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In Japan in October 2016, the Pharmaceuticals and Medical Devices Agency (PMDA) began to receive electronic data in new drug applications (NDAs). These electronic data are useful to conduct regulatory assessment of sponsors' submissions and contribute to the PMDA's research. In this article, we summarize the number of submissions of quantitative modeling and simulation (M&S) documents in NDAs in Japan, and we describe our current thinking and activities about quantitative M&S in PMDA.

In a study of 7498 American men of Japanese ancestry in Hawaii, 26 incident cases of leukemia or non-Hodgkin's lymphoma were identified after a follow-up period of 19 years. Two of the cases, who were brothers, were diagnosed with adult T-cell leukemia/lymphoma (ATL). Both of these brothers had human T-cell lymphotropic virus type I (HTLV-I) antibodies in their stored serum which were obtained 4 and 18 years before diagnosis. None of the 24 patients with other hematologic malignancies or the 26 matched controls were HTLV-I antibody positive. This finding lends further support for a role of HTLV-I in the etiology of adult T-cell leukemia/lymphoma.

Aims : A substantial minority of intestinal metaplasia (IM)-associated stomach cancers express a gastric product—pepsinogen group II (PGII). The aim of this study was to examine PGII expression as it relates to IM and to tumour heterogeneity. Methods and results : The extent of IM was divided into four levels: none, minimal, moderate, extensive. Stomach specimens (N = 165) were stained for PGII and two tumour markers, epidermal growth factor receptor (EGFr) and p53. PGII was more likely to be expressed with moderate or extensive IM than with minimal or no IM (P = 0.05). Cancers that expressed PGII were more likely to be of high stage than those that did not (P = 0.035). Of 25 cases that expressed all three markers (PGII, EGFr, p53), 20 (80%) had stage 3 or 4 disease, compared with 11 (37%) advanced cancers expressing none of the markers (P = 0.001). Cancers expressing one or two markers were between these extremes. Conclusions : PGII+ cancers in IM-associated gastric cancers may derive from residual gastric glands, or may arise from postinduction reversion to a gastric phenotype from intestinalized cells. This is supported by the more frequent association of PGII expression with the most extensive degrees of IM and its association with high-stage cancers that display heterogeneity in tumour marker expression.

Objectives: To describe trends in BMI among different ethnic groups in Hawaii and to explore the relation of nutrient and food intake with excess weight. Research Methods and Procedures: We pooled demographic, anthropometric, and nutritional data derived from a detailed diet history for 159, 683 participants of 18 population-based epidemiological studies conducted in Hawaii over a 25-year period. The age-adjusted prevalence of excess weight (BMI ≥ 25 kg/m2) was estimated for 5-year intervals. To explore dietary determinants of excess weight, we computed odds ratios using logistic regression. Results: During the study period, the prevalence of excess weight increased considerably among all ethnic groups. Native Hawaiians had the highest and Asian Americans had the lowest prevalence of excess weight at all times. Although the percentage of calories consumed from carbohydrates increased, the percentage of calories from fat decreased over time. On an individual level, fat and protein consumption predicted a higher BMI, and dietary fiber intake predicted a lower BMI. Similarly, a higher consumption of meat, poultry, and fish was related to excess weight, whereas fruit and vegetable intake were inversely associated with excess weight. After stratification by ethnicity, the associations were not materially altered among women, but carbohydrates seemed to have a stronger association with excess weight among Native Hawaiian and Japanese men than among white men. Discussion: In this large ethnically diverse population, plant-based foods and dietary fiber emerged as a potential protective factor against excess weight regardless of ethnicity.

The selective lateral growth of GaN with extremely low dislocation density has been achieved for the first time directly on a masked sapphire substrate without a GaN epitaxial underlayer via metalorganic vapor phase epitaxy. Both the mask material for selective growth and the growth conditions have been optimized for this complete selective growth. Dislocation densities less than 5 × 106 cm−2 have been obtained when SiN was used as a mask and GaN was used as a low-temperature buffer layer. This reduction in threading dislocation density results from bending the threading dislocations toward the facet surfaces, which has been confirmed by cross-sectional transmission electron microscopy observations. This growth technique is very promising for practical device production, such as that for blue laser diodes, because a complete device structure with extremely low dislocation density can be grown by a single growth process. (© 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

OBJECTIVES. To assess the pathology of gastric carcinoma and to determine whether carcinoma of the cardia occurs more often among whites than among other ethnic groups in Hawaii. This study focuses on demographic differences in subsite locations and histologic types of gastric carcinoma. METHODS. We reviewed 532 sequential gastric carcinomas accessioned between 1993 and 1999 in the Hawaii Tumor Registry. Pathology reports and slides were reviewed by the study pathologist. RESULTS. Carcinoma of the cardia occurred in 51 (15.8%) of 323 males compared with 18 (8.6%) of 209 females (P = 0.02, after age adjustment). The age-adjusted percent of cardia cases was 41.8% for Hawaiian white males compared with 13.4% for men of all other ethnic groups (P = 0.0002). The age-adjusted percent of cardia cases was 22.4% for Hawaiian white females compared with 7.3% for females of other groups. (P = 0.08). At all age levels, females had more frequent diffuse carcinomas and less frequent intestinal type gastric carcinomas than men. The age-adjusted percent with diffuse carcinoma was 35.3% for females and 13.7% for males (P < 0.0001). Also, the sex-adjusted percent with diffuse carcinoma was 26.0% for patients younger than 75 years of age compared with 17.0% for patients 75 years or older (P = 0.01). Conversely, the sex-adjusted percent with intestinal carcinoma was 67.9% for patients younger than 75 years of age compared with 77.1% for patients 75 years or older (P = 0.02). The proportion of cases showing precursor lesions (intestinal metaplasia or superficial gastritis) increased progressively with the distance of the carcinoma from the cardia. CONCLUSIONS. Carcinoma of the cardia is predominantly a tumor of white males and is not associated with the multifocal gastritis characteristically found with carcinoma distal to the cardia. Diffuse gastric carcinoma shows no ethnic predilection, but expression of this phenotype is clearly related to the age and gender of the patient.

Microwave polymerization was used to make composite resin inlays and the effect examined of the concentration of polymerization initiator for the base monomer. The monomers used were 2,2-bis [4-(3-methacriloxy-2-hydroxypropoxy) phenyl] propane (Bis-GMA) and triethyleneglycol dimethacrylate (TEGDMA). Bis-GMA and TEGDMA were mixed in a ratio of 6:4 by weight and were separated into five groups. To each group was added benzoyl peroxide (BPO) in the ratios of 0.1, 0.3, 0.5, 0.7 and 0.9 wt% as the polymerization initiator. These were used as the base monomers. The results showed that the degree of conversion of the cured sample increased with increasing concentration of BPO from 0.1 to 0.5 wt%, however there was no significant difference at 0.5, 0.7 and 0.9 wt% (P> 0.01). Compression strength, diametral tensile strength and the Knoop hardness showed a similar tendency as the degree of conversion. No significant difference was recorded in the Knoop hardness between the top and the bottom surfaces (P> 0.01), which suggested a uniform polymerization in the cured sample. Thus, microwave polymerization would be an efficacious method for making resin inlays with the addition of BPO to the base monomer (Bis-GMA:TEGDMA, 6:4). The maximum conversion was found at a concentration of 0.5 wt%.

We visualized neural activity evoked by stimulating Schaffer collaterals in the CA1 regions in a rat hippocampal slice preparation, and anlayzed the effect of exposure to an ischemia-like condition at room temperature. We recorded also field potentials from the nearby pyramidal cell layer. Optical signals revealed propagation of action potentials in the molecular/radiatum layers in both directions from the stimulated site, followed by activation of pyramidal/oriens layers, and at the later phase spread to more lateral regions. In an ischemia-like condition in which oxygen and glucose were removed from the perfusing fluid, population spikes and/or slow potentials gradually reduced and disappeared, while optical signals remained only at the stimulation locus. When the perfusate solution was switched to the normal fluid within 10 min population spikes and the optical signals restored to the control level after 15-30 min. These observations demonstrated that generation of neural activities in Schaffer collaterals are the most resistive, but that synaptic transmissions are very sensitive to ischemia-like condition.

The water activity (aw) of microbial substrates, biological samples, and foods and drinks is usually determined by direct measurement of the equilibrium relative humidity above a sample. However, these materials can contain ethanol, which disrupts the operation of humidity sensors. Previously, an indirect and problematic technique based on freezing-point depression measurements was needed to calculate the aw when ethanol was present. We now describe a rapid and accurate method to determine the aw of ethanol-containing samples at ambient temperatures. Disruption of sensor measurements was minimized by using a newly developed, alcohol-resistant humidity sensor fitted with an alcohol filter. Linear equations were derived from aw measurements of standard ethanol-water mixtures, and from Norrish's equation, to correct sensor measurements. To our knowledge, this is the first time that electronic sensors have been used to determine the aw of ethanol-containing samples. Copyright 1999 John Wiley & Sons, Inc.

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.

Although some lymphatic plexuses exist in lower quadrants of the breast, there have been no investigations of whether or not carcinoma located in this region is a prognostic factor for breast cancer. Of 914 patients with carcinoma of the breast who underwent curative resection following chemo-endocrine therapy between 1982 and 1985, 149 patients had disease of the lower quadrants. The recurrence-free survival rate was lower in patients with the lower quadrants carcinoma than in those with carcinoma of other breast regions. Multivariate analysis showed that a lower quadrant tumor location was a significant prognostic factor for recurrence, especially soft tissue and visceral recurrence. The worse prognosis of patients with lower quadrant carcinoma of the breast suggests the possible existence of residual or occult tumor cells after surgical resection.

The incidence rate of gastric cancer among men of Japanese ancestry living in Hawaii is about one-third as high as that of their counterparts living in Japan. Because of this difference, a prospective study was conducted to identify factors related to the development of gastric cancer in Hawaii. Eight thousand and six (8,006) men born from 1900-1919 were examined from 1965 to 1968 and followed for over 25 years. During this time, 250 incident cases of gastric cancer were identified. The study has found the following : 1) prior infection with Helicobacter pylori bacteria increased the risk for stomach cancer ; 2) cigarette smoking was positively associated with gastric cancer with age at which smoking started being an important risk factor ; 3) after taking cigarette smoking into account, alcohol intake was not related to stomach cancer risk ; 4) a low pepsinogen I level identified subjects at increased risk for the intestinal histologic type of gastric cancer ; 5) a low serum ferritin level was a marker for increased risk of stomach cancer ; 6) there was a weak indication that the intake of vegetables and fruits was inversely related to gastric cancer ; 7) there was no association of stomach cancer with levels of serum cholesterol, serum uric acid, serum micronutrients (retinol, β-carotene or α-tocopherol) or blood hematocrit ; 8) there was also no association of gastric cancer with body mass index or physical activity.

Latent carcinomas of the prostate, discovered at autopsy in men with no prior treatment for prostatic disease, were studied for ras proto-oncogene mutations. Subjects included 21 Japanese, 15 U.S. whites, 15 U.S. blacks, 20 Hawaiian Japanese and 10 Colombians. PCR and sequence-specific oligonucleotide hybridization identified mutations in 5 Japanese, in 1 Hawaiian Japanese, in 1 U.S. black, in 1 U.S. white and in 3 Colombians. The 5 Japanese tumor samples contained 3 point mutations in codon 12 of K-ras and 2 mutations in codon 12 of N-ras respectively. One tumor in a Hawaiian Japanese man also showed a K-ras point mutation at codon 12. Two Colombians and one U.S. black man had tumors with mutations at codon 61 of H-ras, while 1 Colombian showed an N-ras mutation at this codon. The overall frequency of ras gene mutations was low, but point mutations in codon 12 were most common in latent tumors of Japanese, who experienced the lowest incidence and mortality from this tumor. Latent tumors in men from ethnic groups with high mortality and incidence rates showed fewer ras mutations than the Japanese, and these were more likely to involve codon 61. This finding is consistent with prior studies of more aggressive clinical cancers in Japanese men that indicated a higher frequency of mutations at codon 61.

Objective To investigate the effect of recombinant α2binterferon therapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in the peripheral blood in patients with renal cell carcinoma who had undergone radical nephrectomy. Patients and methods Between January 1988 and June 1989, 20 patients (14 men and six women, mean age 59 years, range 43–80) received interferon (IFN) therapy following radical nephrectomy for renal cell carcinoma. Thirteen patients had stage I disease, one had stage II and six had stage III; none had metastases. Results There was a significant increase in NK activity at 5 and 7 months after starting IFN therapy but there was no increase in ADCC. Conclusions Low doses of IFN administered long-term increased NK activity in patients with renal cell carcinoma. This finding should be helpful in designating protocols for randomized studies of post-operative IFN administration as adjuvant therapy.

The association of alcohol, diet, and other lifestyle factors with obstructive uropathy was investigated in a cohort of 6581 Japanese-American men, examined and interviewed from 1971 to 1975 in Hawaii. By studying this migrant population with its heterogeneous exposures, it increases the probabilities of identifying potential risk factors of this prostate disorder. After 17 years of follow-up, 846 incident cases of surgically treated obstructive uropathy were diagnosed with benign prostatic hyperplasia. Total alcohol intake was inversely associated with obstructive uropathy (P < 0.0001). The relative risk was 0.64 (95% confidence interval: 0.52-0.78) for men drinking at least 25 ounces of alcohol per month compared with nondrinkers. Among the 4 sources of alcohol, a significant inverse association was present for beer, wine, and sake, but not for spirits. Buddhist (vs. other) religion, rural (vs. urban) birthplace, and the presence of prostate symptoms were each associated with increased risk of obstructive uropathy, but no association was found with education, number of marriages, or cigarette smoking. Increased beef intake was weakly related to an increased risk (P = 0.047), while no association was found with the consumption of 32 other food items in the study.

BACKGROUND Adenocarcinoma of the small intestine is uncommon. The Hawaii Tumor Registry (HTR) has identified 49 of these tumors since 1960, and the Japan-Hawaii Cancer Study (JHCS) has identified only four of these tumors among a cohort of 8006 Hawaiian-Japanese men followed up for a period of 22 years. Each of the four men reported by the JHCS had multicentric gastrointestinal cancers. METHODS Newly diagnosed cancers are recorded separately by the HTR and JHCS, and linkage is maintained between the two files. Family histories are available from the JHCS, and these are supplemented by a state population file maintained by the Department of Genetics, University of Hawaii. RESULTS Five men, all Japanese, were found to have carcinoma of the proximal small intestine. Each had multicentric carcinomas of the gastrointestinal tract. Carcinoma of the stomach and colon was found in the primary relatives of each of four men whose families lived in Hawaii. CONCLUSIONS The familial clustering of uncommon neoplasms (small bowel carcinoma and multicentric large bowel carcinoma), and the concurrence of gastric and colonic carcinoma suggests that these subjects have a genetic trait that increases susceptibility to a broad range of carcinogens.

Inorganic fillers in seven visible-light (VL)-cured dental composite resins were examined for their size, composition, phase and content, employing the following analytical instruments. SEM observations indicated that five samples could be classified into the hybrid type while the remaining two belonged to micro-filled and sub-micron types. EDX analyses revealed that five samples contained BaO while others lacked BaO. XRD analyses showed that three were in vitreous phase, two were in the crystalline phase and two were mixtures of both. DTG thermal analyses indicated that the hybrid type composites had the higher inorganic filler content (wt%) than the composites of two other types. In conclusion, wide varieties exist in the inorganic fillers in VL-cured dental composite resins currently utilized.

This dietary study was based on 195 male and 66 female cases of lower urinary tract cancer, identified in Hawaii between 1977 and 1986. Each case was matched for sex, age, and ethnic group (Caucasian or Japanese) to 2 population-based controls. There was a decrease in risk with increasing levels of consumption of vitamin C in women (p = 0.03) and dark green vegetables in men (p = 0.02). When examined by quartile, the odds ratios for the highest quartile of intake compared to the lowest quartile were 0.4 for women and 0.6 for men, respectively. Although dark green vegetables are a source of carotenoids, the intake of total carotenoids, retinol and total vitamin A was weakly and inconsistently related to risk in both sexes. Among women only, there was also an inverse association with the consumption of regular ground coffee (p = 0.02) but not with other types of coffee. Finally, there were no statistically significant or consistent differences between cases and controls in the intake of artificial sweeteners and tea.

Cadaverine and pipecolic acid metabolism was investigated in vitro in several organs of the mouse by measuring 14CO2 formation from labeled precursors. The liver showed the highest formation of 14CO2 from [1,5-14C]-cadaverine, whereas brain demonstrated a much lower formation. Anaerobiosis or inhibition of monoamineoxidase (MAO) activity significantly reduced 14CO2 formation in every organ, but inhibition of diamine oxidase (DAO) activity had no effect in brain and kidney. Piperidine was formed from cadaverine in vitro only in the large intestine and its content. This formation is probably of bacterial origin. Under a variety of experimental conditions we were unable to demonstrate any formation of piperidine in brain from cadaverine. Biosynthesis in vitro of [3H]-piperidine from D,L-[3H]-pipecolic acid was very low in brain and kidney. With the exception of brain and kidney, no other organs showed any formation of [3H]-piperidine. Neither MAO nor DAO inhibition influenced [3H]-piperidine formation in the large intestine with its content. Following 1 hr incubation at 37 degrees C under aerobic conditions, the levels of [14C]-pipecolic acid and [3H]-piperidine recovered from mouse brain homogenate did not indicate any significant degradation of these two substances. Our results suggest that under in vitro conditions, cadaverine is not a precursor of piperidine in brain, liver, heart, and kidney and that only very low levels of piperidine can be formed from pipecolic acid in brain. Outside the brain, formation of piperidine from pipecolic acid is detectable only in kidney and in the content of the large intestine. The latter is probably of bacterial origin. Our results do not support previous findings from other authors on an endogenous origin of piperidine in brain from cadaverine and pipecolic acid, and they suggest that a) cadaverine is not a precursor of piperidine in brain, b) the conversion of pipecolic acid into piperidine in the brain does not constitute a major metabolic pathway, and c) the main source of piperidine in the CNS may be of nonneural origin.

A pathology review of breast cancers in Japanese and Caucasian women indicates more numerous in situ carcinomas in the Japanese. Carcinomas with uniform nuclei were also more numerous among Japanese. Japanese women showed more extensive lymphocytic infiltrates adjacent to their tumors than did Caucasian women, and also showed more conspicuous sinus histiocytosis in tumor-free lymph nodes. Fewer Japanese women had lymph node metastases and those with metastases were less likely to have three or more nodes involved. Of these differences only those relating to local invasion, nuclear grade, lymphocytic infiltration, and sinus histiocytosis were statistically significant, but the demonstrated differences are internally consistent with differences in breast cancer incidence and mortality in the two races. Since the two races share the same medical care system and similar environments, the basis of these differences is probably a genetic modulation of hormonal balance and/or immunologic response.

In this nested case-control study, 8,006 American Japanese men were examined and interviewed with a dietary questionnaire from 1965 to 1968. After a follow-up period of over 16 years, 102 colon and 60 rectal cancer incident cases were identified. Dietary data from these patients and from 361 cancer-free controls were analyzed for intake of dietary fiber (DF), vitamins, minerals, macronutrients, and selected food groups. We found a significant (p = 0.042) negative association of DF and colon cancer risk among low fat intake men (less than 61 g/d). In this subgroup, the men consuming less than 7.5 g/d of DF had an adjusted relative risk (RR) for colon cancer of 2.28 (95% CI 0.93-5.60), compared to those consuming greater than or equal to 14.8 g/d of DF. We also observed (among the complete group of subjects) a significant (p = 0.011) negative association between vitamin C intake and the risk of colon cancer. Men in the lowest quintile of vitamin C intake (less than 37 mg/d) had an adjusted colon cancer RR of 1.87 (95% CI 1.03-3.37), compared to men in the highest quintile (greater than or equal to 160 mg/d). We view these dietary associations with colon cancer risk with caution. There were no other significant associations of dietary variables with colon cancer risk. Also, there were no significant associations between intake levels of DF, micronutrients, or food groups and rectal cancer risk.

From 1960 through 1973, the Hawaii Tumor Registry identified 781 Caucasian and 1073 Japanese cases of large bowel cancer. Survivorship analysis revealed that Japanese patients had a 32% higher 5-year relative survival rate than Caucasians. Further analyses showed that colon cancer cases did better than rectal cases, and patients diagnosed before 65 years of age fared better than cases diagnosed at an older age. As expected, patients with localized disease lived much longer than those who had more advanced disease. Men and women were similar in their survival from large bowel cancer. Histologic grade of the lesion, socioeconomic variables, behavioral practices and other factors which may affect survivorship by race could not be included in this study. Until such factors are also incoporated in the analyses, the observed results are only suggestive of a racial difference in survivorship.

1 Subcutaneous injections of clonidine (3.9 X 10(-8) mol/kg to 3.9 X 10(-6) mol/kg) produced forward locomotion and wall climbing in 7-day-old rats in a dose-dependent manner. 2 The effect was reduced significantly by a preceding intraperitoneal injection of phentolamine (7.9 X 10(-6) mol/kg), phenoxybenzamine (7.4 X 10(-6) mol/kg), yohimbine (1.3 X 10(-6) mol/kg) or piperoxan (7.4 X 10(-6) mol/kg). 3 The pA2-values of the antagonists to the clonidine-induced locomotor hyperactivity were: 5.1 (phenoxybenzamine), 5.2 (phentolamine), 6.4 (yohimbine) and 6.0 (piperoxan). 4 Metiamide (2.5 X 10(-4) mol/kg, 5.0 X 10(-4) mol/kg and 1.0 X 10(-3) mol/kg), a histamine H2-receptor blocker, did not affect the clonidine-induced locomotor stimulation. 5 It is suggested that the receptors which mediate clonidine-induced locomotor stimulation could be alpha-adrenoceptors but not histamine H2-receptors in the central nervous system of the infant rat.

From 1960 through 1974, the Hawaii Tumor Registry identified 1895 cases of lung cancer with either small cell or non-small cell carcinoma among the five main racial groups in the islands. There were 650 Caucasians, 549 Japanese, 362 Hawaiian, 173 Filipino and 161 Chinese patients. Analysis revealed that Caucasians with non-small cell carcinoma had a significantly poorer five-year survival rate than Chinese, Filipino, or Japanese patients after simultaneous adjustment for differences in sex, age at diagnosis, stage, and socioeconomic status. Men, older patients, patients with regional or distant disease, and patients in a middle or low socioeconomic status also did worse than the others. When the 170 patients with small cell carcinoma were compared with 1725 patients with non-small cell carcinoma, patients with small cell carcinoma had significantly poorer survival rates after five years.

This epidemiologic case-control study examined the relationship between replacement estrogen use and breast cancer risk in 2 population groups in Hawaii. No significant associations were observed when 161 Caucasian cases were compared with either their neighborhood controls (RR = 0.9; 95% Cl = 0.5-1.3) or their hospital controls (RR = 0.7; 95% Cl = 0.4 to 1.1) and when 183 Japanese cases were compared with either their neighborhood controls (RR = 1.1; 95% Cl = 0.7-1.6) or their hospital controls (RR = 1.0; 95% Cl = 0.6-1.4). The results indicate that the use of replacement estrogens cannot account for the large difference in breast cancer incidence between the 2 Hawaiian ethnic groups. However, further data analysis involving neighborhood controls was suggestive of a possible increase in breast cancer risk with estrogen use for certain sub-groups of women who are at high risk for the disease. These included estrogen users with a family history of breast cancer or a history of benign breast disease. These findings are in agreement with other studies which have used non-hospitalized controls. Because the numbers of cases in this study are not substantial, it is recommended that a large population-based case-control study be undertaken to clarify the relationship between breast cancer risk and replacement estrogen use, especially in sub-groups of women at high risk for the disease.

The authors compared the risk of dying from site-specific cancer within five years after diagnosis for Hawaii residents diagnosed in 1960-1964, 1965-1969, and 1970-1974. Twelve cancer sites were analyzed with adjustments for age at diagnosis and ethnicity by a multivariate method. Four of these sites were adjusted for sex as well. The adjusted relative risk for site-specific cancer death was significantly greater than 1.0 (P less than 0.05) when patients diagnosed in 1960-1969 were compared with those diagnosed in 1970-1974 for the following sites: stomach, rectum (males), lung, prostate, leukemia, and lymphoma. The adjusted relative risk was greater than 1.0, but not significantly greater, for the remaining cancer sites: colon, rectum (females), liver, pancreas, breast, corpus uteri, and ovary. These results indicate that, for several cancer sites, the risk of cancer death has significantly declined in Hawaii during 1960-1974. However, specific reasons for this improvement in cancer prognosis were not determinable from the available data.

The study reported here examines the survival experience up to 84 months of patients from the five major racial groups in Hawaii diagnosed with colorectal cancer during the years between 1960 and 1974 based on data in the Hawaii Tumor Registry. Previous research in Hawaii showed that racial differences in survival existed even after adjusting for sex, age at diagnosis, stage of the disease at diagnosis, and normal life expectancy. In this paper, socioeconomic status differences between racial groups are hypothesized as a possible explanation for these survival differences. The results show that socioeconomic status did account for some survival differences between racial groups beyond what could be explained by the other variables. After adjusting for all the covariates, the only statistically significant racial differences which remained were higher survival rates for the Japanese patients compared with the rates for the Hawaiian and Filipino patients. Socioeconomic status was not found, however, to have a statistically significant effect on survival independent of race or the other variables examined. Reasons for the modest effects of socioeconomic status in this study are discussed.