Safety behaviours among Alaskan Native and American Indian people living in Alaska.

OBJECTIVE: To examine self-reported safety behaviours among 3828 Alaskan Native and American Indian people enrolled in the Alaska Education and Research Towards Health (EARTH) Study, 2004-2006. DESIGN: A cross-sectional analysis of baseline data from a cohort study. A non-random sample of participants (2322 women and 1506 men) aged > or =18 years from three regions of Alaska completed questions on safety behaviours as part of a comprehensive health and lifestyle computer-assisted self-administered questionnaire. RESULTS: Most participants reported never driving after drinking (94.1%) or riding with a driver who had been drinking (91.3%). Fewer (74.1%) participants reported using a seatbelt always or almost always when riding in a vehicle. Only about half (55%) always kept to the speed limit when driving or used a personal flotation device when boating (51.5%). Even fewer (20.5%) reported using a helmet when riding on off-road vehicles, including four-wheelers and snowmobiles. Factors identified among those least likely to use safety devices and practise good safety behaviours are: younger age, lower household income and education, non-married, speaking only English at home, and a self-reported health status of poor to fair (p<0.05). CONCLUSIONS: Recommendations for future injury prevention efforts in this population are to increase use of personal flotation devices while boating and address the underuse of helmets with off-road vehicles. Limited prevention resources should be used to target those who engage in risky behaviours to maximise programme impact.

Antibody responses of variable lymphocyte receptors in the lamprey.

Lamprey and hagfish, the living representatives of jawless vertebrates, use genomic leucine-rich-repeat cassettes for the combinatorial assembly of diverse antigen receptor genes encoding variable lymphocyte receptors of two types: VLRA and VLRB. We describe here the VLRB-bearing lineage of lymphocytes in sea lamprey. These cells responded to repetitive carbohydrate or protein determinants on bacteria or mammalian cells with lymphoblastoid transformation, proliferation and differentiation into plasmacytes that secreted multimeric antigen-specific VLRB antibodies. Lacking a thymus and the ability to respond to soluble protein antigens, lampreys seem to have evolved a B cell-like system for adaptive humoral responses.

Resequencing of the human major histocompatibility complex in patients with rheumatoid arthritis and healthy controls in Alaska Natives of Southeast Alaska.

High prevalence and severity of rheumatoid arthritis (RA) with an early age of onset have previously been described in Alaska Native and American Indian (AN/AI) populations. The contribution of HLA-DRB1 alleles encoding a similar amino acid sequence, referred to as the shared epitope (SE), to RA risk is well recognized in multiple populations worldwide. DRB1*1402 allele is the major SE-encoding allele in AN/AI populations. However, DRB1*1402 is highly prevalent in healthy Alaska Natives of Southeast Alaska (AN), with no significant difference from RA patients, indicating this allele alone is not informative for defining genetic risk and non-human leukocyte antigen (non-HLA) genes are likely important in AN. We sought to deep resequence the human major histocompatibility complex (MHC) to characterize the single-nucleotide polymorphism (SNP) haplotypes within this region in RA cases and controls in AN. Approximately 99 kb of the MHC was resequenced with 95 amplicons throughout this region. Thirty-four cases and 74 controls were examined. A total of 696 SNPs were discovered from 85 of the selected 95 amplicons. Disease association signals were detected for nine of the 95 amplicons analyzed. Increased risk of RA was associated with five amplicons in the class I, class II or class III region and resistance to disease with four amplicons in the class I region. Our results indicate that non-HLA MHC genes and/or unknown exogenous factors likely modulate risk of RA in the AN population.

A prospective cohort of American Indian and Alaska Native people: study design, methods, and implementation.

In 2001, the National Cancer Institute funded three centers to test the feasibility of establishing a cohort of American Indian and Alaska Native people. Participating tribal organizations named the study EARTH (Education and Research Towards Health). This paper describes the study methods. A computerized data collection and tracking system was developed using audio computer-assisted survey methodology with touch screens. Data were collected on diet, physical activity, lifestyle and cultural practices, medical and reproductive history, and family history of heart disease, diabetes, and cancer. In addition, a small panel of medical measurements was obtained, including height, weight, waist and hip circumferences, blood pressure, and a lipid panel plus glucose. At the completion of the enrollment visit, data were used to provide immediate health feedback to study participants. During the initial funding period, the authors anticipate enrolling 16,000 American Indian and Alaska Native participants. The age distribution of the study population was similar to that reported in the 2000 US Census for the relevant populations. A component critical to the success of the EARTH Study has been the partnerships with tribal members. The study has focused on involvement of American Indian and Alaska Native communities in development and implementation and on provision of feedback to participants and communities.

FcRH1: an activation coreceptor on human B cells.

B-cell activation and differentiation is regulated through the coordinated function of a dynamic array of cell surface receptors. At different stages in their differentiation, human B cells may express one or more members of a large family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential. Among these newly identified transmembrane molecules, FcRH1 is unique in having 2 immunoreceptor tyrosine-based activation motif (ITAM)-like motifs in its intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1 antibodies and mRNA analysis to evaluate FcRH1 expression and function during B-cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels on naive B cells, and is down-regulated after B cells are activated to begin to form germinal centers. This FcRH1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry, and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)-induced Ca(2+) mobilization and proliferation. FcRH1 thus has the potential to serve as an activating coreceptor on B cells.

Diabetes among Alaska Natives: a review.

This review summarizes the published information on diabetes mellitus and gestational diabetes among Alaska Natives. The most recently published age-adjusted prevalence was 28.3/1000 in 1998. There is evidence of a steadily increasing prevalence, documented both by cross sectional screening studies and patient registry methods. The overall incidence rates in 1986-1998 of lower extremity amputation (6.1/1000) and renal replacement therapy (2.1/1000) appear to be lower than those in other Native American populations in the United States. Incidence of stroke and MI in 1986-1998 varied widely by ethnic group and gender with Eskimo women having the highest rate of stroke (19.6/1000), and Aleut men the highest rate of MI (14/1000). The overall mortality among diabetic Alaska Native people in 1986-1993 (43.2/1000) was somewhat lower than that in other US diabetic populations, with heart disease being the most common cause of death. A high rate of gestational diabetes (6.7%) was reported in one region in 1987-88, but this appeared to decline following nutritional education intervention. In screening studies, the prevalence of abnormal glucose tolerance has been found to be positively associated with body mass index and negatively associated with daily seal oil or salmon consumption and higher levels of physical activity. Observations on the prevalence and relationships among other factors in the insulin resistance syndrome are summarized. Suggestions for prevention of diabetes and further studies are presented.

Isolation and characterization of lymphocyte-like cells from a lamprey.

Lymphocyte-like cells in the intestine of the sea lamprey, Petromyzon marinus, were isolated by flow cytometry under light-scatter conditions used for the purification of mouse intestinal lymphocytes. The purified lamprey cells were morphologically indistinguishable from mammalian lymphocytes. A cDNA library was prepared from the lamprey lymphocyte-like cells, and more than 8,000 randomly selected clones were sequenced. Homology searches comparing these ESTs with sequences deposited in the databases led to the identification of numerous genes homologous to those predominantly or characteristically expressed in mammalian lymphocytes, which included genes controlling lymphopoiesis, intracellular signaling, proliferation, migration, and involvement of lymphocytes in innate immune responses. Genes closely related to those that in gnathostomes control antigen processing and transport of antigenic peptides could be ascertained, although no sequences with significant similarity to MHC, T cell receptor, or Ig genes were found. The data suggest that the evolution of lymphocytes in the lamprey has reached a stage poised for the emergence of adaptive immunity.

Cancer mortality among Alaska natives, 1994-1998.

Although overall cancer mortality rates in the U.S. declined throughout the 1990s, Alaska Native rates increased. This study compares mortality patterns of Alaska Natives for the period, 1994-1998, and U.S. Whites, and examines changes in rates since 1960-1969. We used death certificate data and Indian Health Service population estimates to create age-adjusted mortality rates for Alaska Natives. We compared these rates to NCHS mortality for U.S. Whites. In all, 597 Alaska Natives died of cancer over the five-year period, 1994-1998, their age-adjusted average annual mortality rate (224.5 per 100,000) was thirty percent higher than that of U.S. Whites (166.7 per 100,000), a statistically significant excess (OR = 1.3, 95% CI: 1.2-1.4). Alaska Natives were forty percent more likely to die of lung cancer than U.S. Whites (OR = 1.4, 95% CI: 1.2-1.6). This population also demonstrated elevated mortality rates for several other smoking-related cancers. Also, Alaska Natives are at excess risk for nearly all cancers of the digestive system. Alaska Natives experienced the same or lower mortality rates for genitourinary cancers excluding cancer of the kidney. Smoking related cancers, and particularly, lung cancer, were the major contributors to the excess mortality rates. These data suggest that the burden of cancer on the Alaska Native healthcare system will continue to increase as the population ages. Intensified efforts to modify behavioral risk factors are needed.

Dietary intake among Alaska native women resident of Anchorage, Alaska.

OBJECTIVE: We summarized data from a study of Alaska Native women living in predominantly urban communities to assess the quality of their dietary intakes and compare to current US dietary recommendations. STUDY DESIGN: Descriptive cross sectional study of seventy-four Alaska Native women living in and around Anchorage, Alaska. Each completed up to four 24-h diet recalls during one year. Participants were enrolled in 1996 and 1997. Blood samples were analyzed for hematocrit, vitamin A, vitamin C, vitamin E and folate. RESULTS: Results were compared with current US dietary guide lines for food groups and nutrients. Mean intake of these women fell below recommendations for all food groups except the Meat and Beans Group. Mean intakes of sweets, sodium and energy from fat and saturated fat exceeded recommendations. Red blood cell folate levels were low in 32% of the women. Only one-quarter of the women reported eating Native foods. CONCLUSIONS: The survey shows room for improvement in diet to include reduced intakes of saturated fat, and increased intakes of folate, calcium, and dietary fiber by increasing consumption of fruits and vegetables, whole grain breads and cereals, non-fat milk products, and Native foods.

Exposure to persistent organochlorines among Alaska Native women.

OBJECTIVES: To report the levels of DDT, DDE, other chlorinated pesticides, and PCBs found in 131 Alaska Native women who had serum samples collected between 1980 and 1987 and to compare these levels to other published studies of DDE and PCB exposure among U.S. women. STUDY DESIGN: Review of data collected during a case-control study of the relationship between organochlorine chemicals and breast cancer. Data for case and control women were pooled in this analysis because case-control differences were found to be minimal and because serum samples pre-dated cancer diagnoses by 3 to 10 years. RESULTS: More than 99% of the women had detectable levels of p,p-DDE (mean 9.10 ng/mL or ppb). Mean total PCB level was 7.56 ppb. Levels of exposure varied by geographical location and ethnic identification, which maybe a reflection of dietary differences. Five of the organochlorines were detected in at least half of the study population. Results were recalculated using detection limits corresponding to other published studies of DDE and PCB levels in U.S. women. Alaska women had levels similar to those reported from New York women collected in the 1980s. We compared the PCB congener levels measured in Alaska Native women with levels reported in Arctic animals and found similar PCB congener profiles. The six most frequently detected contaminants in Alaska Natives were also detected in the marine mammal samples reported by Becker et al (5). CONCLUSIONS: Our study identified widespread Alaska Native exposure to organochlorines that originated outside of the Arctic, a finding also seen in other studies. Our results provide a reference baseline for exposure levels during the 1980s, but further research is necessary to assess temporal trends in exposure among Alaska Natives. Further, the need for national and international inter-laboratory standardization for testing for persistent organochlorines to facilitate comparisons between Alaska Natives and other American populations is clearly demonstrated.

Cancer incidence in Alaska Natives thirty-year report 1969-1998.

The Alaska Native Tumor Registry includes data from 1969 to the present. This report provides incidence rates over the thirty year period, 1969 through 1998, and compares trends over time for Alaska Natives (AN) with those of US Whites and Blacks. To examine current rates, average annual age-adjusted incidence rates for AN for 1984-98 are compared with US Whites. Data from the registry document numerous differences in rates of occurrence of specific cancers compared to US Whites and Blacks. Studies of these differences may provide clues to the causes and risk factors for the cancers. Most importantly, these data show that although cancer was considered a rare disease in the Alaska Native population as recently as the mid-twentieth century, the incidence rate for all cancers combined among Alaska Natives is now as high as that of US Whites, and even higher in women. On the other hand, despite relative differences in rates, the most frequently diagnosed cancers among Alaska Natives are the same as US Whites. Cancers of the lung, colon/rectum, breast, and prostate are most frequently diagnosed among Alaska Natives and in the U.S. These four cancers comprise over 50% of all diagnosed invasive cancers. Cancer of the lung is almost entirely preventable by eradication of tobacco use. Screening and early detection have been proven to reduce mortality for cancers of the colon/rectum and breast. Primary and secondary prevention of these cancers could markedly improve morbidity and mortality.

Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study.

The benefits of screening hepatitis B surface antigen (HBsAg)-positive carriers for hepatocellular carcinoma (HCC) in terms of long-term survival have not been established. We conducted a prospective 16-year, population-based cohort study to determine the impact of screening for HCC in 1,487 HBsAg-positive Alaska native carriers with alpha-fetoprotein (AFP) determinations every 6 months. Men and nonpregnant women with an elevated AFP level were evaluated for the presence of HCC by ultrasound (US) examination. The long-term survival rate for patients whose HCC was detected by the screening program was compared with a historical control group of Alaska native patients with HCC from the same population who were clinically diagnosed with HCC between 1969 and October 1982, through a National Cancer Institute-sponsored Cancer Registry. Between October 1982 and December 1998, 26,752 AFP determinations in HBsAg carriers were performed. One or more AFP elevations were found in 61 men and 39 nonpregnant women. HCC was diagnosed in 32 patients (24 men and 8 women). HCC tumors less than 6 cm were found in 23 patients; 22 patients had resections, and 1 patient refused a resection. Compared with 12 patients with hepatitis B virus (HBV)-related HCC diagnosed from 1969 to October 1982, before this program, the 5- and 10-year survival rate for the 32 patients with HCC were 42% (P =.008) and 30% (P =.07), respectively. Five- and 10-year tumor-free survival rates for carriers who had a normal AFP level on initial screening and subsequently developed HCC were 29% (P =.004) and 24% (P =.024), respectively. Screening of HBsAg carriers with semiannual AFP was effective in detecting most HCC tumors at a resectable stage and significantly prolonged survival rates when compared with historical controls in this population.

Hepatocellular carcinoma not related to hepatitis B virus infection among Alaska natives.

Chronic infection with hepatitis B or C viruses is a common underlying condition in patients with hepatocellular carcinoma worldwide. We studied serum and liver tissue from a cohort of Alaska natives with hepatocellular carcinoma (HCC) for evidence of hepatitis B, C and G viral infection using conventional serological tests as well as the sensitive polymerase chain reaction. Evidence of HBV infection was found in 25 and possible HCV infection in two cases. Among the remaining 11 patients, four had a history of recent or remote alcoholism while seven had no recognizable risk factors for HCC. Only one was seropositive for HGV RNA and that was an individual with a history of alcoholism. Non-tumorous liver tissue was available for study in six of these seven cases. Histological features of chronic hepatitis were present in five. Thus, at least five of 38 (13%) Alaska natives with HCC appeared to have chronic hepatitis not related to HBV or HCV infection, suggesting the possibility of some form of previously unrecognized chronic liver disease predisposing to HCC.

Pap prevalence and cervical cancer prevention among Alaska Native women.

The goals of the Alaska Native Women's Health Project (WHP) were to determine the following: (1) Pap prevalence based on chart review before and during an intervention period; (2) the level of understanding of cancer and cancer screening services with emphasis on cervical cancer; (3) use and satisfaction with current health maintenance services; and (4) improvement in knowledge and cancer screening rates following intervention. A random sample of 481 Alaska Native (Eskimo, Aleut, Indian) women living in Anchorage were interviewed face to face about their understanding of cancer risk factors (tobacco use, sexually transmitted diseases (STDs), reproductive issues), cancer screening examinations (Pap test, breast self-examination (BSE), breast exam by a provider, mammography), and their attitudes about health care and health care services. Sixty-two percent of control women were documented to have had at least one Pap test within the 3-year period prior to the beginning of the study; however, only 9% were documented to have had annual Pap screening. The intervention included distribution of educational materials, counseling on any woman's health issue, special evening clinics, and reminders (mail/phone call) of scheduled Pap appointments.

Risk factors for cervical intraepithelial neoplasm in Alaska Native women: a pilot study.

Although rates for invasive cervical cancer have declined over the past twenty years among Alaska Native women, they continue to show high rates of pre-invasive cervical lesions (cervical intraepithelial neoplasia, or CIN). We investigated risk factors for CIN II/III among Alaska Native women in a pilot case-control study. Cases (n = 26) included women with biopsy-proven CIN II/III, while controls (n = 52) had normal cervical epithelium. The strongest risks associated with CIN II/III were HPV infection of any type (Crude Odds Ratio [OR] 8.4, 95% Confidence Interval [CI]: 2.9-29.4), HPV 16 infection (OR 40.8, 95% CI: 9.4-176.4), and a family history of cervical dysplasia (OR 3.9, 95% CI: 1.3-11.3). We also found that use of depot-medroxy progesterone acetate was associated with CIN (OR 3.0, 95% CI: 1.1-8.5). A larger investigation would be necessary to allow adequate evaluation of these, and other, risk factors for CIN among Alaska Native women.

Colorectal cancer incidence and survival among Alaska Natives, 1969-1993.

BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined. METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington. RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend towards improvement over time. CONCLUSIONS: Alaska Natives had substantially higher colorectal cancer incidence rates compared to western Washington whites. Rates were particularly high for Aleut and Eskimo women. These data suggest a need for intensified secondary prevention strategies for this high-risk population, while further research is needed to identify modifiable risk factors.

Dietary intakes among Siberian Yupiks of Alaska and implications for cardiovascular disease.

We describe dietary intake for 65 Siberian Yupik residents of Gambell, AK using 24-h recalls and annual food frequencies collected in October 1992. The objectives were to describe dietary characteristics important in risk of cardiovascular disease, determine the extent that their diet differs from the diet of general US and northern populations, assess how the diet met national guidelines for the prevention of cardiovascular disease, and propose dietary recommendations. Compared to US intakes in general (NHANES III), intakes of Siberian Yupiks expressed as percent of energy were: 8-10% higher in fat, 6% higher in protein, 5-7% higher in monounsaturated fats and 12-15% lower in carbohydrate. Energy from saturated and polyunsaturated fats was similar (11% and 8% respectively). Cholesterol intakes were not significantly different. Mean intakes of selenium, a-topocopherol, folacin (men), and vitamin C (men) met Recommended Dietary Allowances, which may contribute to cardiovascular health. Mean intake of n-3 fatty acids (7.0 g/d), twice the 3 g/d associated with favorable effects, was comparable with intake of Greenlandic Eskimos. Dietary risk factors included high intakes of % energy from fat and saturated fat, and low intakes of fiber. Native foods were important sources of monounsaturated fats, n-3 fatty acids and selenium.

Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population.

Hepatitis B virus (HBV) is major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. Serologic surveys performed in the 1970s and 1980s have demonstrated that Alaskan Eskimos, Canadian Inuit, and Greenland Inuit have very high prevalence rates of HBV. In Alaska, a high incidence of HCC in Eskimos, especially males, has been reported. Alaska Natives chronically infected with HBV have a relative risk of HCC of 148 compared to Alaska Natives who are not chronically infected. In Canada the incidence of HCC is six times more frequent in elderly Inuit than in Canadians in general. However, an elevated rate of HCC has not been found in Greenland. Primary prevention programs to prevent HCC by vaccination against HBV are being conducted in Alaska, Canada, and Greenland. In addition, in Alaska a program to detect HCC earlier by screening persons chronically infected with HBV, using semiannual alpha-fetoprotein testing, has resulted in detecting over 60% of HCC early enough for surgical resection.