Men Of Japanese Ancestry Research Articles

FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-aged Men: Kuakini Honolulu Heart Program.

This study tested whether carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension. Subjects were American men residing on Oahu having Japanese (n=5415) or Okinawan (n=897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years. During follow-up there were 1,629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (HR 1.61; 95% CI 1.44-1.80), P<0.0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p=0.11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p=0.038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p=0.021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p=0.054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p=0.61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p=0.79) heritage. The present prospective study found longevity associated FOXO3 genotype did not independently affect risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3 TT genotype may merit particular attention in CAD prevention programs.

The Impact of ApoE and FOXO3 Genotype on the Risk of Intracerebral Hemorrhage Among American Men of Japanese Ancestry

This study assessed the impact of APOE e2, e4 minor alleles and the FOXO3 longevity-associated genotype (carrier of SNP rs2802292 “G” allele) on 34-year incidence of intracerebral hemorrhage (ICH). Cox regression models were performed to assess the impact of the APOE e2, e4 and FOXO3 G alleles on the incidence of ICH. A total of 6483 participants were eligible for the analyses. 213 participants developed ICH. Cox-regression model showed neither APOE minor allele vs. common genotype (APOE e3/e3: RR 0.89, 95% CI: 0.64-1.22, p=0.46) nor FOXO3 G carrier status (RR 0.97, 95% CI: 0.72-1.29, p=0.82) was associated with incident ICH. Conversely, both hypertension (RR: 1.46, 95% CI: 1.07-2.00, p=0.02) and low cholesterol level (RR: 0.99, 95% CI: 0.99-1.00, p=0.001) were associated with incident ICH. Carriage of APOE e2 or E4 alleles and the FOXO3 G allele do not appear to impact risk of ICH over 34 years in this cohort.

Abstract P176: Genes That Increase Human Lifespan By Protecting Against Risk Of Death From Cardiometabolic Diseases

Further to our FOXO3 findings last year, we asked whether other longevity gene variants work by mitigating mortality risk from aging-related diseases. In a longitudinal study, 3,584 American men of Japanese ancestry from the Kuakini Honolulu Heart Program were followed from baseline (Exam 4, 1991-93) until Dec 31, 2019 (1% of men) or death (99%). At baseline, 2,512 subjects had either diabetes (n=1,010), hypertension (n=1,919) or coronary heart disease (CHD; n=738), and 1,072 lacked any cardiometabolic diseases (CMD). DNA samples for genotyping were obtained at baseline. Genotype frequencies of SNPs in MAP3K5 , PIK3R1 , GHR, CTGF , EGFR , FLT1 , SIRT5 and SIRT7 were compared between subjects with and without ageing-related diseases . In subjects with CMD, MAP3K5 rs2076260 longevity-associated genotypes CC and CC + TT were associated with longer lifespan (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12-1.35, p= 2.5x10 -5 ] in a major allele homozygote model, and 1.22 [95% CI: 1.11-1.33, p= 1.10x10 -5 ] in a heterozygote disadvantage model) compared with CT . For diabetes, hypertension and CHD, HR p -values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. For PIK3R1 , subjects with cardiovascular disease (CVD) having the longevity-associated genotypes TT / CC of SNP rs7709243 had survival curves similar to those of subjects without a CVD (HR 1.26 [95% CI, 1.14-1.39; p =0.0000043]). In contrast, survival curves of subjects with the CT genotype were significantly lower compared with survival curves of subjects without a CVD ( p =0.0000012 compared with TT / CC , and p =0.0000028 compared with CT ). For GHR SNP rs4130113 , in a heterozygote disadvantage model GG vs longevity-associated AG genotype was associated with reduced mortality risk from hypertension (HR 1.23 [95% CI, 0.94-1.41; p =0.0041]). Men without CVD showed no association of longevity-associated genotype with lifespan. For each gene, men without the disease outlived men with disease ( p &lt; 10 -6 ), but genotype had no effect on lifespan. In conclusion, for MAP3K5 , PIK3R1 and GHR , but not other longevity genes, longevity genotype increases lifespan only in individuals who have CMD, CVD or hypertension, likely by protection against disease-related cellular stress.

The FoxO3 Longevity Genotype Is Associated With Better Survival After Acute Myocardial Infarction in Older Patients

Background: Although numerous studies have been published on prognostic factors after a first acute myocardial infarction (AMI) among middle-aged men, little is known about the prognostic factors and genetic determinants for post-AMI elderly patients. Methods: The Kuakini Honolulu Heart Program (KHHP) is a prospective population-based study of cardiovascular disease (CVD) (defined as coronary heart disease (CHD) and stroke) among men of Japanese ancestry living in Hawaii. We identified 141 first AMI patients from participants of the KHHP exam 4 (1991-93) by ECG and/or cardiac enzymes (onset age: 73-96 years). Men who survived more than one year after AMI were followed for mortality from onset of AMI to December 2018 (all were deceased by 28 years of follow-up). All had FOXO3 genotype information available. Quantile regression was used to compare the median survival times of FOXO3-G allele carriers (longevity genotype) with FOXO3-TT homozygotes (common genotype). Results: Adjusting for age at AMI onset, baseline body mass index (BMI) and glucose levels (at exam 4), median survival times differed between FOXO3-G allele carriers and FOXO3-TT homozygotes by 2.1 years (95% CI=0.24-3.95, p=0.027). Adding other known CHD risk factors (i.e. hypertension, etc.) to the model reduced the difference to 2.03 years (95% CI=0.17-3.89, p=0.033). Furthermore, chi-square testing showed the mortality rate from CVD among FOXO3-G allele carriers was significantly lower than that among the common FOXO3-TT genotype. Conclusions: The data suggest that the FOXO3 longevity genotype reduces the risk of dying from CVD and extends survival time of elderly patients with acute myocardial infarction.

Abstract P113: Genotypic Effect Of Foxo3 On Lifespan Is Confined To Men With A Cardiometabolic Disorder (hypertension Or Coronary Heart Disease Or Diabetes)

FOXO3 is a prominent human longevity gene. To date, no-one has examined whether longevity-associated genetic variants of FOXO3 protect against mortality in all individuals, or whether they protect against mortality only in individuals with aging-related diseases. Here, we examined this issue for the first time. We tested 9 representative longevity associated single nucleotide polymorphisms (SNPs) located within a haplotype block of FOXO3 for association with mortality in 3,584 elderly American men of Japanese ancestry. At baseline (1991-1993), 2,512 had either diabetes (n=1,010), coronary heart disease (CHD; n=738), or hypertension (n=1,919), and 1,072 lacked any of these cardiometabolic disorders (CMDs). The men were followed from baseline until Dec 31, 2019. The longevity-associated (minor) alleles of all 9 SNPs were strongly associated with longer lifespan in individuals who had a CMD (covariate-adjusted hazard ratios [HRs] for each SNP: 0.82-0.95 [ P =0.00008 to 0.020]; covariate adjusted haplotype analysis HR=0.81, P =0.0003). For just diabetes, just hypertension, and just CHD, haplotype HRs were 0.77, 0.82 and 0.83 ( P =0.007, 0.0003 and 0.10), respectively. Reduced mortality was strongest for carriers of the minor ( G ) allele of SNP rs2802292 (covariate adjusted HR=0.82, 95% CI 0.75-0.90; P= 0.00008), as were survival curve differences (covariate adjusted Cox proportional hazard model difference, P =0.0002). As expected, men without a CMD outlived men with a CMD (Kaplan-Meier Log-rank chi-squared=24.8, P =0.0001). There was, however, no genotypic difference in lifespan of men who did not have a CMD (haplotype HR 1.02, P = 0.74). We propose that in individuals with a cardiometabolic disorder, longevity-associated genetic variants of FOXO3 enhance resilience mechanisms in cells and tissues to help protect against cardiometabolic stress caused by CMDs, thereby allowing CMD-affected men to live longer than men without the protective variants.

Society and health of migrants.

Society and health of migrants.

Abstract 662: Association Analysis of Raptor Gene Variants with Overweight and Hypertension in American Men of Japanese Ancestry

The mechanistic target of rapamycin (mTOR) pathway is pivotal for cell growth and has been implicated in aging, cardiovascular disease, obesity, diabetes and cancer. mTOR signaling is involved in cardiac leptin-mediated cardiac hypertrophy and fibrosis associated with obesity. mTOR is a key component of two multiprotein complexes, mTOR complex 1 and mTOR complex 2. The former is pro-growth and contains a unique protein, raptor. The present study tested for the first time whether genetic variation across the raptor gene ( RPTOR ) is associated with overweight/obesity, essential hypertension (EHT) and isolated systolic hypertension (ISH). We genotyped 61 common (allele frequency ≥ 0.1) tagging single nucleotide polymorphisms (SNPs) that captured most of the genetic variation across RPTOR in 374 subjects of normal lifespan and 439 subjects with a lifespan exceeding 95 years. Subjects were drawn from the Honolulu Heart Program, a homogeneous population of American men of Japanese ancestry, well characterized for phenotypes relevant to conditions of aging. Hypertension status was ascertained when subjects were 45–68 years old. Statistical evaluation was performed by contingency table analysis, logistic regression and recursive partitioning (RP), which is regarded as amongst the most powerful methods for statistical analysis of large complex sets of genetic information. After analysis of RPTOR genotypes by each statistical approach we found no significant association between genetic variation in RPTOR and either EHT or ISH. For EHT, RP revealed that even the most predictive SNPs ( rs4969322 and rs4890052 ) provided little contribution to correctly assigning individuals to EHT or NT ( P =0.22 by Z test). In the case of ISH, RP revealed that only one SNP ( rs2589118 ) made a noticeable contribution, and that this was no better than the contribution from the weakest laboratory/examination variable (overweight/obesity). In contrast, for overweight/obesity, the RP model revealed that RPTOR SNPs significantly enhanced the predictive capacity of the model ( P =0.008 by one-tailed Z test). In conclusion, genetic variation across RPTOR is associated with overweight/obesity, but not EHT or ISH in the populations of normal lifespan and of long-lived subjects studied.

Correction: Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry

Correction: Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry

Replication of Prostate Cancer Risk Loci in a Japanese Case–Control Association Study

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Low high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report.

A working group meeting was convened from January 7 to 8, 2000, in Naples, Florida, to assess low HDL cholesterol (HDL-C) concentration as a risk factor for coronary heart disease (CHD). The 30 speakers and discussants at this 2-day meeting included specialists in epidemiology, endocrinology, molecular biology, public health, lipid metabolism, cardiovascular medicine, and preventive cardiology from the United States, Europe, and Australia (Appendix). The group’s wide-ranging presentations and discussions considered the latest knowledge on HDL metabolism and the effects of interventions for raising HDL-C levels on the development of atherosclerosis. It was generally accepted that low HDL-C may be a marker for the metabolic syndrome, an enhanced atherosclerotic disease state that is also associated with an impaired response to insulin, hypertriglyceridemia, and abdominal obesity. Therefore, beyond risk assessment based on LDL cholesterol (LDL-C) alone, the case has been made for considering HDL-C in tandem with triglycerides (TG) as synergistic coronary risk factors.1 The following article summarizes the participants’ discussion of low HDL-C as an independent CHD risk factor and identifies areas requiring further research. Although population studies indicate that a high level of HDL-C in general protects against CHD,2 3 a high HDL-C concentration in any given individual may not necessarily confer cardioprotection. The atherogenicity of low HDL-C seems to be influenced by an array of genetic and environmental factors. Tangier disease, a disorder caused by mutations in the ATP-binding cassette transporter 1 ( ABC1 ) gene,4 is characterized by the absence of normal HDL, with only a very small quantity of abnormal HDL present. However, early atherosclerosis (before 40 years) is not a consistent feature of this disorder.5 In men of Japanese ancestry in Hawaii, mutations in the gene for plasma cholesteryl ester transfer protein ( CETP ), which transfers cholesteryl ester from HDL to TG-rich lipoproteins, have …

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.

Hepatitis B and C Virus Serologies among Japanese Americans with Hepatocellular Carcinoma

A cohort of 5924 Japanese American men was examined between 1967 and 1970 for hepatocellular carcinoma (HCC). By 1992, 24 incident cases of HCC were histologically confirmed in the group. Frozen serum samples from the 24 men with HCC and 72 age-matched controls were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen, antibodies to HBsAg, and antibodies to hepatitis C virus. HBsAg was detected in 15 (62.5%) of 24 HCC cases compared with 2 (2.8%) of 72 controls (odds ratio, 43.0; 95% confidence interval, 5.7-325.5). None of the cases and only 1 control had antibody to hepatitis C virus. This study demonstrates a strong association between hepatocellular carcinoma and hepatitis B virus infection, but not with hepatitis C virus infection, among men of Japanese ancestry in Hawaii.

Molecular patterns and sequence polymorphisms in the red and green visual pigment genes of Japanese men.

The red-green pigment gene arrays of 203 (101 from a previous study and 102 from this study) randomly selected men of Japanese ancestry from the Seattle area were screened for the abnormal molecular patterns (deletions and red/green or green/red hybrid genes) that are usually associated with defective color vision. Such molecular patterns were found in approximately 5% of these individuals, which is equivalent to the frequency of phenotypic color vision defects in Japanese males in Japan. Thus, the majority of hybrid genes carried by Japanese males appear to be associated with defective color vision. In contrast, the frequency of hybrid genes among Caucasians and African-Americans is approximately two and five times the frequency of color vision defects in these two ethnic groups, respectively. The coding sequences of 50 males of Japanese ancestry were determined. All the polymorphisms in the red and green pigment genes that were detected in the Japanese sample had been observed in Caucasians and African-Americans. The same polymorphisms of the red pigment gene were present in the green pigment gene, suggesting that gene conversion contributes to sequence homogenization between these pigment genes. As is the case for Caucasians, exon 3 of the red and green pigment genes was observed to be a hot spot for recombination and gene conversion. Fewer polymorphic sites (4 vs 11) and haplotypes (5 vs 14) of the red pigment gene were observed in Japanese than in Caucasians. The Japanese population was more uniform with respect to the red pigment gene, with 70% of individuals having the same haplotype, as compared with the 43% for the Caucasian population. This difference was largely due to the lower degree of polymorphism at position 180 of the red pigment gene in Japanese (84% Ser and 16% Ala vs 62% Ser and 38% Ala.) The number of polymorphic sites and haplotypes in the green pigment gene was similar in the two populations. Nevertheless, the Japanese population was more uniform with 65% having the same haplotype. The difference in the frequency of alleles at position 283 accounted for this difference in haplotype distribution.

Trends in stroke incidence and mortality in Hawaiian Japanese men.

Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence.Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11,136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988.Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorr...

Are aortic aneurysms caused by atherosclerosis?

The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.

Occupational strain and the incidence of coronary heart disease.

The hypothesis that men in high "strain" occupations have an increased risk of developing coronary heart disease was tested during an 18-year follow-up study from 1965-1983 of a cohort of 8,006 men of Japanese ancestry in Hawaii. There were no significant associations between the incidence of coronary heart disease and the individual job components of high psychologic demands and low job control or for the high strain interaction of these two characteristics. There were, in fact, trends of associations opposite to that predicted by the job strain model which were of borderline significance in multivariate analyses. Stratified analyses by level of acculturation showed similar inverse associations of job strain and coronary heart disease for the more Westernized men and no association for the more traditional men. There were also no significant associations among the various job characteristics and the major risk factors for coronary heart disease in this cohort. The disagreement of these results with those from other studies may be due to methodologic differences of using men whose usual and current occupations were the same in this study compared with using only current occupation in the other studies, the use of different methods of measuring job strain, or the possibility that men in this cohort perceive or react to occupational strain differently.

The Nineteen-Year Trends in CHD in the Honolulu Heart Program

Accumulated data from the Honolulu Heart Program cohort of men of Japanese ancestry were analysed for 19-year trends in coronary heart disease (CHD) mortality and incidence rates, case-fatality ratios, and changes in risk factor levels. From 1966 to 1984, there was an estimated average annual decline of 2.7% for CHD mortality rates for the population from which the cohort was drawn. This decline was similar to that of US white males of the same age distribution. Within the examined cohort of men who were free of prevalent CHD at entry into the study, the temporal pattern of incidence rates of definite CHD was quite similar to the pattern of CHD mortality rates. Thus, for the examined cohort, mortality rates were an accurate indication of incidence rates. There was no evidence that the decline in CHD mortality rates was due to reductions in case-fatality ratios. There were, however, significant decreases in the percentages of men who smoked cigarettes, in blood pressure level among treated hypertensives and in the intake of dietary cholesterol. These changes, and a drop in coronary artery atherosclerosis measured during the same time period, are all compatible with the concept that the decline of CHD mortality among Japanese men in Hawaii reflects primary prevention of new disease.

A prospective study of mortality and morbidity among carpenters in the Honolulu Heart Program Cohort.

The relationship of occupation as a carpenter to the development of definite coronary heart disease, stroke, cancer and total mortality was examined in men of Japanese ancestry participating in the Honolulu Heart Program. After 18 years of follow-up those men who indicated that their present and usual occupation was carpentry had a significantly lower age-adjusted rate of definite coronary heart disease and a significantly lower mortality rate compared to participants who were never occupied as carpenters. There were no significant differences for age-adjusted rates for stroke and cancer nor any differences for those whose usual occupation was carpentry but present occupation was not carpentry. These results were unchanged when controlling for several cardiovascular risk factors and potentially confounding variables. Unlike earlier observations, these findings are not affected by the "healthy worker bias" and support the relationship that carpentry is associated with lower rates of cardiovascular disease.

A Comparison of the 12-Year Mortality and Predictive Factors of Coronary Heart Disease Among Japanese Men in Japan and Hawaii

The mortality and predictive factors of coronary heart disease among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 years follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of coronary heart disease and aged 45-69 at baseline examination in 1965-1968, 20 (Japan) and 123 (Hawaii) cases of fatal coronary heart disease were identified. The age-adjusted mortality rate was 40% higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of coronary heart disease mortality. Although the associations of risk factors with coronary heart disease tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed to be definitive because of the small number of cases, especially in Japan.

Black tea consumption and cancer risk: a prospective study.

In a prospective cohort study, men of Japanese ancestry were clinically examined from 1965 to 1968. For 7,833 of these men, data on black tea consumption habits were recorded. Since 1965, newly diagnosed cancer incidence cases have been identified: 152 colon, 151 lung, 149 prostate, 136 stomach, 76 rectum, 57 bladder, 30 pancreas, 25 liver, 12 kidney and 163 at other (miscellaneous) sites. Compared to almost-never drinkers, men habitually drinking black tea more than once/day had an increased relative risk (RR) for rectal cancer (RR = 4.2). This positive association (P = 0.0007) could not be accounted for by age or alcohol intake. We also observed a weaker but significant negative association of black tea intake and prostate cancer incidence (P = 0.020). There were no significant associations between black tea consumption and cancer at any other site.