest that the three measures considered may assess different dimensions of admixture, but that for epidemiologic research, no one may be claimed to be superior to the others.

Prospective study of clinical gallbladder disease and its association with obesity, physical activity, and other factors.

The association of anthropometric measurements, serum tests, and life-style factors with the risk of clinical gallbladder disease was investigated in a prospective study of 7831 American men of Japanese ancestry in Hawaii. After 152,831 person-years of observation, 471 incident cases of gallbladder disease were diagnosed by histology or radiology. There was an increase in risk of gallbladder disease with a progressive increase in body mass index, height, pack-years of cigarette smoking, and diastolic blood pressure. There was a decrease in risk with an increase in physical activity, after controlling for the effect of other variables. There was also an inverse association with total caloric intake that could be related to dietary restriction in obese subjects or to the limitations of the 24-hr diet history. Serum cholesterol levels and the intake of total fat were not related to clinical gallbladder disease in this cohort.

Central adiposity and gallbladder disease in Mexican Americans.

Obesity is widely recognized as a risk factor for gallstones. However, to the authors' knowledge, only one study has examined the effect of body fat distribution on the prevalence of gallbladder disease. Mexican Americans are a population characterized by both a high prevalence of gallbladder disease and an unfavorable body fat distribution. The authors examined whether central adiposity (as measured by the ratio of subscapular-to-triceps skinfold) was related to clinically evident gallbladder disease in 1,202 Mexican Americans and 908 non-Hispanic whites in the San Antonio Heart Study from 1979 to 1982. After adjustment for overall adiposity (as measured by body mass index) and the ratio of subscapular-to-triceps skinfold, an increased prevalence of gallbladder disease was still observed in Mexican-American women. Both body mass index and the ratio of subscapular-to-triceps skinfold were positively and independently associated with gallbladder disease in women, while in men, body mass index, but not the subscapular-to-triceps skinfold ratio, was associated with gallbladder disease. Central adiposity is also related to the adverse pattern of cardiovascular risk factors observed in women with gallbladder disease.