Assuring access to state-of-the-art care for U.S. minority populations: the first 2 years of the Minority-Based Community Clinical Oncology Program.

BACKGROUND: The Minority-Based Community Clinical Oncology Program (MBCCOP) was initiated in September 1990 to expand the National Cancer Institute's (NCI's) clinical trials network to minority populations. Institutions, organizations, and/or physician groups that had more than 50% of new cancer patients from minority groups were eligible to participate. There has been no previous evaluation of the MBCCOP. PURPOSE: This study was designed to describe the early implementation of the MBCCOP and identify the challenges that have emerged in developing a network aimed at increasing the participation of minority populations in clinical trials. METHODS: Data were taken from primary and secondary sources, including site visits and patient log data, that described performance of 12 MBCCOP centers initially funded in September 1990. Accrual was measured by the number of credits earned per MBCCOP for patients enrolled in research protocols for cancer treatment or for prevention and control, which includes activities such as early detection, pain control, and rehabilitation. These accrual credits, assigned by the NCI, were based on the complexity of the protocol and the amount of resources expected to be required for accrual of patients by the MBCCOP. RESULTS: Data for the first 2 years of the MBCCOP showed that 344 patients were accrued to trials of treatment protocols from June 1, 1990, to May 31, 1991, and this number increased to 470 during the second accrual year, June 1, 1991, to May 31, 1992. Similarly, accrual of patients to cancer prevention and control studies increased from 256 in 1990-1991 to 423 in 1991-1992. More than 70% of the MBCCOP patients entered in studies were from minority populations. The proportion of eligible MBCCOP patients entered into treatment protocols was identical with that experienced by the initial Community Clinical Oncology Program (CCOP). Results also demonstrated that MBCCOP centers operate in an environment characterized by socio-economic decline and limited resources, both having substantial effects on the implementation of clinical trials among minorities. While minority patients are willing to participate in clinical trials, there are profound barriers involving language, logistics, and the appropriateness of available protocols. Participating physicians, nurses, and support personnel report a high level of agreement with program goals and have developed unique approaches to meeting the challenges faced in the implementation of this program. CONCLUSIONS: The MBCCOPs have demonstrated their ability to participate in clinical trials. Evaluation reveals, however, that they are emerging organizations influenced by factors endemic to the community they serve and their own structure. The MBCCOPs are confronting substantial challenges, yet they provide an important link to the overall NCI clinical trials network.

Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials.

BACKGROUND: The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. PURPOSE: Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. METHODS: During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups: birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. RESULTS: Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. CONCLUSIONS: Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. IMPLICATIONS: This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.

Geographic, age, and racial variation in the treatment of local/regional carcinoma of the prostate.

PURPOSE: Prostate cancer is one of the most common cancers in men. Incidence rates increase with age and are substantially higher in black men than white men. This study examines the variations in the use of radical prostatectomy and radiation by geographic area, age, and race. MATERIALS AND METHODS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End-Results Program (SEER) were used to examine treatment differences. Current treatments generally consist of prostatectomy, radiation, or careful observation for clinically localized or regional disease. RESULTS: The age-adjusted proportion of men, age 50 and older, who received radical prostatectomy increased sharply between 1984 and 1991, from 11.0% to 32.3% among men with local/regional disease. The choice of treatment varied widely by geographic regions. In 1991, the proportion that received prostatectomy was highest in Utah (47.8%) and lowest in Connecticut (22.5%) among men with localized and regional disease. The increase in radical prostatectomy was not limited to younger men. Although the rates increased for blacks, black men had lower age-adjusted rates of prostatectomy than whites in all years of the study. CONCLUSION: The SEER data show a clear trend toward more aggressive treatment, especially prostatectomy. However, the proportion of black men who received prostatectomy was substantially lower than that of white men and this disparity does not appear to be changing.

Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database.

PURPOSE: Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS: Breast cancer records were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-). RESULTS: Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-. CONCLUSION: Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.

After a treatment breakthrough: a comparison of trial and population-based data for advanced testicular cancer.

PURPOSE: To determine to what extent the benefits of cisplatin-based combination chemotherapy have been disseminated to all American men diagnosed with advanced testicular cancer. PATIENTS AND METHODS: One hundred seventy-two advanced testicular cancer cases from five population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program diagnosed from 1978 to 1984 were compared with 133 diagnostically comparable cases from the Memorial Sloan-Kettering Cancer Center (MSKCC) vinblastine, dactinomycin, and bleomycin (VAB) regimens 7 through 9. Exclusions were made in both series for cases with elevated markers only, abdominal disease only, or extragonadal tumors. Ratings of extent of disease using the Indiana University system (minimal/moderate or advanced) were available for the MSKCC cases, and were determined retrospectively on the SEER cases based on information abstracted from medical records. RESULTS: Among the SEER cases, 89% reported receiving chemotherapy, and 95% of these received cisplatin-containing regimens. Survival among the MSKCC patients was significantly better than for the SEER cases in the minimal/moderate extent of disease category (95% and 73% 3-year survival rate, respectively); however, the difference for advanced cases was only marginally significant (52% and 40% 3-year survival rates, respectively). Survival did not vary significantly by year of diagnosis in either series. CONCLUSION: Although most of the patients in the SEER series received cisplatin-based chemotherapy, this alone did not produce results equivalent to that in the MSKCC series. Since the patients were selected to be as diagnostically comparable as possible at baseline, remaining differences in survival may be due to adherence to a fixed regimen and level of dose-intensity, adequacy of diagnostic work-up, implementation of salvage therapies and debulking surgery, and unknown factors related to who is willing and able to travel to a tertiary care center for treatment. Whatever the reason for not achieving optimal results in the SEER series, the very modest survival improvements over the time period 1978 to 1984 indicates that the differences in outcome between the two series were basically stable over the study period.

A Phase II study of high-dose tamoxifen in patients with hormone-refractory prostate cancer.

Micromolar concentrations of tamoxifen inhibit the activity of protein kinase C and were recently shown to inhibit prostate cancer cell growth in preclinical studies. Because micromolar concentrations can be attained with high-dose therapy, the clinical activity of high-dose tamoxifen was evaluated in patients with metastatic adenocarcinoma of the prostate. Between December 1993 and February 1997, 30 patients with hormone-refractory metastatic adenocarcinoma of the prostate were continuously administered tamoxifen at 160 mg/m2/day. Therapy was continued until disease progression. All study patients had failed prior treatment with combined androgen blockade, had castrate levels of testosterone, and were heavily pretreated, having received a median of three prior regimens. The average steady-state plasma concentration of tamoxifen was 2.96+/-1.32 microM (mean +/- SD). Grade 3 neurotoxicity was observed in 29% of patients and was rapidly reversible and readily managed with dose modification. Otherwise, grade 3 toxicities were rare. One partial response (80% decline in prostate-specific antigen) was observed (3.3%), whereas disease stabilization was observed in six patients (20%), for a combined partial response/stable disease response rate of 23%. Median time to progression was 2.1 months, and median survival time was 10.5 months. High-dose tamoxifen therapy was well tolerated and associated with micromolar concentrations of tamoxifen in human plasma, and it demonstrated activity, albeit limited, in a heavily pretreated patient cohort with hormone-refractory prostate cancer. These findings suggest that further investigation of the role of protein kinase C modulation in prostate cancer is warranted.

Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal.

Management of prostate cancer progression after failure of initial hormonal therapy is controversial. Recently, the activity of the simple discontinuation of antiandrogen therapy has been established by several groups, as well as the enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide and hydrocortisone). Furthermore, suramin has generated considerable interest following reports of response rates ranging from 17 to 70%. More recently, suramin response rates of 18 and 22% have been reported when the potential confounding variables of flutamide withdrawal and hydrocortisone were prospectively controlled. On the basis of the activity of combining aminoglutethimide with flutamide withdrawal, we designed a protocol in which suramin was combined with aminoglutethimide in two cohorts of patients (those with simultaneous antiandrogen withdrawal compared to those who had previously discontinued antiandrogen therapy). Eighty-one evaluable patients were enrolled in this study between June 1992 and November 1994. Patients were a priori divided into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the patients were enrolled into the trial. For the group that discontinued antiandrogen prior to enrolling in therapy, the partial response rate (> 50% decline in PSA for > 4 weeks) was 14.2%, whereas the partial response was 44% for those patients who discontinued their antiandrogen at the time of starting suramin and aminoglutethimide. The median time to progression was 3.9 months in patients failing prior antiandrogen withdrawal and 5.5 months in those patients having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference). The progression-free survival estimate at 1 year for patients having prior antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%]. For those patients who experienced antiandrogen withdrawal simultaneous with the treatment, the progression-free survival estimates at 1 and 2 years were 27.1 (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%). The median survival time for those patients having prior antiandrogen withdrawal was 14.2 months, whereas the median survival was 21.9 months for those having concomitant antiandrogen withdrawal (P = 0.029 for the overall difference). In conclusion, the partial response rate of 44% for those who had concomitant flutamide withdrawal with adrenal suppression was consistent with that of other reports using a similar maneuver. Although this study was not randomized and thus we should not over-interpret the results, flutamide withdrawal plus adrenal suppression appears to have greater activity than flutamide withdrawal alone. Furthermore, these data suggest that suramin adds little to the response rate observed for other adrenal suppressive agents in the presence of antiandrogen withdrawal. This interpretation is in agreement with those studies controlling for adrenal suppression and flutamide withdrawal prior to suramin administration, which noted modest activity of short duration. Given that antiandrogen withdrawal is now accepted as an active maneuver for a subset of patients progressing after maximum androgen blockade, we propose that future trials attempting to maximize response rates incorporate this maneuver whenever possible into prospectively designed regimens.

5-Alpha-reductase inhibition and prostate cancer prevention.

Studies of prostate biology support the concept that dihydrotestosterone is the principal androgen responsible for normal and hyperplastic growth of the prostate gland. Cancer is a process of malignant transformation evolving over time, involving cellular growth and division. Therefore, an altered endocrine state, such as suppression of dihydrotestosterone activity, may have an impact on prostate cells inhibiting carcinogenic transformation. In vitro and in vivo preclinical observations support this hypothesis. A placebo-controlled randomized trial using finasteride, an inhibitor of the enzyme that converts testosterone to dihydrotestosterone, is planned. The endpoint of this trial will be reduction of prostate cancer incidence.

Prostate cancer prevention trials in the USA.

There is dramatic international variation in prostate cancer mortality rates. The variation suggests that the disease has an environmental cause and encourages the search for a way to prevent it. Androgenic stimulation over a period of time, perhaps due to a high fat diet, has been suggested as a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. 5-Alpha-reductase inhibition through drugs like finasteride have been shown to decrease androgenic stimulation of the prostate. A clinical trial is underway using finasteride to assess this hypothesis. Epidemiological and laboratory studies also suggest that those with high selenium and vitamin E intake have a lower risk of prostate cancer. Recent serendipitous findings of two randomised clinical trials support this. A study to assess these compounds is currently being designed. Other promising but less developed interventions in the chemoprevention of prostate cancer include vitamin D supplementation and diet modification.

The study of untreated syphilis in the negro male.

PURPOSE: The participation of minorities in clinical studies is the subject of much discussion and has even become the subject of Federal law. The project known as the Tuskegee Syphilis Study and officially titled "The Tuskegee Study of Untreated Syphilis in the Negro Male," is one of the great debacles of American medicine and a national shame. Despite the fact that its existence is well known, many do not know the historical facts of the study nor the context of the study. My purpose here is to recount the facts of the study and its historical context. METHODS: The history recounted here is taken from documents gathered during a U.S. Senate investigation of the study, original papers located in National Library of Medicine, and books about the trial. RESULTS: The trial began in 1931 as a survey of the natural history of untreated tertiary syphilis in Black men. This study enrolled 399 men with syphilis and 201 uninfected men to serve as controls. All were at least 25 years old at enrollment. The men were told they were in a study, but never educated about the implications. Later, men were not informed that there was a treatment for effective treatment for their disease--a treatment that was being withheld from them. This trial continued till 1972. CONCLUSION: Many of the issues that led to the study and caused it to continue for 40 years still exist. The lessons of the Public Health Study of Untreated Syphilis in the Untreated Negro include the dangers of paternalism, arrogance, blind loyalty, and misuse of science. "Those who do not appreciate history are condemned to repeat it" (Alfred North Whitehead).

The future of prostate cancer prevention.

The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention.

Chemoprevention of prostate cancer.

Primary prevention of prostate cancer is a relatively new concept. Through large-scale studies it is possible that we may be able to define better the risk for prostate cancer and identify those who would benefit from an intervention to lower their risk of disease. As risk for prostate cancer is better defined, a number of interventions may eventually be tested. Several interventions are sufficiently mature that they can be implemented in large-scale trials. Diet modification is an intervention that is ready for evaluation. It may also have additional benefits by decreasing mortality from other malignancies and cardiac disease. 5 alpha-reductase inhibitors are also ready for testing. The National Cancer Institute and its clinical cooperative groups have begun a large trial to assess finasteride in the prevention of prostate cancer.

Cancer screening.

Especially in the emotionally charged field of cancer screening, which can have substantial public health implications for large numbers of healthy, asymptomatic people, it is important to achieve strong levels of evidence before promulgating new screening tools. This review of screening study methodology is intended to help the reader weigh such evidence and to evaluate reports which appear in the literature. It is an attempt to go beyond the often-stated intuition that early cancer detection finds cancers when they are easier to treat, at a time when survival is best. Examples tell us that sometimes this assumption has been true, sometimes not. A familiarity with the hidden biases in the supposition can be translated into everyday medical practice for screening tests in general. The practitioner can then match the strength of recommendation with the strength of the evidence behind the recommendation.

Cancer chemoprevention trials.

Clinical Trials Referral Resource is designed to serve as a ready reference for oncologists to help identify clinical trials that might be suitable for their patients. We hope it also will enhance accrual to clinical trials by informing practicing oncologists of ongoing protocols. Currently in the United States less than 10% of eligible adult patients are entered on clinical trials. The result is a delay in answering important therapeutic and scientific questions and disseminating therapeutic advances to the general oncology community. It should be emphasized that including a specific trial does not imply that it is more important than another trial. Among the criteria for selection are that the trial is addressing an important question and is not expected to close in the immediate future (less than 1 year), and that initial staging or laboratory tests required for patient eligibility are widely practiced and available. Information on other protocols can be accessed via Physician's Data Query (PDQ). We emphasize that this is an attempt to encourage referral of patients to these trials. We are specifically not soliciting additional members for the cooperative groups, nor are we suggesting how practicing oncologists should be treating patients not in a study. This month's installment of Clinical Trials Referral Resource is devoted to cancer chemoprevention trials. For patient entry information contact the person listed in each individual trial.

Analysis of autopsy evaluations of ovarian cancer patients treated at the National Cancer Institute, 1972-1988.

Between 1972 and 1988, more than 500 women were treated for ovarian cancer at the National Cancer Institute in Bethesda, Maryland on approved experimental treatment protocols. Of these, 73 underwent autopsy evaluation on the National Cancer Institute campus. We have analyzed the autopsy reports of those individuals to determine the patterns of disease spread at death. By comparison with the literature, the demographics of the cohort did not differ from previously published reports, other than the extent of chemotherapy received antemortem. Median survival of the cohort was 15.6 months (range, 1.7-108.3 months), and median age at diagnosis was 55 years (range, 24-74 years). The median number of treatments regimens received was two (range, 1-6). The pattern of disease spread at autopsy was different from that in previously published work in that there was a higher proportion of patients with disease found in liver parenchyma, lung pleura, and the pericardium. Patients who received cisplatin as part of their initial treatment regimen had a higher incidence of metastases to the adrenal glands, thoracic nodes, bladder, and liver parenchyma, which was not explained by differences in survival. Median survival for patients who received cisplatin as part of their initial therapy was 15.6 months, compared with a median of 15.4 months for patients who did not. These data suggest a changing pattern of disease spread in patients with ovarian cancer receiving aggressive chemotherapy. This may be caused by some effect of platinum-based therapy on the metastatic potential of the tumor.

National cancer clinical trials: children have equal access; adolescents do not.

PURPOSE: To determine whether adolescents with cancer, who in comparison to younger patients have a higher cancer incidence and lower mortality reduction, have equal access to national cancer clinical trials. METHODS: The ethnic/racial distribution of 29,859 subjects < 20 years of age entered onto National Cancer Institute-sponsored clinical trials between January 1, 1991, and June 30, 1994, was compared with the expected distribution of patients of the same age in the United States. RESULTS: The Children's Cancer Group and Pediatric Oncology Group had 29,134 (97.6%) of the total study entries among < 20-year-old subjects during the 3.5 years of surveillance. The adult cooperative groups accounted for < 3% of the clinical trials entries in the 15-19-year age range. When analyzed nationally by region, the under-representation of the older adolescent subjects was universal. From other analyses, the two pediatric cooperative groups were estimated to have registered > 94% of the children < 15 years of age who were expected to have been diagnosed to have cancer, but only 21% of the cancer patients in the 15-19-year age group. CONCLUSIONS: The national pediatric cancer cooperative groups allow the majority of American children < 15 years of age and their families equal opportunity to access clinical cancer trials, regardless of race or ethnicity. Among patients 15-19 years of age, however, > 75% are not being enrolled by any cooperative group sponsored by the National Cancer Institute. Thus, older adolescents are disadvantaged with respect to access to the national clinical trials, regardless of their race or ethnicity.

Measures of renal function in patients with cisplatin-related chronic renal disease.

Twenty-seven patients with advanced stage refractory ovarian cancer were studied to determine if chronic stable cisplatin-related renal dysfunction was present. Medical histories were examined to determine the types of therapy previously received as well as the total previous platinum doses received that ranged from 200 to 2,100 mg/m2. Standard assessments of renal function were made prior to administering current chemotherapy or immunotherapy to the patient, which included 24-hour creatinine clearance, serum creatinine, and blood urea nitrogen (BUN). For patients with a 24-hour creatinine clearance of less than 60 mL/minute, serum creatinine was highly variable (range: 0.9 to 2.0 mg/dL) and was not related to the degree of diminution in the 24-hour creatinine clearance value. Conversely, for patients with a serum creatinine of less than 1.5, the 24-hour creatinine clearance values varied by almost three-fold, ranging between 46 and 120 mL/minute. Two patients with serum creatinines of less than 1 had creatinine clearances of less than 50 mL per minute. Similarly, BUN measurements did not correlate with 24-hour creatinine clearance values, and the 24-hour creatinine clearance value was not related to the total cumulative platinum dose. We conclude that patients who receive substantive doses of cisplatin may experience chronic stable cisplatin-related renal dysfunction and that serum creatinine cannot be relied on to assess the degree of renal compromise. In such patients, we recommended that the 24-hour creatinine clearance value should be used when medical management is influenced by renal function.

The epidemiology of prostate cancer in the United States.

OBJECTIVES: To provide a review of prostate cancer epidemiology. DATA SOURCES: Journal articles and the Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Numerous risk factors for prostate cancer have been identified. Incidence and mortality rates are higher in certain countries and among racial ethnic groups. Environmental and dietary influences are likely to be significant causes of prostate cancer. Distinguishing those cancers that are clinically significant from those that are not remains a central concern in prostate cancer research. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of epidemiologic patterns and trends will assist nurses in recognising persons at high risk for the development of prostate cancer and should result in tailored educational interventions.

Association of Helicobacter pylori infection with gastric cancer.

BACKGROUND: Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. METHODS: We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. RESULTS: H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. CONCLUSIONS: New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.