Kazuko Arakawa

Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire.

This report describes the development and validation/calibration of a structured food frequency questionnaire for use in a large-scale cohort study of diet and health in Chinese men and women aged 45-74 years in Singapore, the development of a food composition database for analysis of the dietary data, and the results of the dietary validation/calibration study. The present calibration study comparing estimated intakes from 24-hour recalls with those from the food frequency questionnaires revealed correlations of 0.24-0.79 for energy and nutrients among the Singapore Chinese, which are comparable to the correlation coefficients reported in calibration studies of other populations. We also report on the nutritional profiles of Singapore Chinese on the basis of results of 1,880 24-hour dietary recalls conducted on 1,022 (425 men and 597 women) cohort subjects. Comparisons with age-adjusted corresponding values for US whites and blacks show distinct differences in dietary intakes between the Singapore and US populations. The Singapore cohort will be followed prospectively to identify dietary associations with cancer risk and other health outcomes.

DNA methylation as a biomarker for cardiovascular disease risk.

Background Elevated serum homocysteine is associated with an increased risk of cardiovascular disease (CVD). This may reflect a reduced systemic remethylation capacity, which would be expected to cause decreased genomic DNA methylation in peripheral blood leukocytes (PBL). Methodology/Principal Findings We examined the association between prevalence of CVD (myocardial infarction, stroke) and its predisposing conditions (hypertension, diabetes) and PBL global genomic DNA methylation as represented by ALU and Satellite 2 (AS) repetitive element DNA methylation in 286 participants of the Singapore Chinese Health Study, a population-based prospective investigation of 63,257 men and women aged 45–74 years recruited during 1993–1998. Men exhibited significantly higher global DNA methylation [geometric mean (95% confidence interval (CI)): 159 (143, 178)] than women [133 (121, 147)] (P = 0·01). Global DNA methylation was significantly elevated in men with a history of CVD or its predisposing conditions at baseline (P = 0·03) but not in women (P = 0·53). Fifty-two subjects (22 men, 30 women) who were negative for these CVD/predisposing conditions at baseline acquired one or more of these conditions by the time of their follow-up I interviews, which took place on average about 5·8 years post-enrollment. Global DNA methylation levels of the 22 incident cases in men were intermediate (AS, 177) relative to the 56 male subjects who remained free of CVD/predisposing conditions at follow-up (lowest AS, 132) and the 51 male subjects with a diagnosis of CVD or predisposing conditions reported at baseline (highest AS 184) (P for trend = 0.0008) No such association was observed in women (P = 0.91). Baseline body mass index was positively associated with AS in both men and women (P = 0·007). Conclusions/Significance Our findings indicate that elevated, not decreased, PBL DNA methylation is positively associated with prevalence of CVD/predisposing conditions and obesity in Singapore Chinese.

HSD17B1 and CYP17 polymorphisms and breast cancer risk among Chinese women in Singapore

Reasons for the recent trend of increasing breast cancer incidence among Chinese and other Asian women are not well understood. Endogenous estrogen levels are strongly associated with breast cancer risk and its determinants include both genetic and lifestyle factors. We conducted a nested case‐control study to investigate, within the Singapore Chinese Health Study Cohort, the relationships between polymorphisms in 2 genes involved in estrogen metabolism, CYP17 and HSD17B1, and the risk of breast cancer. For this analysis, 188 incident breast cancer cases and 671 female cohort control subjects were compared. When the HSD17B1 A allele was considered as the “putative high‐risk” allele, there was a modest increased risk (adjusted relative risk, RR=1.37, 95% CI=0.90–2.07 for HSD17B1 AA vs. other); this association was statistically significant in analysis restricted to postmenopausal women (RR=1.86, 95% CI=1.14–3.03). There was no significant association between the CYP17 MspAI polymorphism and risk in all subjects (RR=1.06, 95% CI=0.65–1.74 for CYP17 A2A2 vs. CYP17 A1A1) or in postmenopausal women only. When we evaluated breast cancer risk in relation to the joint stratification of CYP17 and HSD17B1 genotypes and according to the combined number of putative high‐risk alleles (range, 0–4), we observed an elevated joint effect of the CYP17 and HSD17B1 genes on risk. Women who possessed all 4 putative high‐risk alleles of both genes (CYP17 A2A2 and HSD17B1 AA) vs. less displayed a nearly 2‐fold increased risk (RR=1.83, 95% CI=0.97–3.44); this finding was statistically significant in postmenopausal women (RR=2.31, 95% CI=1.07–4.98). Risk of breast cancer was similar among women possessing the other genotypes (i.e., less than 4 putative high‐risk alleles in the joint CYP17/HSD17B1 genotypes). In addition, the significant increased risk of breast cancer associated with nulliparity or late age at first live birth (age 31 years or older) was largely limited to women with the high‐risk CYP17 A1A2/A2A2 or HSD17B1 AA genotypes (RR=2.41, 95% CI=1.56–3.72; RR=4.39, 95% CI=1.71–11.30, respectively). The latter gene‐parity effects were especially pronounced in postmenopausal women.

249serp53 mutation in the serum of black southern African patients with hepatocellular carcinoma

Background and Aims:  A specific mutation at codon 249 of the p53 tumor suppressor gene (guanine to thymine; arginine to serine [249serinep53]) is present in the cell‐free plasma of 30–47% of patients with hepatocellular carcinoma (HCC) in regions with uniformly high levels of dietary exposure to the fungal toxin, aflatoxin B1. No information is available from other regions. We therefore examined cell‐free serum from HCC patients in southern Africa, where aflatoxin B1 exposure ranges from very high to low levels.

Respiration during the First Six Months of Life in Normal Infants. III. Computer Identification of Breathing Pauses

Summary: The first objective of this study was to quantify computer-identified breathing pauses in excess of two sec duration in relation to sleep states. The second objective was to examine which respiratory variables at one wk and one month of age predicted total apnea at 2 and 3 months of age.Short apnea (2 to 5 sec) were abundant in recordings of normal infants during the first one-half year of life. Apnea between 6 and 9 sec should be considered normal, whereas apnea in excess of 9 sec occurred most frequently in the first wk of life and declined sharply thereafter. Recording duration substantially affected apnea counts. Apnea at later ages could not be reliably predicted from recordings during the first wk of life.Speculation: Short breathing pauses in QS during the age span under investigation are probably inversely related to breathing rate and caused by the same mechanism responsible for the decline in rate. The change in breathing pauses over age in AS can probably be accounted for by two sources of variance, first, the decline in rate and second, rate-independent developmental changes in control of ventilation during AS.

1413 PHYSIOLOGIC FOLLOW UP OF PRETERM INFANTS WITH APNEA

Otherwise healthy preterm infants may continue to exhibit prolonged apnea beyond the first week of life, a condition some consider leading to an increased risk for SIDS. To elucidate the significance of these apnea, we studied 17 AGA infants between 32-36 weeks post conceptual age. Eight of these (A) exhibited 2 or more central apnea ≥20 sec. during an 8 hour period after the first week of life.Polygraphic records were obtained between 6-10 pm at 40 weeks, 1 month and 3 months adjusted age, from which Quiet Sleep (QS) and Active Sleep (AS) were derived. Minute by minute values for heart rate (HR), respiratory rate (RR), transcutaneous O2 (PtcO2) and CO2 (PtcCO2) were determined during AS and QS with a computer. Representative results at 40 wks are presented as mean and (sd).Apneic preterms were not different from non-apneic infants (N) at this either of the other follow up ages. While preterm infants are statistically at increased risk for SIDS, these data do not warrant singling out the apneic prcterm as at greater risk for abnormal autonomic sequelae.

ARE SLEEP STATES INFLUENCED BY APNEA AND PREMATURITY

Sleep and waking were studied in normal term and normal and apneic premature infants at 44 wks post-conceptual age. Percentages of active sleep (AS), quiet sleep (QS) and wakefulness (AW) were determined from polygraphic tracings obtained between 6-10 p.m. Term infants were selected by absence of disease and gestational age between 38-42 wks. Normal prematures were selected by absence of disease between 32 and 36 wks post-conceptual age. Apneic prematures were similar, except they had 2 or more apneic episodes ≥ 20 sec. within an 8 hour period after the first week of life for which no etiology could be found.In normal prematures total sleep time was decreased at the expense of AS, and wakefulness was increased. Apneic prematures were not different from normal term infants. Since QS was similar in all groups, maturation of the forebrain does not appear to be delayed. The data suggest a lower threshold for arousal in the normal premature. Stress produced by apnea in the premature infant appeared to accelerate development toward normal term patterns rather than to cause a delay.