Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Radiation dose to the brain and subsequent risk of developing brain tumors in pediatric patients undergoing interventional neuroradiology procedures.

Radiation dose to the brain and subsequent lifetime risk of diagnosis of radiation-related brain tumors were estimated for pediatric patients undergoing intracranial embolization. Average dose to the whole brain was calculated using dosimetric data from the Radiation Doses in Interventional Radiology Study for 49 pediatric patients who underwent neuroradiological procedures, and lifetime risk of developing radiation-related brain tumors was estimated using published algorithms based on A-bomb survivor data. The distribution of absorbed dose within the brain can vary significantly depending on field size and movement during procedures. Depending on the exposure conditions and age of the patient, organ-averaged brain dose was estimated to vary from 6 to 1600 mGy. The lifetime risk of brain tumor diagnosis was estimated to be increased over the normal background rates (57 cases per 10,000) by 3 to 40% depending on the dose received, age at exposure, and gender. While significant uncertainties are associated with these estimates, we have quantified the range of possible dose and propagated the uncertainty to derive a credible range of estimated lifetime risk for each subject. Collimation and limiting fluoroscopy time and dose rate are the most effective means to minimize dose and risk of future induction of radiation-related tumors.

Ultrasound-detected thyroid nodule prevalence and radiation dose from fallout.

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

[No convincing evidence for a causal relationship between childhood nasopharyngeal radium irradiation and head-neck tumors or hormone-related disorders later in life; a retrospective cohort study]. / Geen overtuigend bewijs voor een causaal verband tussen nasofaryngeale radiumbestraling op de kinderleeftijd en latere hoofd-halstumoren en hormonale aandoeningen; een historisch cohortonderzoek.

OBJECTIVE: To study the risk of malignant and benign tumours and hormone-related disorders among patients treated with nasopharyngeal radium irradiation for hypertrophic adenoid or hearing loss caused by otitis media serosa. DESIGN: Retrospective cohort study. METHOD: The medical record registries of 9 hospitals were used to identify a radium-exposed group (n = 5358) and a control group of unexposed patients (n = 5265), who were treated by an otolaryngologist in the period 1945-1981. The vital status of the subjects was determined using municipal resident registries, and the cause of death of decedents was retrieved from Statistics Netherlands (1950-1997). The data was also coupled with the Netherlands Cancer Registry (1989-1996). For the subjects still alive in 1997, the prevalence of relevant disorders was determined using a self-administered questionnaire and disorders reported by the participants were medically verified. The risk of disease in the radium group was then compared with that of the control group. RESULTS: The average radiation doses were 2.75, 0.109 and 0.015 Gy for nasopharynx, pituitary, and thyroid, respectively. There was no statistically significantly elevated risk for malignancies of the head and neck area (radium-exposed group; n = 14; control group: n = 11 (relative risk (RR): 1.2; 95% CI: 0.6-2.8)). Four of the five thyroid carcinomas were found in the radium-exposed group (RR: 3.8; 0.5-76). Elevated risks were observed for breast cancer (RR: 1.6; 0.9-2.7) and non-Hodgkin's lymphoma (RR: 2.7; 1.0-8.7). There was an increased risk for skin basal cell carcinoma (BCC) of the head and neck (odds ratio (OR): 2.6; 1.0-6.7), but the risk of BCC of other body parts was lower (OR: 0.3; 0.1-1.3). There were no major differences between radium and control subjects with respect to benign head and neck tumours (OR: 1.0; 0.5-1.7) or hormonal disorders. Exposed men reported slightly more fertility disorders than men in the control group (OR: 1.4; 1.0-2.1), but there was no clear dose-response relationship. CONCLUSION: After a mean follow-up of 31 years, there was no strong evidence for an elevated risk of head and neck tumours or hormone-related disorders in adulthood among subjects who had been treated with nasopharyngeal radium irradiation during childhood.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study.

BACKGROUND: Nasopharyngeal radium irradiation (NRI) was used widely from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. METHODS: We conducted a retrospective cohort study of all-cause and cancer-related mortality in 5358 NRI-exposed subjects and in 5265 frequency-matched nonexposed subjects, who as children were treated at nine ear, nose, and throat clinics in The Netherlands from 1945 through 1981. We recorded personal and medical data from original patient medical records and assessed vital status through follow-up at municipal population registries. Risk of mortality was evaluated by standardized mortality ratios (SMRs). All statistical tests were two-sided. RESULTS: The average radiation doses were 275, 10.9, 1.8, and 1.5 cGy for the nasopharynx, pituitary, brain, and thyroid, respectively. The median follow-up was 31.6 years. Three hundred two NRI-exposed subjects had died, with 269.2 deaths expected (SMR = 1.1; 95% confidence interval [CI] = 1.0 to 1.3); among nonexposed subjects, 315 died, with 283.5 deaths expected (SMR = 1.1; 95% CI = 0.99 to 1.2). Cancer-related deaths of 96 exposed subjects (SMR = 1.2; 95% CI = 0.95 to 1.4) and 87 nonexposed subjects (SMR = 1.0; 95% CI = 0.8 to 1.3) were documented. There were no excess deaths from cancers of the head and neck area among exposed subjects. However, there were excess deaths from cancers of lymphoproliferative and hematopoietic origin (SMR = 1.9; 95% CI = 1.1 to 3.0), mainly from non-Hodgkin's lymphoma (SMR = 2.6; 95% CI = 1.0 to 5.3). We found no evidence that breast cancer deaths were less than expected (SMR = 1.7; 95% CI = 0.9 to 2.8) in contrast to an earlier study. CONCLUSIONS: Our findings do not indicate an increased cancer mortality risk in a population exposed to NRI in childhood. More prolonged follow-up of this and other NRI cohorts is recommended.

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Breast cancer mortality after diagnostic radiography: findings from the U.S. Scoliosis Cohort Study.

STUDY DESIGN: A retrospective cohort study was conducted in 5573 female patients with scoliosis who were referred for treatment at 14 orthopedic medical centers in the United States. Patients were less than 20 years of age at diagnosis which occurred between 1912 and 1965. OBJECTIVES: To evaluate patterns in breast cancer mortality among women with scoliosis, with special emphasis on risk associated with diagnostic radiograph exposures. SUMMARY OF BACKGROUND DATA: A pilot study of 1030 women with scoliosis revealed a nearly twofold statistically significant increased risk for incident breast cancer. Although based on only 11 cases, findings were consistent with radiation as a causative factor. METHODS: Medical records were reviewed for information on personal characteristics and scoliosis history. Diagnostic radiograph exposures were tabulated based on review of radiographs, radiology reports in the medical records, radiograph jackets, and radiology log books. Radiation doses were estimated for individual examinations. The mortality rate of the cohort through January 1, 1997, was determined by using state and national vital statistics records and was compared with that of women in the general U. S. population. RESULTS: Nearly 138,000 radiographic examinations were recorded. The average number of examinations per patient was 24.7 (range, 0-618); mean estimated cumulative radiation dose to the breast was 10.8 cGy (range, 0-170). After excluding patients with missing information, 5466 patients were included in breast cancer mortality analyses. Their mean age at diagnosis was 10.6 years and average length of follow-up was 40.1 years. There were 77 breast cancer deaths observed compared with the 45.6 deaths expected on the basis of U.S. mortality rates (standardized mortality ratio [SMR] = 1.69; 95% confidence interval [CI] = 1.3-2.1). Risk increased significantly with increasing number of radiograph exposures and with cumulative radiation dose. The unadjusted excess relative risk per Gy was 5.4 (95% CI = 1.2-14.1); when analyses were restricted to patients who had undergone at least one radiographic examination, the risk estimate was 2.7 (95% CI = -0. 2-9.3). CONCLUSIONS: These data suggest that exposure to multiple diagnostic radiographic examinations during childhood and adolescence may increase the risk of breast cancer among women with scoliosis; however, potential confounding between radiation dose and severity of disease and thus with reproductive history may explain some of the increased risk observed.

A prospective study of estradiol and breast cancer in Japanese women.

Few studies have prospectively examined endogenous hormone levels as risk factors for breast cancer. The present study compares prediagnostic hormone levels using stored serum from breast cancer cases and controls selected from the Life Span Study population of the Radiation Effects Research Foundation in Hiroshima and Nagasaki, Japan. Stored serum samples collected in 1968-1970 were assayed for 72 women subsequently diagnosed with breast cancer and 150 control subjects in 72 case-control sets matched on age, date of blood collection, exposure, radiation dose, and city. Serum levels were determined for sex hormone binding globulin, total estradiol (E2), bioavailable E2, dehydroepiandrosterone sulfate, and prolactin. Matched case-control comparisons of hormone levels were carried out by conditional logistic regression and were adjusted for menopausal status at the time of blood drawing. The odds ratio per unit log change in bioavailable E2 was 2.2 [95% confidence interval (CI), 1.02-5.31 for all subjects, and 2.3 (95% CI, 0.55-6.8) and 2.1 (95% CI, 0.55-9.7), respectively, based only on premenopausal or postmenopausal serum. The estimated odds ratios in each quintile of bioavailable E2 level, using the lowest quintile as referent, were 1.00, 1.89, 1.43, 3.45, and 3.37 (P for trend = 0.035). For sex hormone binding globulin, the overall odds ratio was 0.58 (95% CI, 0.14-2.26), and 1.00 (95% CI, 0.19-5.45) and 0.21 (95% CI, 0.02-1.88) based on premenopausal and postmenopausal serum, respectively. This study offers further prospective support for the hypothesis that a high level of biologically available E2 is a risk factor for the subsequent development of breast cancer.

Epstein-Barr virus involvement in gastric cancer: biomarker for lymph node metastasis.

EBV involvement in gastric cancer is characterized by episomal monoclonality, high antibody titers, EBV encoded small RNA and EBV nuclear antigen 1 expression in all tumor cells, and in the intramucosal stage, by a unique morphology. EBV involvement varies by population (approximately 7% of gastric cancers in Japan and >15% in Western countries), sex, histological type, and tumor location. The present study compares frequency of lymph node metastasis (LNM) between 170 EBV-positive and 1590 EBV-negative gastric cancer cases in Japan by level of invasiveness. Frequency of LNM increased with increasing depth of invasiveness but was consistently and significantly greater for EBV-negative cases (P = 0.0018). In particular, there were no instances of LNM among 75 EBV-positive cases as compared with 53 among 562 EBV-negative cases restricted to the mucosa and submucosa (odds ratio, 0; 95% confidence limits, 0-0.20). The finding suggests that genetic control of metastasis may differ between EBV-related and other gastric cancers. Also, the possibility that EBV-positive, noninvasive gastric cancers may not require lymph node dissection suggests that routine assay of biopsy specimens for EBV involvement could be important in populations, like that of Japan, where early gastric cancers are seen frequently.

Epstein-Barr-virus-associated gastric cancer in Russia.

The present investigation was carried out to estimate the prevalence of EBV-associated cases among gastric carcinoma (GC) patients of Russia and the Republics of the former Soviet Union (FSU). With this aim, formalin-fixed paraffin-embedded blocks from 206 gastric carcinomas obtained from patients of the Cancer Research Center, Moscow, were investigated by EBV-encoded RNA-1 (EBER-1) in situ hybridization applied to paraffin sections. As a result, 18 GC cases (8.7%) revealed uniform EBER-1 expression restricted to the carcinoma cells. Hybridized signals not detected in non-neoplastic gastric epithelium. EBV involvement was significantly more frequent among males, especially in tumors of less differentiated types (moderately differentiated tubular adenocarcinomas and poorly differentiated solid adenocarcinomas) and located in the upper stomach (cardia and middle). Most EBV-positive GCs were characterized by strong lymphoid-compartment involvement. Our findings concerning the distribution of EBV-positive GCs by sex, site and hystological type are similar to those in Japan, however, EBV-positive rate of GC cases in Russia is higher than in Japan and lower than in USA.

Morphological characteristics of Epstein-Barr virus-related early gastric carcinoma: a case-control study.

A strong association between Epstein-Barr virus (EBV) and gastric carcinoma has been demonstrated by the uniform presence of EBV in all carcinoma cells, episomal monoclonality, elevated antibodies, and a unique 'lace pattern' in the mucosa. The present study is concerned with morphological changes of intramucosal carcinoma and submucosal invasion, reactive lymphocytes, and with atrophy and intestinal metaplasia of the surrounding mucosa. Fifty-two EBV-positive early gastric carcinomas were matched by age, sex, and site of tumor with 103 EBV-negative carcinomas, all of which had previously been examined by serial cut-sections of the tumors and surrounding mucosa. Epstein-Barr virus involvement was strongly associated with lace pattern morphology as demonstrated previously, and with lymphocytic infiltration in and around the tumor nests in the mucosa. The infiltrating lymphocytes in the tumor nests were mainly composed of CD8+ T lymphocytes. Lymphoepithelioma (LE)-like carcinoma, was observed in the submucosal portions of 13 of 31 EBV-positive cases with such invasions, including 12 of 29 with lace pattern morphology in the mucosa. The majority of the surrounding gastric mucosa showed moderate to severe atrophy with marked depletion of parietal cells, complete-type intestinal metaplasia in EBV-positive cases, and Helicobacter pylori (H. pylori) infection for both EBV-positive and EBV-negative cases. It is suggested that EBV infection may occur in the atrophic gastric epithelial cells associated with intestinal metaplasia and H. pylori infection, leading to the development of carcinoma. Such cancers show lace pattern and marked lymphocytic reaction in the mucosa, with some tendency for histological change and lymphocytic reaction during the invasive process without lymph node metastasis.

Salivary gland tumors among atomic bomb survivors, 1950-1987.

BACKGROUND: Malignant and benign tumors of the salivary glands have been associated with exposure to ionizing radiation from various sources, including the atomic bombings in Hiroshima and Nagasaki. However, questions remain unanswered regarding the nature and size of the risk and specific types of tumors involved. METHODS: The incidence and pathology of malignant and benign tumors of the salivary glands was studied in the Life Span Study cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation (RERF) in Hiroshima and Nagasaki, Japan. Incident cases diagnosed during the period 1950-1987 were ascertained from the tumor and tissue registries of Hiroshima and Nagasaki and supplemented by additional case findings from autopsy, biopsy, and surgical specimens maintained at RERF and other institutions. Pathology slides and medical documents were reviewed by a panel of four pathologists who classified tumors using the World Health Organization classification scheme. Analyses were performed of histologic features associated with radiation exposure. RESULTS: Of 145 tumors of the salivary glands identified (119 of the major and 26 of the minor salivary glands), 120 (83%) were histologically confirmed by the current investigators. Among 41 malignant tumors, the frequency of mucoepidermoid tumor was disproportionately high at high radiation doses (P = 0.04); among 94 benign tumors, the frequency of Warthin's tumor increased with increasing radiation dose (P = 0.06). The nature of the tumor was undetermined for the remaining ten cases. Mortality from malignant tumors of the salivary gland was inversely related to radiation dose, reflecting the predominance of mucoepidermoid carcinoma at high dose levels in this series. In one case with high radiation exposure, mucoepidermoid carcinoma of the parotid gland was accompanied by a preexisting or coexisting Warthin's tumor. CONCLUSIONS: These findings, supported by population-based analyses in a companion study reported elsewhere, suggest a causal role for ionizing radiation in salivary gland tumorigenesis, particularly for mucoepidermoid carcinoma, and in the induction of one type of benign tumor (Warthin's tumor).

Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk.

A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR1Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR1Sv = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR1Sv = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR1Sv = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR1Sv = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study.

Studies of cancer and radiation dose among atomic bomb survivors. The example of breast cancer.

A comprehensive program of medical follow-up of survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, by the Radiation Effects Research Foundation (RERF) has produced quantitative estimates of cancer risk from exposure to ionizing radiation. For breast cancer in women, in particular, the strength of the radiation dose response and the generally low level of population risk in the absence of radiation exposure have led to a clear description of excess risk and its variation by age at exposure and over time following exposure. Comparisons of RERF data with data from medically irradiated populations have yielded additional information on the influence of population and underlying breast cancer rates on radiation-related risk. Epidemiological investigations of breast cancer cases and matched controls among atomic bomb survivors have clarified the role of reproductive history as a modifier of the carcinogenic effects of radiation exposure. Finally, a pattern of radiation-related risk by attained age among the survivors exposed during childhood or adolescence suggests the possible existence of a radiation-susceptible subgroup. The hypothetical existence of such a group is lent plausibility by the results of recent family studies suggesting that heritable mutations in certain genes are associated with familial aggregations of breast cancer. The recent isolation and cloning of one such gene, BRCA1, makes it likely that the hypothesis can be tested using molecular assays of archival and other tissue obtained from atomic bomb survivor cases and controls.

A unique morphology of Epstein-Barr virus-related early gastric carcinoma.

Epstein-Barr virus (EBV) involvement in gastric cancer is demonstrated by uniform presence of viral RNA in carcinoma cells as detected by EBV-encoded small RNA in situ hybridization, monoclonal proliferation of EBV-infected carcinoma cells, and elevated antibodies. Our review of selected early gastric cancers found that 46 of 49 EBV-positive lesions (94%) but only four of 97 EBV-negative lesions (4%) conformed to a unique morphology, in which carcinoma cells formed lace patterns of branching and/or anastomosing structures with lymphocytic infiltration in and around the carcinoma nests in the mucosa. We conclude that EBV-related gastric carcinoma has a distinct and characteristic morphology in the early stage of development, and this lace pattern is a biomarker of EBV involvement in early gastric cancer.

Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan.

Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.

Epstein-Barr virus and gastric remnant cancer.

BACKGROUND: Carcinoma arising in the gastric remnant many years after partial gastrectomy for benign disease, referred to as gastric remnant cancer (GRC) is well known, and many causal explanations have been proposed. Elsewhere, Epstein-Barr virus (EBV) involvement has been demonstrated in a small but significant fraction of gastric cancers, and evidence has been presented suggesting that, in positive cases, EBV may have played a causal role. The present report is concerned with EBV involvement in GRC in particular. METHODS: Paraffin sections from 48 cases of GRC were studied by EBER-1 in situ hybridization. RESULTS: Thirteen cases (27.1%) showed uniform hybridized signals restricted to the carcinoma cells in contrast to no hybridization in the normal mucosa, intestinal metaplasia, or hyperplastic epithelium. The prevalence of EBV involvement in GRC was significantly higher (P < 0.0001) than in gastric carcinomas from 1825 nonremnant cases; the difference remained highly significant even when the comparison was restricted to nonremnant cancers arising in the cardia and middle stomach, for which EBV-positive rates were highest. CONCLUSION: The EBV may play an important role in the carcinogenesis of GRC.

Incidence of female breast cancer among atomic bomb survivors, 1950-1985.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.