Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study.

Background: In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Methods: Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18-55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18-55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18-55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. Findings: All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18-55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58-29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71-46.95) (anti-B.1.351); and for BiV, 14.39 (11.39-18.28) (anti-D614G) and 34.18 (25.84-45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. Interpretation: CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Funding: Sanofi and Biomedical Advanced Research and Development Authority (BARDA).

Genetics of Smoking Behaviors in American Indians.

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs. METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in the Northern Plains (n = 323) and the other in the Southwest (n = 176). A total of 384 SNPs were genotyped using an Illumina custom GoldenGate platform. Samples were also assessed for cotinine and 3-hydroxycotinine as markers of nicotine intake and nicotine metabolite ratio. RESULTS: Among 499 participants, we identified, in the Northern Plains sample only, a variant of the gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2) (rs2119767) on chromosome 4p that was associated with many of the intake biomarkers of smoking we examined, suggesting a role for this gene in modifying smoking behavior in this population. We also identified three SNPs, in the Southwest sample only, as significant correlates of only cigarettes per day: rs4274224, rs4245147 (both dopamine receptor D2 gene), and rs1386493 (tryptophan hydroxylase 2 gene). CONCLUSIONS: The contribution of many genes known to underlie smoking behaviors in NHWs may differ in AIs. IMPACT: Once validated, these variants could be useful in developing more effective cessation strategies.

Active smoking, secondhand smoke exposure and serum cotinine levels among Cheyenne River Sioux communities in context of a Tribal Public Health Policy.

INTRODUCTION: American Indians and Alaska Natives face disproportionately high rates of smoking and secondhand smoke (SHS) exposure. The Cheyenne River Sioux Tribe (CRST) is among the few Tribal Nations controlling commercial tobacco exposures in public and work places. We had an opportunity to explore effects of the new commercial tobacco-free policy (implemented in 2015) in an environmental health study (2014-2016) that collected information about commercial tobacco use and SHS prevalence and examined predictor variables of serum cotinine concentrations. METHODS: Self-reported survey data were used in quantile regression statistical modelling to explore changes in cotinine levels, based on smoking status, smokeless tobacco consumption and SHS exposure. RESULTS: From enrolled 225 adults, 51% (N=114) were current smokers. Among 88 non-tobacco users, 35 (40%) reported current SHS exposure. Significant differences in cotinine median concentrations were found among participants with and without current SHS exposure. Extremely high cotinine concentrations (~100 times larger than the median) were detected in some non-tobacco users. After implementing the new smoke-free air Tribal policy, cotinine decreased in participants with intermediate (3-15 ng/mL, non-tobacco users with SHS exposure) and high (>15 ng/mL, mainly tobacco users) cotinine levels showing association with an abatement of opportunities for SHS exposure. Significant predictors of cotinine levels were sampling year, current smoking and tobacco chewing. No gender differences were observed in cotinine. CONCLUSIONS: Our results show decrease in cotinine concentrations in CRST participants since implementation of their 'Smoke-Free Clean Air Act' in 2015.

Relationships Between Smoking Behaviors and Cotinine Levels Among Two American Indian Populations With Distinct Smoking Patterns.

Introduction: Smoking prevalence, cigarettes per day (CPD), and lung cancer incidence differ between Northern Plains (NP) and Southwest (SW) American Indian populations. We used cotinine as a biomarker of tobacco smoke exposure to biochemically characterize NP and SW smokers and nonsmokers and to investigate factors associated with variation in tobacco exposure. Methods: American Indians (N = 636) were recruited from two different tribal populations (NP and SW) as part of a study conducted as part of the Collaborative to Improve Native Cancer Outcomes P50 project. For each participant, a questionnaire assessed smoking status, CPD, second-hand smoke exposure, and traditional ceremonial tobacco use; plasma and/or salivary cotinine was measured. Results: Cotinine levels were (mean ± 95% confidence interval [CI]) 81.6 ± 14.1 and 21.3 ± 7.3 ng/ml among NP smokers and non-mokers, respectively, and 44.8 ± 14.4 and 9.8 ± 5.8 ng/ml among SW smokers and nonsmokers, respectively. Cotinine levels correlated with CPD in both populations (p < .0001). Cotinine ≥15 ng/ml was measured in 73.4% of NP smokers and 47.8% of SW smokers and in 19.0% of NP nonsmokers and 10.9% of SW nonsmokers. Ceremonial traditional tobacco use was associated with higher cotinine among NP smokers only (p = 0.004). Second-hand smoke exposure was associated with higher cotinine among NP non-smokers (P < 0.02). More secondhand smoke exposure was associated with smoking more CPD in both populations (p = 0.03-0.29). Linear regression modeling mirrored these findings. Conclusions: High prevalence of smoking in the Northern Plains and high cotinine levels among nonsmokers in both regions highlights the tribal populations' risk for tobacco-related disease. Implications: There is a high prevalence of smoking in Northern Plains American Indians. Among Northern Plains and Southwest nonsmokers, relatively high cotinine levels, representative of high tobacco exposure, suggest considerable exposure to second-hand smoke. It is critical to highlight the extent of second-hand smoke exposure among the Northern Plains and Southwest American Indians and to enhance efforts to initiate smoke-free policies in tribal communities, which are not subject to state-level polices.

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer.

OBJECTIVE: The Northern Plains (NP) and Southwest (SW) American Indian populations differ in their smoking patterns and lung cancer incidence. We aimed to compare CYP2A6 genetic variation and CYP2A6 enzyme activity (representative of the rate of nicotine metabolism) between the two tribal populations as these have previously been associated with differences in smoking, quitting, and lung cancer risk. PARTICIPANTS AND METHODS: American Indians (N=636) were recruited from two different tribal populations (NP in South Dakota, SW in Arizona) as part of a study carried out as part of the Collaborative to Improve Native Cancer Outcomes P50 Project. A questionnaire assessed smoking-related traits and demographics. Participants were genotyped for CYP2A6 genetic variants *1B, *2, *4, *7, *9, *12, *17, and *35. Plasma and/or saliva samples were used to measure nicotine's metabolites cotinine and 3'-hydroxycotinine and determine CYP2A6 activity (3'-hydroxycotinine/cotinine, i.e. the nicotine metabolite ratio, NMR). RESULTS: The overall frequency of genetically reduced nicotine metabolizers, those with CYP2A6 decrease-of-function or loss-of-function alleles, was lower in the NP compared with the SW (P=0.0006). The CYP2A6 genotype was associated with NMR in both tribal groups (NP, P<0.0001; SW, P=0.04). Notably, the rate of nicotine metabolism was higher in NP compared with SW smokers (P=0.03), and in comparison with other ethnic groups in the USA. Of the variables studied, the CYP2A6 genotype was the only variable to significantly independently influence NMR among smokers in both tribal populations (NP, P<0.001; SW, P=0.05). CONCLUSION: Unique CYP2A6 allelic patterns and rates of nicotine metabolism among these American Indian populations suggest different risks for smoking, and tobacco-related disease.

Using Genetic Technologies To Reduce, Rather Than Widen, Health Disparities.

Evidence shows that both biological and nonbiological factors contribute to health disparities. Genetics, in particular, plays a part in how common diseases manifest themselves. Today, unprecedented advances in genetically based diagnoses and treatments provide opportunities for personalized medicine. However, disadvantaged groups may lack access to these advances, and treatments based on research on non-Hispanic whites might not be generalizable to members of minority groups. Unless genetic technologies become universally accessible, existing disparities could be widened. Addressing this issue will require integrated strategies, including expanding genetic research, improving genetic literacy, and enhancing access to genetic technologies among minority populations in a way that avoids harms such as stigmatization.

Evaluating disparities in inpatient surgical cancer care among American Indian/Alaska Native patients.

BACKGROUND: American Indian/Alaska Native (AI/AN) patients with cancer have the lowest survival rates of all racial and ethnic groups, possibly because they are less likely to receive "best practice" surgical care than patients of other races. METHODS: Prospective cohort study comparing adherence with generic and cancer-specific guidelines on processes of surgical care between AI/AN and non-Hispanic white (NHW) patients in Washington State (2010 to 2014) was conducted. RESULTS: A total of 156 AI/AN and 6,030 NHW patients underwent operations for 10 different cancers, and had similar mean adherence to generic surgical guidelines (91.5% vs 91.9%, P = .57). AI/AN patients with breast cancer less frequently received preoperative diagnostic core needle biopsy (81% vs 94%, P = .004). AI/AN patients also less frequently received care adherent to prostate cancer-specific guidelines (74% vs 92%, P = .001). CONCLUSION: Although AI/ANs undergoing cancer operations in Washington receive similar overall best practice surgical cancer care to NHW patients, there remain important, modifiable disparities that may contribute to their lower survival.

Strengthening breast and cervical cancer control through partnerships: American Indian and Alaska Native Women and the National Breast and Cervical Cancer Early Detection Program.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has played a critical role in providing cancer screening services to American Indian and Alaska Native (AI/ANs) women and strengthening tribal screening capacity. Since 1991, the NBCCEDP has funded states, tribal nations, and tribal organizations to develop and implement organized screening programs. The ultimate goal is to deliver breast and cervical cancer screening to women who do not have health insurance and cannot afford to pay for these services. The delivery of clinical services is supported through complementary program efforts such as professional development, public education and outreach, and patient navigation. This article seeks to describe the growth of NBCCEDP's tribal commitment and the unique history and aspects of serving the AI/AN population. The article describes: 1) how this program has demonstrated success in improving screening of AI/AN women; 2) innovative partnerships with the Indian Health Service, state programs, and other organizations that have improved tribal public health infrastructure; and 3) the evolution of Centers for Disease Control and Prevention work with tribal communities.

Prostate cancer deaths and incident cases among American Indian/Alaska Native men, 1999-2009.

OBJECTIVES: We linked databases to improve identification of American Indians/Alaska Natives (AI/ANs) in determining prostate cancer death and incidence rates. METHODS: We linked prostate cancer mortality and incidence data with Indian Health Service (IHS) patient records; analyses focused on residents of IHS Contract Health Service Delivery Area (CHSDA) counties. We calculated age-adjusted incidence and death rates for AI/AN and White men for 1999 to 2009; men of Hispanic origin were excluded. RESULTS: Prostate cancer death rates were higher for AI/AN men than for White men. Death rates declined for White men (-3.0% per year) but not for AI/AN men. AI/AN men had lower prostate cancer incidence rates than White men. Incidence rates declined among Whites (-2.2% per year) and AI/ANs (-1.9% per year). CONCLUSIONS: AI/AN men had higher prostate cancer death rates and lower prostate cancer incidence rates than White men. Disparities in accessing health care could contribute to mortality differences, and incidence differences could be related to lower prostate-specific antigen testing rates among AI/AN men.

Design of a randomized controlled trial of a web-based intervention to reduce cardiovascular disease risk factors among remote reservation-dwelling American Indian adults with type 2 diabetes.

We describe a randomized controlled trial, the Lakota Oyate Wicozani Pi Kte (LOWPK) trial, which was designed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease (CVD) among a group of remote reservation-dwelling adult American Indian men and women with type 2 diabetes who are at high risk for CVD. Enrollment on a rolling basis of 180 planned participants began during 2009; an average 18-month follow-up was completed by June 2011. The primary outcome variable is change in glycosylated hemoglobin level after an average 18-month follow-up period. Secondary outcome variables include changes in low-density lipoprotein cholesterol, systolic blood pressure, body mass index, and smoking status, as well as an evaluation of intervention cost-effectiveness. If effective, the LOWPK trial may serve as a guide for future chronic disease intervention trials in remote, technologically challenged settings.

Community-responsive interventions to reduce cardiovascular risk in American Indians.

American Indian and Alaska Native (AI/AN) populations bear a heavy burden of cardiovascular disease (CVD), and they have the highest rates of risk factors for CVD, such as cigarette smoking, obesity, and diabetes, of any U.S. population group. Yet, few randomized controlled trials have been launched to test potential preventive interventions in Indian Country. Five randomized controlled trials were initiated recently in AI/AN communities to test the effectiveness of interventions targeting adults and/or children to promote healthy behaviors that are known to impact biological CVD risk factors. This article provides a context for and an overview of these five trials. The high burden of CVD among AI/AN populations will worsen unless behaviors and lifestyles affecting CVD risk can be modified. These five trials, if successful, represent a starting point in addressing these significant health disparities.

Physical activity and cervical cancer testing among American Indian women.

PURPOSE: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervical cancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated with screening adherence among AI women from 2 culturally distinct regions in the Northern Plains and the Southwest. METHODS: A total of 1,979 AI women at least 18 years of age participating in a cross-sectional cohort study reported whether they received a Pap test within the previous 3 years. Physical activity level was expressed as total metabolic equivalent (MET) scores and grouped into quartiles. We used binary logistic regression to model the association of Pap testing and MET quartile, adjusting for demographic and health factors. FINDINGS: Overall, 60% of women received a Pap test within the previous 3 years. After controlling for covariates, increased physical activity was associated with higher odds of Pap screening (OR = 1.1 per increase in MET quartile; 95% CI = 1.1, 1.2). CONCLUSIONS: This is the first study to examine physical activity patterns and receipt of cancer screening in AIs. While recent Pap testing was more common among physically active AI women, prevalence was still quite low in all subgroups. Efforts are needed to increase awareness of the importance of cervical cancer screening among AI women.

A gene-family analysis of 61 genetic variants in the nicotinic acetylcholine receptor genes for insulin resistance and type 2 diabetes in American Indians.

Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with smoking phenotypes and are likely to influence diabetes. Although each single variant may have only a minor effect, the joint contribution of multiple single nucleotide polymorphisms (SNPs) to the occurrence of disease may be larger. In this study, we conducted a gene-family analysis to investigate the joint impact of 61 tag SNPs in 7 nAChRs genes on insulin resistance and type 2 diabetes in 3,665 American Indians recruited by the Strong Heart Family Study. Results show that although multiple SNPs showed marginal individual association with insulin resistance and type 2 diabetes, only a few can pass adjustment for multiple testing. However, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant association of the nAChR gene family with both insulin resistance and type 2 diabetes (both P < 0.0001), suggesting that genetic variants in the nAChR genes jointly contribute to insulin resistance and type 2 diabetes among American Indians. The effects of these genetic variants on insulin resistance and diabetes are independent of cigarette smoking per se.

Impact of hysterectomy and bilateral oophorectomy prevalence on rates of cervical, uterine, and ovarian cancer among American Indian and Alaska Native women, 1999-2004.

OBJECTIVE: To present more accurate incidence rates of cervical, uterine, and ovarian cancer by geographic region in American Indian/Alaska Native (AI/AN) women. METHODS: The authors used data from central cancer registries linked to Indian Health Service (IHS) patient registration database, the Behavioral Risk Factor Surveillance System, IHS National Data Warehouse, and the National Hospital Discharge Survey. Cancer incidence rates were adjusted for hysterectomy and oophorectomy prevalence and presented by region for non-Hispanic White (NHW) and AI/AN women. RESULTS: AI/AN women had a higher prevalence of hysterectomy (23.1%) compared with NHW women (20.9%). Correcting cancer rates for population-at-risk significantly increased the cancer incidence rates among AI/AN women: 43% for cervical cancer, 67% for uterine cancer, and 37% for ovarian cancer. Risk-correction led to increased differences in cervical cancer incidence between AI/AN and NHW women in certain regions. CONCLUSIONS: Current reporting of cervical, uterine, and ovarian cancer underestimates the incidence in women at risk and can affect the measure of cancer disparities. Improved cancer surveillance using methodology to correct for population-at-risk may better inform disease control priorities for AI/AN populations.

Culture and colorectal cancer screening on three American Indian reservations.

BACKGROUND: Colorectal cancer (CRC) rates among many American Indian populations are high. Screening by fecal occult blood test (FOBT) and endoscopy is effective for reducing CRC mortality, but little research has examined the extent of such screening in reservation populations. Further, nothing is known of how American Indians' cultural characteristics may be related to screening receipt. PARTICIPANTS AND SETTING: We examined data from participants recruited from 2 Northern Plains and 1 Southwest reservation for the Education and Research Toward Health (EARTH) study. All participants aged > or = 51 years were eligible for inclusion. DESIGN: After calculating screening rates, we examined bivariate relationships between screening and participant characteristics, including measures of cultural characteristics including ethnic identity and use of traditional healing practices. We applied multivariate regression to relate these cultural variables to odds of lifetime screening by FOBT or endoscopy. RESULTS: Of 751 American Indians sampled, 35% reported lifetime CRC screening by at least one modality. Multivariate analyses did not reveal significant relationships or trends relating FOBT to respondents' cultural characteristics. By contrast, odds of endoscopy were significantly lower among persons who spoke a tribal language at home (OR .6, 95% C.I. .4-.9), and trend analysis revealed an inverse relationship between endoscopy and number of identity measures endorsed (Ptrend<.1). CONCLUSIONS: The sampled population exhibits disparities in CRC compared to the general population, and cultural characteristics are related to odds of endoscopy. Findings warrant culturally tailored CRC screening initiatives for American Indians.

Patterns of cigarette smoking initiation in two culturally distinct American Indian tribes.

OBJECTIVES: To better understand patterns of initiation among American Indians we examined age-related patterns of smoking initiation during adolescence and young adulthood in 2 American Indian tribes. METHODS: We used log-rank comparison and a Cox proportional hazard regression model to analyze data from a population-based study of Southwest and Northern Plains American Indians aged 18 to 95 years who initiated smoking by age 18 years or younger. RESULTS: The cumulative incidence of smoking initiation was much higher among the Northern Plains Indians (47%) than among the Southwest Indians (28%; P < .01). In the Southwest, men were more likely than women to initiate smoking at a younger age (P < .01); there was no such difference in the Northern Plains sample. Northern Plains men and women in more recent birth cohorts initiated smoking at an earlier age than did those born in older birth cohorts. Southwest men and women differed in the pattern of smoking initiation across birth cohorts as evidenced by the significant test for interaction (P = .01). CONCLUSION: Our findings underscore the need to implement tobacco prevention and control measures within American Indian communities.

Prostate cancer incidence among American Indian and Alaska Native men, US, 1999-2004.

BACKGROUND: American Indian and Alaska Native (AI/AN) men experience lower incidence of prostate cancer than other race/ethnic populations in the US, but racial misclassification of AI/AN men threatens the validity of these estimates. To the authors' knowledge, little is known concerning prostate-specific antigen (PSA) testing in AI/AN men. METHODS: The authors linked cancer registry data with Indian Health Service enrollment records to improve race classification. Analyses comparing cancer incidence rates and stage at diagnosis for AI/AN and non-Hispanic white (NHW) men for 6 geographic regions focused on counties known to have less race misclassification. The authors also used Behavioral Risk Factors Surveillance System data to characterize PSA testing in AI/AN men. RESULTS: Prostate cancer incidence rates were generally lower in AI/AN than in NHW men for all regions combined (rate ratio of 0.68). However, regional variation was noted among AI/AN men, with incidence rates (per 100,000 population) ranging from 65.7 in the Southwest to 174.5 on the Northern Plains. The rate of distant stage disease was somewhat higher among AI/AN (7.8) than NHW (6.2) men. Nationally, AI/AN men were less likely than NHW men to have undergone recent PSA testing (48.4% vs 58.0%), with prominent regional variation in screening rates noted. CONCLUSIONS: Prostate cancer incidence rates and the proportion of men with recent PSA testing were lower for AI/AN men than for NHW men. However, incident rates and rate of distant stage varied by region more for AI/AN than for NHW. Further research is needed among AI/AN men to evaluate strategies for better understanding the causes of the regional variation in prostate cancer incidence.

Gastric cancer among American Indians and Alaska Natives in the United States, 1999-2004.

BACKGROUND: Gastric cancer incidence rates for American Indians and Alaska Natives (AI/ANs) historically have exceeded those for non-Hispanic whites (NHWs). Previous reports may have underestimated the true burden of gastric cancer in AI/AN populations because of misclassification of AI/AN race in cancer registries. METHODS: Population-based cancer registry data from 1999 through 2004 were used to describe gastric cancer incidence in AI/ANs and NHWs in the US. To address misclassification of race, registry data were linked with Indian Health Service administrative records, and analyses were restricted to residents of Contract Health Service Delivery Areas (CHSDA). Disease patterns were assessed for 6 geographic regions and for all regions combined. Rates were expressed per 100,000 population and were age-adjusted to the 2000 US standard population. RESULTS: In CHSDA counties, gastric cancer incidence rates for AI/ANs were higher than the rates for NHWs across most regions. For both sexes combined, AI/AN rates ranged from 6.1 in the East region to 24.5 in Alaska; there was relatively little regional variation in NHW rates. Most patients with gastric cancer were diagnosed with late-stage disease, regardless of race, age, or sex. In some regions, cancer rates in the central/distal portions of the stomach were higher among AI/ANs than among NHWs, whereas rates in the proximal stomach were similar between the 2 populations. CONCLUSIONS: AI/ANs are generally at greater risk for gastric cancer than NHWs. Relatively high rates of cancer in the central/distal portions of the stomach among AI/ANs in some geographic regions may indicate a disproportional burden of Helicobacter pylori-associated disease.

Primary liver cancer incidence among American Indians and Alaska Natives, US, 1999-2004.

BACKGROUND: American Indians and Alaska Natives (AI/AN) experience higher morbidity and mortality from primary liver cancer than other United States (US) populations, but racial misclassification in medical records results in underestimates of disease burden. METHODS: To reduce misclassification, National Program of Cancer Registries and Surveillance, Epidemiology, and End Results data were linked with Indian Health Service (IHS) enrollment records to compare primary liver cancer incidence and stage at diagnosis between AI/AN and non-Hispanic whites (NHW) living within the regionalized IHS Contract Health Service Delivery Area counties. Incidence rates are expressed per 100,000 persons and age-adjusted by 19 age groups to the 2000 US standard population. RESULTS: Overall, AI/AN have a higher proportion of hepatocellular carcinoma compared with NHW, 77.8% versus 66.7%. Liver cancer incidence rates among AI/AN males and females were higher than those among NHW males and females for all regions except for the East. Among males, rates ranged from 7.3 (95% confidence interval [CI], 3.8-12.6) in the East to 17.2 (95% CI, 10.4-26.3) in Alaska. Among females, rates ranged from 3.8 (95% CI, 1.4-8.2) in the East to 6.9 (95% CI, 3.6-11.6) in Alaska. The AI/AN rates for all regions were consistently higher than the NHW rates at every age. An increasing trend among AI/AN was suggested but did not achieve statistical significance. CONCLUSIONS: Reducing racial misclassification revealed higher disparities in primary liver cancer incidence between NHW and AI/AN populations than previously reported. Further description of the reasons for regional differences in this disparity is needed, as are programs to reduce risk factors and to diagnose primary liver cancer at earlier, more treatable stages.