The influence of comorbid conditions on racial disparities in endometrial cancer survival.

OBJECTIVE: There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race. STUDY DESIGN: Two hundred seventy-one black women and 356 white women who had been diagnosed with endometrial cancer from 1990-2005 were identified from a large urban integrated health center. A retrospective chart review was conducted to gather information on comorbid conditions and other known demographic and clinical predictors of survival. RESULTS: Black women experienced a higher hazard of death from any cause (hazard ratio [HR] 1.51; 95% confidence interval [CI], 1.22-1.87) and from endometrial cancer (HR, 2.42; 95% CI, 1.63-3.60). After adjustment for known clinical prognostic factors and comorbid conditions, the hazard of death for black women was elevated but no longer statistically significant for overall survival (HR, 1.22; 95% CI, 0.94-1.57), and the hazard of death from endometrial cancer remained significantly increased (HR, 2.27; 95% CI, 1.39-3.68). Both black and white women with a history of hypertension experienced a lower hazard of death from endometrial cancer (HR, 0.47; 95% CI, 0.23-0.98; and HR, 0.35; 95% CI, 0.19-0.67, respectively). CONCLUSION: The higher prevalence of comorbid conditions among black women does not explain fully the racial disparities that are seen in endometrial cancer survival. The association between hypertension and a lower hazard of death from endometrial cancer is intriguing, and further investigation into the underlying mechanism is needed.

Racial differences in oncogene mutations detected in early-stage low-grade endometrial cancers.

OBJECTIVE: To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. METHODS: Patients with endometrial cancer from a large urban hospital were identified through medical records, and representative formalin-fixed paraffin-embedded tumor blocks were retrieved. The study sample included 150 patients (84 African Americans) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay version 1.0 (Sequenom) were used to test for 238 mutations in 19 common oncogenes. The χ(2) test and the Fisher exact test were used to assess differences in distribution of variables by race and oncogene mutation status. RESULTS: There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). Most of the mutations were found in PIK3CA (16/20). Thirteen percent of endometrioid tumors harbored mutations (11 PIK3CA and 2 KRAS) as did 29% of the malignant mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low-grade endometrioid cancers, tumors from African American patients were significantly associated with harboring either a KRAS or PIK3CA mutation (P = 0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in African American women. CONCLUSIONS: This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.

High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients.

OBJECTIVE: Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. MATERIALS AND METHODS: 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. RESULTS: Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). CONCLUSION: Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

Disparities in gastric cancer outcomes among Asian ethnicities in the USA.

BACKGROUND: Survival for gastric cancer is reportedly higher in Asians than for other races. It is unclear whether differences in outcome exist among Asian ethnicities. Our objective was to assess gastric cancer survival in Asian ethnic groups in a large heterogeneous population. METHODS: Asian-Americans treated for gastric adenocarcinoma between 1988 and 2006 were identified from the Los Angeles County Cancer Surveillance Program. Patients were stratified and compared by ethnicity (Korean, Japanese, Chinese, Vietnamese or Filipino). RESULTS: Of the 1,817 Asian-Americans in the study cohort, 45% (n = 810) were Korean, 25% (n = 462) were Chinese, 11% (n = 193) were Japanese, 10% (n = 188) were Filipino, and 9% (n = 164) were Vietnamese. For the entire cohort Koreans and Filipinos had the longest and shortest median survival (MS), respectively (22.4 and 10.3 months, respectively; P < 0.001). Multivariate analysis demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.08-1.73, P = 0.008; and HR 1.71, 95% CI 1.37-2.13, P < 0.001, respectively]. In the surgical cohort, Koreans and Filipinos had the longest and shortest survival, respectively (MS of 57.8 and 21.7 months, respectively; P < 0.001). Multivariate analysis of the surgical cohort also demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity (HR 1.61, 95% CI 1.22-2.13, P < 0.001; and HR 1.66, 95% CI 1.24-2.22, P < 0.001, respectively). CONCLUSION: There are differences in gastric cancer survival among Asian ethnicities. Future studies addressing varying environmental exposures and molecular expression patterns in gastric cancer are warranted to better understand these disparities in outcome.

Epithelial ovarian cancer mortality among Hispanic women: Sub-ethnic disparities and survival trend across time: An analysis of SEER 1992-2013.

BACKGROUND: Over the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking. OBJECTIVES: To examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992-2013. METHODS: The disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models. RESULTS: The 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the "Other" Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P < 0.001). The OC-specific death hazards in Mexicans (HRadj: 0.82, 95%CI: 0.67-1.00, P = 0.048), South or Central Americans (HRadj: 0.77, 95%CI: 0.62-0.96, P = 0.005) and Other Hispanics (HRadj: 0.76, 95%CI: 0.63-0.92, P = 0.038) were significantly lower than for Puerto Ricans. Mortality rates of Cubans and Puerto Ricans were not significantly different. During 1992-2008, there were non-significant increasing trends in the 5-year all-cause and OC-specific survival rates: from 43.37% to 48.94% (APC = 0.41, P = 0.40) and from 48.72% to 53.46% (APC = 0.29, P = 0.50), respectively. CONCLUSIONS: OC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research.

Prognosis of subtypes of the mucinous breast carcinoma in Chinese women: a population-based study of 32-year experience (1983-2014).

PURPOSE: The heterogeneous nature of the mucinous breast cancer (MBC), with its pure (PMBC) and mixed subtypes (MMBC), calls for precise prognosis assessment. METHODS: We analyzed 197 consecutive MBC patients, including 117 PMBC and 80 MMBC, who were treated from 1983 to 2014. The clinicopathological features, treatment choice, disease-free survival (DFS) and overall survival (OS) were compared among PMBC, MMBC and MMBC subgroups. Prognostic factors of PMBC and MMBC were identified. RESULTS: Compared to PMBC, MMBC had more lymph node metastasis (p = 0.043), Her2 positivity (p = 0.036), high Ki-67 index (defined as>20%, p = 0.026) and anti-Her2 targeted therapy (p = 0.016). The 5-year DFS of PMBC and MMBC were 90.4% and 86.2%, whereas the 5-year OS were 99.0% and 98.7%. No significant difference was found in DFS or OS among all MBC subtypes. High Ki-67 (p = 0.020) appeared as DFS factor in PMBC, while anti-Her2 targeted therapy (p = 0.047) as the DFS predictors in MMBC. CONCLUSION: MMBC manifested similar 5-year survival to PMBC in Chinese woman, suggesting that intra-tumoral heterogeneity might not interfere with MBC short-term prognosis.

Epstein-Barr virus-associated gastric carcinoma in Kazakhstan.

AIM: To investigate the incidence of Epstein-Barr virus-associated gastric cancer (EBV-GC) in Kazakhstan and to compare it with that in Russia, Western and Asian countries in order to evaluate the significance of epidemiopathologic and ethnic factors. METHODS: In situ hybridization (ISH) of EBV-encoded small RNA-1 (EBER-1) was used to identify the presence of EBER-1 signal in 139 formalin-fixed and paraffin-embedded GC tissues from Kazakhstan. RESULTS: EBER-1 expression was observed in the nuclei of 10% of the cases of GC (14/139), but not in the surrounding normal mucosa. The incidence of the diffuse type of EBV-GC was significantly higher in Kazakhstan (14%, 13/91) than that of the intestinal type (2%, 1/48). Furthermore, the incidence was significantly higher in males (14%, 12/89) than in females (3.7%, 2/53) from all countries. The overall incidence of EBV-GC increased from 6.7% in Asian countries to 8.7% in Russia, 10.1% in Kazakhstan and 16% in Western countries. CONCLUSION: Geographical differences in the incidence of EBV-GC may reflect the epidemiologic factors and/or dietary habits independent of histological type and sex.

Surgical pathology of colorectal cancer in Filipinos: implications for clinical practice.

BACKGROUND: A number of studies published in the Philippine literature have demonstrated certain peculiar clinicopathologic characteristics of colorectal cancer among Filipinos. This study presents the latest data and analyzes their implications for clinical practice. STUDY DESIGN: The pathology reports of all patients who underwent operation for colorectal cancer at the Philippine General Hospital over a period of 7 years were reviewed. RESULTS: One thousand two hundred seventy-seven patients were included. The male to female ratio was almost 1:1. The majority of patients were in the sixth and seventh decades of life, with a mean age of 55.3 years. Patients 40 years of age and younger made up 17% of the total. The site of cancer in order of frequency was rectum (49.8%), left colon (27.9%), and right colon (21.4%). Cancers of the right colon were more common in women, and rectal cancers were more frequent in men. Seventy-six percent of the tumors were well to moderately differentiated adenocarcinomas, and 6.7% were poorly differentiated. Mucinous and signet ring carcinomas were found in 11% and 1% of cases, respectively. Forty-four percent of patients had localized disease at the time of operation, 54% had regional disease, and 2% had disseminated disease. Associated predisposing conditions noted were polyps (4.7%), schistosomiasis (3%), and tuberculosis (1.5%). CONCLUSIONS: Colorectal cancer in Filipinos exhibits a number of unique clinicopathologic features, such as a higher proportion of early age of onset tumors, more advanced stage at presentation, an association with chronic granulomatous diseases, and relatively rare occurrence with polyps. This might suggest the possibility of a different pathway for tumor development of colorectal cancer in this population of patients. Also, current screening guidelines advocated for the Western population might not be appropriate for Filipinos.

Colorectal cancer in young black patients.

A higher percentage of young black patients are discovered with a more advanced stage of colorectal cancer than is reported for white patients. To evalute this phenomenon, various prognostic factors in young colorectal cancer patients at Howard University Hospital were studied.

[Ovarian cancer in Israel, 1960-1989].

In Israel ovarian cancer ranks among the most common malignant diseases in women. It is also one of the main causes of death from cancer in females in this country. Our population is composed of immigrants from diverse social, cultural, and geographical backgrounds, and only a sector of the inhabitants, mainly the younger generation, is Israeli-born. This study evaluates the trends of epidemiological and clinical data on ovarian cancer during 3 decades, 1960-1989, and includes a total of 5,786 cases of ovarian cancer. Information was obtained from the Central Israel Cancer Registry of the Ministry of Health and from the Central Bureau of Statistics. The incidence was stable during the survey period and was about 15-17/100,000 in women over the age of 15. Most (90%) were diagnosed over the age of 40. In women of European/American origin the incidence of ovarian cancer is 3 times greater than in women of Asian/African origin. The rate in the Israeli-born is between those of the other 2 groups, but closer to that of the European/American group. Over 70% were diagnosed with advanced disease (stage III-IV). Prognosis improved during the period of the study: 5-year survival was 19% in the early 60's and 31% in the 80's. During the last decade of the survey improvement was mainly in 2-year survival (from 38.5% to 60%).

Primary cutaneous mucinous carcinoma: a systematic review and meta-analysis of outcomes after surgery.

IMPORTANCE: Evidence-based treatment guidelines are not available for primary cutaneous mucinous carcinoma (PCMC). OBJECTIVE: To assess outcomes associated with surgical treatment of PCMC. DATA SOURCES: MEDLINE, Cumulative Index to Nursing and Allied Health, and Embase from 1952 to 2010. Search terms were "primary cutaneous mucinous carcinoma," "primary mucinous adenocarcinoma of the skin," "primary mucinous sweat-gland carcinoma," and "endocrine mucin-producing sweat gland carcinoma." STUDY SELECTION: Articles describing primary data on treatment (ie, case reports, case series, and cohort studies) of any patients with PCMC. A total of 116 articles were identified, with 90 of these assessed for eligibility and 87 used for final analysis. DATA EXTRACTION AND SYNTHESIS: Each case was verified to be of primary cutaneous origin by 2 observers. Histopathologic descriptions were confirmed to be consistent with PCMC. Extracted fields included age, sex, race, lesion duration, tumor diameter, method of treatment, follow-up, and whether the lesion recurred or metastasized. MAIN OUTCOMES AND MEASURES: Outcomes were dichotomized into good and bad depending on the presence of recurrence or metastasis during follow-up. Multivariate logistic regression analysis was performed to determine significant factors for predicting bad outcomes. RESULTS One hundred fifty-nine cases of PCMC, of whom 54.7% were male and 77.2% were white, with mean (SD) age 63.5 (13.2) years, were analyzed. Most had been treated with traditional surgical excision (85.5%), with only 9.4% of cases treated with Mohs surgery. Older (odds ratio [OR], 0.93; P = .04) and Asian (OR, 0.02; P = .01) patients had relatively better postsurgical outcomes. Larger tumors (OR, 6.71; P = .14), those persistent for longer prior to surgery (OR, 1.02; P = .11), and those located on the trunk (OR, 103.24; P = .005) also were associated with poorer outcomes. Limitations included reliance on case report data. CONCLUSIONS AND RELEVANCE: Patient demographic characteristics and tumor-specific features may provide predictive information regarding the risk of postsurgical recurrence and metastasis after treatment of PCMC.

Colorectal cancer in South Africa: a heritable cause suspected in many young black patients.

BACKGROUND: Colorectal carcinoma (CRC) has a low incidence among the black African population. Largely unrecognised in the scientific literature is the fact that a disproportionately large number of young black patients (<50 years old) present with CRC. OBJECTIVES: To analyse those tumours, which we propose may link them to morphological features associated with known genetic pathways. METHODS: A retrospective review of South African patients histologically diagnosed as having CRC by the Division of Anatomical Pathology, National Health Laboratory Service (NHLS) and the University of the Witwatersrand (1732 patients from 1990 to 2003). The histology was fully reviewed in 609 patients (1997-2002), and all specimens from patients <50 years of age were subjected to immunohistochemistry tests for mismatch repair proteins, as well as APC and p53 proteins. RESULTS: Most young patients (<50 years) were black (41% v. 10% white; p < or = 0.001). Blacks had predominantly proximal tumours and significantly more poorly differentiated and/or mucinous tumours (p = 0.006), and loss of mismatch repair protein expression was more evident than in whites. CONCLUSIONS: It seems likely that CRC in young blacks develops through the accumulation of mutations, most probably via mismatch repair deficiency or promoter methylation, which in turn is linked to poor differentiation and a mucinous architecture.

Long-term outcomes and clinicopathologic differences of African-American versus white patients treated with breast conservation therapy for early-stage breast cancer.

BACKGROUND: African-American (AA) and white patients with early-stage disease who were treated with breast conservation therapy (BCT) were examined to detect differences in clinicopathologic features and outcomes as a function of race. METHODS: Clinical data from the charts of 2164 white and 207 AA patients treated with BCT, and p53 expression status on 444 patients (from an existing tissue database), were analyzed to detect differences between the 2 cohorts. RESULTS: The median follow-up was 7 years. There were no differences in the method of tumor detection, lymph nodes excised, surgical margin status, or chemotherapy/radiotherapy delivered, reflecting similar screening and treatment policies for AA women in the study community. Despite this, AA patient presented at a younger age, with higher T and N classifications, and more estrogen and progesterone negative and "triple negative" tumors (all P values < .016). Tumors in AA patients were p53 positive more often than tumors in white patients (P= .0003). At 10 years, AA patients had a higher rate of distant metastasis (20% vs 17%; P= .042), lymph node recurrence (6% vs 2%; P= .004), and breast recurrence (17% vs 13%; P= .036). There was no difference in overall survival between the 2 groups. On multivariate analysis, only lymph node recurrence (risk ratio of 3.140; 95% confidence interval, 1.396-7.063 [P= .0057]) remained significantly higher among AA women. CONCLUSIONS: In this cohort of uniformly treated patients, the authors found the expected clinicopathologic differences, but race was not found to be an independent predictor of local recurrence for AA patients when other confounding variables were taken into account in the multivariate model. These findings suggest that BCT is a reasonable option for appropriately selected AA patients. To the authors' knowledge, this is the largest study addressing outcomes after BCT for AA women published to date.

Inter- and intra-ethnic differences for female breast carcinoma incidence in the continental United States and in the state of Hawaii.

BACKGROUND: Ethnic diversity is well-documented for female breast carcinoma incidence in the continental US but is not so well-established in the state of Hawaii. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) program, we analyzed n=323,607 in situ and invasive female breast cancer cases for major ethnic groups in the continental US and in Hawaii, diagnosed during the years 1992-2002. RESULTS: In the continental US, age-specific incidence rate patterns and prognostic factor profiles were good-risk for Asian or Pacific Islanders (API), intermediate for Whites, and poor-risk for Blacks. For example, early age-at-onset, high nuclear grade, aggressive histopathologic subtypes, and hormone receptor negative expression was associated with Black race in the continental US. In Hawaii, age-specific rate and prognostic profiles were more favorable for API than for White women, albeit not so striking as in the continental US. CONCLUSION: We observed inter- and intra-ethnic differences for female breast carcinoma in the continental US and in the state of Hawaii. While inter-racial disparities were expected, intra-racial differences were somewhat unexpected and possibly due to variations in racial subgroup mixing and/or cultural assimilation. For example, API women with breast carcinoma in the continental US included 96.03% Asians and 2.4% Pacific Islanders. In contrast, API women with breast carcinoma in Hawaii included 76.52% Asians and 23.46% Pacific Islanders. Moreover, APIs were more likely to be first-generation migrants in the continental US ( approximately 92%) than in Hawaii ( approximately 34%). Future studies should attempt to disaggregate racial data to separately characterize epidemiological patterns for individual ethnic groups.

Incidence and survival of mucinous adenocarcinoma of the colorectum: a population-based study from an Asian country.

PURPOSE: Previous studies have shown conflicting results on the prognosis of mucinous adenocarcinoma of the colorectum. This could be because of heavy bias on patient selection. Furthermore, little data are available from Asian populations. This study was designed to examine incident and prognostic characteristics of mucinous adenocarcinoma of the colorectum based on data obtained from a population-based, Asian, cancer registry. METHODS: A total of 627 of 15,762 were mucinous adenocarcinoma cases from invasive colorectal cancer patients registered in the Singapore Registry from 1968 to 1997. Age-standardized incidence rate was used to describe the incident pattern of mucinous adenocarcinoma of colon and rectum during a period of time. Survival of patients with mucinous adenocarcinoma or ordinary adenocarcinoma was compared using relative survival and proportional hazards model. RESULTS: Age-standardized incidence rate of mucinous adenocarcinoma of the colon and rectum were almost unchanged in males, rising slightly in females during the study periods from 1968 to 1972 to 1993 to 1997. The proportion of mucinous adenocarcinoma cases was similar among genders and calendar-year periods but was higher in younger age groups, Malays and Indians, in advanced stages of the disease, and proximal colon. Five-year relative survival rate of patients with mucinous adenocarcinoma were similar in the colon but were lower in the rectum. CONCLUSIONS: Colorectal mucinous adenocarcinoma as a different etiologic entity from other histologic types of colorectal cancer was suggested. Possibly greater aggressiveness of mucinous adenocarcinoma occurring in the rectum requires confirmation but suggests that mucin is important in the pathogenesis of mucinous adenocarcinoma.

Racial/ethnic differences in survival rates in a population-based series of men with breast carcinoma.

BACKGROUND: A rare occurrence, about 1500 men in the United States develop breast carcinoma each year. Little is known about survival patterns at the population level, particularly about racial/ethnic variation. METHODS: Using data from the Surveillance, Epidemiology, and End Results Program, we examined survival rates in 1979 men diagnosed with primary invasive breast carcinoma between 1973 and 1997. Race was defined as non-Hispanic white, non-Hispanic black, and other race/ethnicity (predominantly Asian/Pacific Islander and Hispanic). The two outcomes were all-cause and breast carcinoma- specific mortality. Survival curves were drawn using Kaplan-Meier estimates and Cox regression was used to estimate the risk of death with hazard ratios and 95% confidence intervals. For both outcomes, the racial/ethnic survival curves differed significantly when the log rank test was used. Therefore, separate models were run for each racial/ethnic group. Covariates included age, stage, histology, surgery, radiation therapy, and year of diagnosis. Estrogen and progesterone receptor status were available for 616 men. RESULTS: Survival rates differed significantly by race/ethnicity. Overall, 5-year survival rates were 66% for whites, 57% for blacks, and 75% for men of other race/ethnicity. Blacks presented with more advanced disease. By stage, whites and blacks had worse survival rates compared with men of other race/ethnicity. The effects of prognostic factors such as age, surgery type, and radiation were similar, but not always significant, for all groups. Diagnosis year and estrogen receptor status did not affect survival. CONCLUSIONS: Survival following male breast carcinoma differed by race/ethnicity, whereas the prognostic factors associated with survival were similar.

Alterations in exon 4 of the p53 gene in gastric carcinoma.

BACKGROUND & AIMS: Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4. METHODS: DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion. RESULTS: Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067). CONCLUSIONS: There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.

The incidence of borderline ovarian tumors in Israel: a population-based study.

BACKGROUND: In hospital-based studies, one-eighth of ovarian cancers have been considered borderline ovarian tumors (BOTs). Population-based data regarding the incidence of BOTs are lacking in the international literature. The authors' objectives were to measure the incidence of BOT in Israel and compare rates among ethnic groups (based on ethnic group and country of birth) for the years 1985-1993. METHODS: The authors analyzed data reported to a nationwide cancer registry. Population estimates by subpopulation were derived from census and intercensus estimates, which were based on an updated population registry. RESULTS: The age-adjusted standard rate (ASR) for the entire population was 10.6 per million (95% confidence interval [CI], 9.2-12.0) for the period 1985-1993. Significant differences in ASR were observed among ethnic subgroups, with the lowest incidence among non-Jews (ASR, 5.0 per million; 95% CI, 0.7-9.3) and the highest among new immigrants from the former Soviet Union (FSU) who had been arriving since 1989 (ASR, 22.7 per million; 95% CI: 14.2-31.3). Between the periods 1985-1989 and 1990-1993, the ASR for Jews nearly doubled (rate ratio, 1.86; 95% CI, 1.1-2.5). This near-doubling was influenced, but not wholly accounted for, by the immigration from FSU and was observed in all ethnic subgroups. CONCLUSIONS: The variations in the incidence rates of BOT among ethnic groups may be related to differences in fertility patterns, use of fertility drugs, and genetic predisposition. The pattern of near-doubling in rates may reflect biases caused by increased detection or shifts in the classification of ovarian tumors; if they are real, a biologic explanation is needed.