Regional cancer control in south-eastern Nigeria: a proposal emanating from a UICC-sponsored workshop.

There is an impending cancer epidemic in Africa. In Nigeria, this disease is causing untold devastation, and control measures are desperately needed. Breast, cervical, prostate, and liver cancers are the most common types in Nigerian adults. In children, the predominant malignant diseases are Burkitt's lymphoma, acute lymphoblastic leukemia, neuroblastoma, and Wilm's tumor (nephroblastoma). The focus of efforts to control cancer in Nigeria should be directed at prevention with adequate attention to planning/policy making, early detection, accurate diagnosis, treatment and palliative care. National and regional allocation of sufficient resources is required, accompanied by measurable objectives and appropriate emphasis on accountability.

Childhood leukaemia in Belarus, Russia, and Ukraine following the Chernobyl power station accident: results from an international collaborative population-based case-control study.

BACKGROUND: There is little evidence regarding the risk of leukaemia in children following exposure to radionuclides from the Chernobyl Nuclear Power Plant explosion on April 26, 1986. METHODS: This population-based case-control study investigated whether acute leukaemia is increased among children who were in utero or <6 years of age at the time of the Chernobyl accident. Confirmed cases of leukaemia diagnosed from April 26, 1986 through December 31, 2000 in contaminated regions of Belarus, Russia, and Ukraine were included. Two controls were matched to each case on sex, birth year, and residence. Accumulated absorbed radiation dose to the bone marrow was estimated for each subject. RESULTS: Median estimated radiation doses of participants were <10 mGy. A significant increase in leukaemia risk with increasing radiation dose to the bone marrow was found. This association was most evident in Ukraine, apparent (but not statistically significant) in Belarus, and not found in Russia. CONCLUSION: Taken at face value, these findings suggest that prolonged exposure to very low radiation doses may increase leukaemia risk as much as or even more than acute exposure. However the large and statistically significant dose-response might be accounted for, at least in part, by an overestimate of risk in Ukraine. Therefore, we conclude this study provides no convincing evidence of an increased risk of childhood leukaemia as a result of exposure to Chernobyl radiation, since it is unclear whether the results are due to a true radiation-related excess, a sampling-derived bias in Ukraine, or some combination thereof. However, the lack of significant dose-responses in Belarus and Russia also cannot convincingly rule out the possibility of an increase in leukaemia risk at low dose levels.

Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk.

Polycyclic aromatic hydrocarbons, possible human breast carcinogens, are metabolized by cytochrome P4501A1 (CYP1A1) and glutathione S-transferase (GSTM1). A CYP1A1 polymorphism (isoleucine to valine substitution in exon 7) or the null allele for GSTM1 may affect the mutagenic potential of polycyclic aromatic hydrocarbons. We examined polymorphisms in GSTM1 and CYP1A1 in relation to breast cancer risk. Included were 216 postmenopausal Caucasian women with incident breast cancer and 282 community controls. DNA analyses suggested no increased breast cancer risk with the null GSTM1 genotype [odds ratio (OR) = 1.10; CI, 0.73-1.64], although there was some indication that the null genotype was associated with risk among the youngest postmenopausal women (OR = 2.44; CI, 0.89-6.64). Slightly elevated risk was associated with the CYP1A1 polymorphism (OR = 1.61; CI, 0.94-2.75) and was highest for those who smoked up to 29 pack-years (OR = 5.22; CI, 1.16-23.56). Statistical power to detect an effect may be limited by small numbers, and larger sample sizes would be required to corroborate these suggestive findings.

A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease.

There are several prognostic models for Hodgkin's disease (HD) patients, but none evaluating patient characteristics at time of blood and marrow transplantation (BMT). We developed a prognostic model for event-free survival (EFS) post-BMT based on HD patient characteristics measured at the time of autologous (auto) or allogeneic (allo) BMT. Between 1/1991 and 12/2001, 64 relapsed or refractory HD patients received an auto (n=46) or allo (n=18) BMT. A multivariate prognostic model was developed measuring time to relapse, progression or death. Median follow-up was 51.7 months; median EFS for auto and allo BMT was 36 and 3 months, respectively (P=0.001). Significant multivariate predictors of shorter EFS were chemotherapy-resistant disease, KPS <90 and > or =3 chemotherapy regimens pre-BMT. Patients with two to three adverse factors had significantly shorter EFS at 2 years (58 vs 11% in auto; 38 vs 0% in allo BMT patients). Despite a selection bias favoring auto BMT, the model was valid in both auto and allo BMT groups. We were able to differentiate patients at high vs low risk for adverse outcomes post-BMT. This prognostic model may prove useful in predicting patient outcomes and identifying high-risk patients for novel treatment strategies. Validation of this model in a larger cohort of patients is warranted.

Familial and nutritional risk factors for p53 overexpression in colorectal cancer.

Although familial and dietary factors are recognized as important risk determinants for colorectal tumorigenesis, the specific causes of colorectal cancer remain unclear. Studies of p53 genetic alterations have provided clues concerning the etiology of many cancers. This study was designed to determine whether overexpression of the p53 protein is associated with familial and dietary risk factors. Epidemiological data were obtained from 163 colorectal cancer cases and 326 healthy controls. Tumors of all patients were analyzed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Of patient tumors, 44.8% showed p53 nuclear reactivity. Colorectal cases versus controls were three times more likely to report a family history of colorectal cancer [odds ratio (OR), 3.12; 95% confidence interval (CI), 1.77-5.52]. Only cruciferous vegetables exhibited a significant inverse association (OR, 0.59; 95% CI, 0.34-1.02; trend test, P = 0.03) for the highest versus lowest quartiles. Both meat and beef displayed an elevated increase in risk. When cases with p53 overexpression (p53 positive) were compared with cases without p53 overexpression (p53 negative), etiological heterogeneity was suggested for family history of colorectal cancer (OR, 0.39; 95% CI, 0.16-0.93), cruciferous vegetables (trend test, P = 0.12), and beef consumption (trend test, P = 0.08). To estimate the individual relative risks for p53-dependent and p53-independent pathways, each p53 subtype was compared with controls. Cruciferous vegetables exhibited a significant association (OR, 0.37; 95% CI, 0.17-0.82; trend test, P = 0.03) when p53 positive cases were compared with controls. When p53 negative cases were compared with controls, a significant increase in risk was observed for family history of cancer (OR, 4.46; 95% CI, 2.36-8.43) and beef (OR, 3.17; 95% CI, 1.83-11.28; trend test, P = 0.006). The p53 (positive) dependent pathway was characterized by an inverse association with cruciferous vegetables, and p53-independent tumors were characterized by family history and beef consumption. These data may indicate the significance of linking epidemiology and molecular biology in assessing specific etiological pathways.

A meta-analysis of cancer incidence in United States and Canadian native populations.

A meta-analytic approach was used to summarize studies of cancer incidence among Native populations in the United States and Canada. Native males and females were found to have a significantly lower incidence of cancer for all sites combined. Among Native males, kidney cancer was found to exhibit significantly elevated incidence, while significantly lower incidence was found for cancers of the colon, lung, and prostate, and for lymphomas and leukaemias. Native females were found to have significantly elevated incidence for cancers of the gallbladder, cervix, and kidney, while significantly decreased incidence was found for cancers of the colon, breast and uterus, and for lymphomas. The use of meta-analysis to integrate the findings from these studies allowed the identification of subtle differences in cancer incidence. Although these findings are not definitive, they overcome the limited numbers of site-specific cancers reported in many previous studies and are suggestive of general patterns of cancer incidence among Native populations. In addition, these results may be useful in indicating directions for future research involving specific cancer sites with elevated incidence.

A mortality analysis of Native American in New York State, 1980-86.

This investigation examined the mortality experience of Native Americans in New York State, exclusive of New York City, between 1980 and 1986. Compared to the general population of New York State, exclusive of New York City, deaths among Native Americans occurred an average of nine years earlier. Among Native males, elevated risk of death was noted for tuberculosis, diabetes mellitus, pneumonia and cirrhosis. Native females demonstrated an excess of deaths due to diabetes mellitus and cirrhosis. Fewer than expected malignant neoplasm deaths occurred among both Native males and females. A deficit of deaths was observed for colon and lung cancer deaths among Native males and for colon and breast cancer deaths among Native females. While these results are generally in agreement with previous reports, this study did not identify an excess of deaths due to accident-related mortality. Findings from this study, while limited, do serve as crude indicators of the overall health status of Native Americans in New York State and may prove useful in the context of planning and evaluating future health care services among this population.

Historical and contemporary correlates of syphilis and cancer.

BACKGROUND: This study examined the relationship between antecedent syphilis infection and cancer incidence in an attempt to identify specific cancer patterns. METHODS: The study cohort consisted of 16,420 people diagnosed with syphilis between 1972 and 1987 and who were residents of New York State, exclusive of New York City, at time of diagnosis. Incident cancers among cohort members were identified through linkage with files maintained by the New York State Cancer Registry. RESULTS: A total of 350 cancer cases were diagnosed among cohort members. For males and females combined, incidence was significantly elevated for cancers of the oral cavity standardized incidence ratio (SIR = 169, 95% confidence interval [CI]: 109-249), and specifically for cancer of the tongue (SIR = 251, 95% CI: 108-494). Significantly elevated incidence was observed among males for Kaposi's sarcoma (SIR = 2000, 95% CI: 1290-2950). CONCLUSION: While no conclusions may be reached concerning causality, the data do argue for increased cancer surveillance among people with syphilis. Moreover, findings are discussed in light of historical considerations.

Patterns of acute leukaemia occurrence among children in the Chernobyl region.

BACKGROUND: The Chernobyl nuclear accident of 1986 released large quantities of radioactive material causing widespread contamination. In the Ukraine alone, more than 4 million people were exposed to radiation. The exact health consequences of this exposure are still being assessed. METHODS: To ascertain the effect of in utero radiation exposure and the development of leukaemia, a review was undertaken of leukaemia sub-types occurring among children born in the year of the accident (1986) and followed 10 years post-exposure. A comparison was made of leukaemia cumulative incidence rates among children from both an exposed and unexposed oblast. RESULTS: Rate ratios (RR) for the all cell types grouping of leukaemia revealed that rates in the exposed Oblast were significantly elevated for females, males and both genders combined. Rates of acute lymphoblastic leukaemia (ALL) were dramatically elevated for males and to a lesser extent for females. For both genders combined, the RR for ALL was more than three times greater in the exposed compared to the unexposed region. CONCLUSION: Study results suggest that the increased risk of leukaemia and acute leukaemia among those children born in 1986 and resident in radioactively contaminated territories may be associated with exposure to radiation resulting from the Chernobyl accident.

Timing of prenatal care and risk of sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is the leading cause of death during post-neonatal life. Mothers whose infants succumb to SIDS are reported to initiate prenatal care later than control mothers. Previous studies have not always controlled for socioeconomic status (SES) of mothers or other potential confounders such as gestational age or birthweight of infants. The purpose of this study was to assess whether timing of prenatal care adjusted for these potential confounders was an independent risk factor for SIDS. SIDS cases (N = 148) were identified from the Upstate New York livebirth cohort for 1974 (N = 132,948) and compared to randomly selected controls (N = 355) who were frequency-matched on maternal age, race, parity and residence and infant's birth date. Data were abstracted from matched vital certificates (97% response), hospital delivery records (89% response) and selected sample of autopsy reports (100% response). Odds ratios (OR) and 95% confidence intervals (CI) were obtained using unconditional logistic regression. A significant inverse relationship was observed for number of prenatal visits and risk of SIDS; a significant direct relationship was observed between trimester prenatal care initiated and risk of SIDS. The results suggest that timing of prenatal care is important in assessing SIDS risk even after adjusting for potential confounders of early prenatal care utilization.

Immunochemical versus guaiac occult blood stool tests: results of a community-based screening program.

This study was designed to investigate two guaiac-based and one immunochemical faecal occult blood test in a community screening program. A total of 39,000 test kits consisting of Hemoccult II, Hemoccult Sensa and HemeSelect were distributed and of these 8933 (23%) were returned for testing. Follow-up contact with 1165 individuals who tested positive on at least one of the nine test slides was successful in 1076 cases (92.4%). Physician verification in 631 individuals revealed 25 patients (4%) diagnosed with colorectal cancer and 145 (23%) with polyps, of which 120 (82.7%) were adenomatous. The percentage of smaller adenomatous polyps detected relative to the percentage of large polyps (> 1 cm) was: Hemoccult II 31% versus 60%, Hemoccult Sensa 73% versus 80% and HemeSelect 34% versus 57%, respectively. The proportion of adenomatous polyps greater than 2 cm detected by individual tests was even more striking with Hemoccult II positive for 83%, Hemoccult Sensa for 100% and HemeSelect for 75%. Of the 25 patients diagnosed with cancer, 17 (68%) were diagnosed with early-stage disease. A statistically significant trend (P < 0.001) was observed with positive predictive values ranging from 3.3% for individuals with only one positive test to one approaching 40% for individuals with 7 or more positive tests. In this study, the most sensitive predictor of colorectal cancer was found to be the combination of Hemoccult II/HemeSelect. While there was no increase in the positive predicted value for adenomatous polyps < or = 1 cm, there was a direct linear increase for adenomatous polyps > 1 cm.

The impact of age and sex on the incidence of glial tumors in New York state from 1976 to 1995.

OBJECT: In this study the authors describe secular trends in the incidence of three glial tumors--glioblastoma multiforme (GBM), astrocytoma not otherwise specified (ANOS), and anaplastic astrocytoma (AA)--in New York state from 1976 through 1995. They also describe the effect of age and sex on the relative risk (RR) for these tumors, specifically GBM. METHODS: Crude, age-, and sex-specific incidence rates were calculated for each tumor type from 1976 to 1995 by using data from the New York State Cancer Registry. Age-adjusted incidence rates were calculated by the direct standardization procedure, in which the 1970 United States Census Population Standard Million is used. The RR of GBM for the female population was calculated and plotted. Statistical comparisons were made using Pearson's correlation coefficient and regression analysis with the coefficient of variation. CONCLUSIONS: The age-adjusted incidence of these three glial tumors increased during the study period. Increases in age-specific incidence of GBM were primarily limited to patients 60 years of age or older. The reasons for these increases cannot be fully explained with the data. Those in the female population had a lower risk of developing these tumors than those in the male. For GBM, the protective effect of sex was first evident at the approximate age of menarche, was greatest at the approximate age of menopause, and decreased in postmenopausal age strata. The overall protective effect of female sex and the described trend in RR for GBM in the female population suggests that sex hormones and/or genetic differences between males and females may play a role in the pathogenesis of this tumor.

Mortality patterns among the youth of a northeastern American Indian cohort.

Mortality patterns prevalent among American Indian youth have not been well documented. This investigation reports on mortality patterns among the Seneca Nation of Indians from January 1, 1955, through December 31, 1989. The study cohort consisted of 3,033 Seneca tribal members born during the study period. Deaths occurring among cohort members younger than age 25 were identified through a computer match against New York State vital record files. Sex-specific standardized mortality ratios were calculated on the basis of mortality patterns exhibited by the general population of New York State, exclusive of New York City. Males exhibited significantly elevated mortality for all causes combined, for deaths due to all accidents combined, for motor vehicle accidents, and for suicide. Females demonstrated significantly elevated mortality from all accidents combined, for motor vehicle accidents, and for all other types of accidents. Age-specific mortality patterns also varied both by sex and by calendar time. These findings are important to consider in the design of programs aimed at reducing premature mortality among American Indian populations from preventable causes of death.

Years of potential life lost among a Native American population.

The determination of years of potential life lost (YPLL) can aid in monitoring changes in premature mortality among various population groups. While premature mortality has been shown to differ among blacks and whites, patterns of YPLL have not been well established among other racial groups. The Seneca Nation of Indians (SNI) is a Native American group residing primarily in western New York State (NYS). A review of SNI necrology records revealed that 55 percent (510 of 924) of the deaths between 1955 and 1984 occurred before 65 years of age. The proportion of premature deaths among males exceeded the proportion in females. SNI males demonstrated an increased risk of premature death (odds ratio = 1.43) relative to SNI females. Both the percentage of premature deaths and the number of YPLL per death were greater among SNI members compared with NYS residents. Almost one-half of all YPLL among the SNI were attributable to accidents and injuries. Heart disease, digestive diseases, and malignant neoplasms also represented important contributors to YPLL for both SNI males and females. This investigation identifies important causes of premature death among a Native American population and underscores the preventable nature of premature loss of life.

Comparison of Native American births in upstate New York with other race births, 1980-86.

The purpose of this study was to describe the neonatal characteristics of Native American (Indian) infants and the antenatal characteristics of their mothers as compared with white, black, and other race infants. The study population comprised 979,444 live births to upstate New York (exclusive of New York City) resident mothers between 1980 and 1986. Data were abstracted from vital records (birth certificates) and analyzed using a variety of descriptive statistics. Mothers of Native American and black infants had similar antenatal profiles (that is, younger, higher parity, lower educational attainment, and delayed initiation of prenatal care), which differed from mothers of white or other race infants. Despite having at-risk mothers, Native American infants were similar to white and other race infants with respect to the percentage of births that were considered low birth weight or premature. Black infants were twice as likely as the other three groups of infants to be low birth weight or premature. These findings suggest that other factors appear to be important in determining neonatal outcome and that typical at-risk antenatal profile of mothers may not be consistent across all racial groups.

Racial variation in spontaneous fetal deaths at 20 weeks or older in upstate New York, 1980-86.

The distribution of spontaneous fetal deaths (at age 20 weeks or more) by maternal race has received considerably less study than other adverse pregnancy outcomes. The purpose of this study was twofold--(a) to describe spontaneous fetal deaths among white, black, and American Indian women and (b) to determine if there was any variation by International Classification of Diseases, Ninth Revision (ICD-9) cause of death, gestational age at death, or maternal age at loss among these groups of mothers. Using the fetal death certificate registry maintained by the New York State Department of Health, 8,592 spontaneous fetal deaths at age 20 weeks or more were identified among upstate (exclusive of New York City) mothers between 1980 and 1986. By race it was 7,300 for white women, 1,257 for black women, and 27 for American Indian women. Spontaneous fetal death rates varied by maternal race as listed on vital records--black, 13.5 per 1,000 total births, white, 8.3, and American Indian, 8.1. The three leading causes of death (ICD-9,779, 762, and 761) did not vary by maternal race. Gestational age at death, imputed from last menstrual period, did vary by maternal race. Fetal deaths to white and black mothers were observed to occur most often between 24 weeks of pregnancy (39 percent) and 32 weeks (43 percent), while American Indian fetal deaths generally occurred later (more than 33 weeks) in pregnancy (41 percent). Most spontaneous fetal deaths occurred to mothers ages 20-29 regardless of race. Black teenage mothers, however, experienced the largest proportion of losses(23 percent) compared with white (10 percent) and American Indian (I I percent) teenage mothers.

Health status of American Indians/Alaska Natives: general patterns of mortality.

BACKGROUND AND OBJECTIVES: Investigations of American Indian and Alaska Native (AI/AN) populations suggest patterns of mortality that differ from the general population. Mortality data reveal excess overall mortality among AI/ANs, as well as excesses for specific causes of death, including accidents, diabetes, liver disease, pneumonia/influenza, suicide, homicide, and tuberculosis. A relative deficit of deaths has been noted for heart disease, cancer, and HIV infections. It is important that physicians demonstrate cultural competence so they may provide quality medical care for the populations they serve. Activities such as provider education, risk assessment, and emphasis on preventive services are offered to facilitate integration into teaching curricula. Knowledge of distinctive mortality patterns among AI/ANs will help clinicians recognize the unique needs of these patients.

Hypothyroidism and diabetes mellitus in an American Indian population.

BACKGROUND: The clinical relationship between diabetes and hypothyroidism is becoming more widely recognized. Although American Indians are disproportionately afflicted with diabetes, the occurrence of hypothyroidism within this group has not been previously reported. METHODS: We present data from a retrospective chart review of health clinic data from a rural isolated northeastern tribe. A total of 156 cases of diabetes and 25 cases of hypothyroidism were identified among 892 eligible individuals living in the service area. RESULTS: Both conditions exhibited strong sex differences. The prevalences of diabetes (21%) and hypothyroidism (5%) among women were higher than those observed among men (13% and 0.2%, respectively). The overall prevalence of hypothyroidism among women with diabetes (8.8%) varied by age ranging from 5% among women younger than 60 years to 21% among women aged 60 years and older. CONCLUSIONS: Our findings support the need for further investigation of the association between diabetes and hypothyroidism in American Indian populations with high prevalence rates of diabetes. This association may be of particular interest to family physicians and other clinicians caring for American Indian populations.

A bibliometric analysis of cancer among American Indians & Alaska Natives, 1966-1993.

A bibliometric analysis was employed to objectively assess scientific studies published between 1966 and 1993 which have described cancer among American Indians and Alaska Natives. Searches of the MEDLINE (1966-1993) and CANCERLIT data bases (1983-1994) were used to identify relevant publications. In addition to examining publication sources and quantitative temporal trends, further bibliometric analyses were completed by considering a subset of papers published between 1982 and 1992. A total of 128 studies of cancer among American Indians and Alaska Natives were published between 1966 and 1993; 62 of these articles (48%) appeared between 1988 and 1993. Nine journals accounted for 53% of the total publications. The subset of 68 papers published between 1982 and 1992 were cited a total of 388 times in 136 different journals; the median number of citations was 2. Results demonstrate a limited number of published papers on cancer among American Indians and Alaska Natives. It is hoped that this paper will increase the awareness of cancer as an important health problem among American Indian and Alaska Natives and thereby serve to stimulate additional cancer-related research activities involving these groups.

Tribal-based cancer control activities among Alaska Natives: services and perceptions.

Cancer has become a significant health problem in American Indian and Alaskan Native (AI/AN) communities. Despite the precipitous rise in cancer rates, limited data are available concerning cancer control services operative in these communities. To address this issue, a cross-sectional survey of all federally recognized tribes was undertaken to ascertain the breadth of cancer control activities offered and Tribal Health Directors perceptions of and priorities ascribed to cancer. This article presents responses given by AN Health Directors juxtaposed to those proffered by AI Health Directors. Nearly three-quarters (71%) of respondents perceived cancer rates to be increasing. Cancer was found to rank third, fifth among AI Health Directors, among seven health conditions when Directors were asked to rank their Tribe's commitment to confronting each one. Awareness of cancer as a public health concern coupled with competing health problems relegates cancer control activities to a lower priority. Findings underscore the need to elevate the issue of cancer in Indian Country as well as to educate investigators to become more sensitive and responsive to other Tribal health issues.