Kiyoko Yagyu

Structural changes of immunoglobulin G oligosaccharides with age in healthy human serum

Age-related changes of IgG N-linked oligosaccharides isolated from normal human serum are reported for 403 individuals (male 227 and female 176), varying in age from 0 to 85 years. The IgG N-linked oligosaccharides were released from the protein by digestion with a glycoamidase and reductively aminated with the fluorescent reagent, 2-aminopyridine. The mixture of pyridylaminated oligosaccharides was separated at high resolution by HPLC using a reverse-phase column. From the results of neutral oligosaccharide analysis, agalactosyl glycoform and bisecting GlcNAc-containing glycoform were shown to increase with increasing age. Spearmans correlation coefficients were 0.503 and 0.473, respectively. Thus, in healthy people, an increase of both types of glycoforms correlates weakly with age. In addition, differences were demonstrated between male and female groups in their twenties. The quantity of agalactosyl glycoform was found to be lower in females than in males. No significant differences, however, were observed in the quantity of bisecting GlcNAc-containing glycoforms between males and females. Abbreviations: Gal, D-galactose: GlcNAc, N-acetyl-D-glucosamine; Man, D-mannose; Fc, C-terminal half of the heavy chain dimers of IgG; HPLC, high-performance liquid chromatography; IgG, immunoglobulin G; ODS, octadecylsilyl; PA, pyridylamino

Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, and the risk of pancreatic cancer death

Recent epidemiological studies have shown that high serum levels of insulin‐like growth factor‐I (IGF‐I) are associated with an increased risk of lung, colon, breast and prostate cancer. Since very few studies have addressed the role of serum levels of IGF‐I in the development of pancreatic cancer, we conducted a nested case‐control study to examine this association. The analysis involved 69 case subjects who died from pancreatic cancer during the follow‐up period of the study, and 207 control subjects matched for sex, age(±1 year) and study area, selected randomly from a cohort of 10,364 individuals. Serum levels of IGF‐I and IGF binding protein‐3 (IGFBP‐3) were measured by immunoradiometric assay, using commercially available kits. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic models. The levels of IGF‐I were positively correlated with IGFBP‐3 (r=0.55). There was a positive, but statistically insignificant association between serum levels of IGF‐I and risk of death from pancreatic cancer, with subjects in the highest quartile having an OR of 2.31 (95% CI=0.70–2.64) compared to those in the lowest quartile. The risk of pancreatic cancer death increased significantly with increasing serum levels of IGFBP‐3 (trend p=0.03). Further adjustment for IGFBP‐3 or IGF‐I slightly attenuated the positive associations. This nested case‐control study showed that high serum levels of IGF‐I and IGFBP‐3 may be associated with an increased risk of death from pancreatic cancer.

Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort.

It is unclear whether body mass index (BMI) and physical activity are associated with the risk of pancreatic cancer in Asian populations. We examined these associations in the Japanese Collaborative Cohort Study for Evaluation of Cancer Risk. Our cohort study included 110,792 Japanese men and women at enrollment (1988–1990). Data on height, body weight (at baseline and at age 20 years) and physical activity were obtained from a questionnaire. Cox proportional hazards models were used to estimate the relative risks of pancreatic cancer mortality. We observed a total of 402 pancreatic cancer deaths during the follow‐up period. Men with a BMI of 30 or more at age 20 years had a 3.5‐fold greater risk compared with men with a normal BMI. Women with a BMI of 27.5–29.9 at baseline had ∼60% increased risk compared with women with a BMI of 20.0–22.4. In men, weight loss of 5 kg or more between 20 years of age and baseline age was associated with an increased risk of pancreatic cancer death. In contrast, women with weight loss of 5 kg or more over the same period had a decreased risk. Physical activity was not associated with pancreatic cancer risk in either men or women. Obesity in young adulthood may be associated with an increased risk of death from pancreatic cancer in Japanese men. The risk of pancreatic cancer in relation to BMI seems to differ according to sex and the period over which BMI was measured.

BMI and all-cause mortality among Japanese older adults: findings from the Japan collaborative cohort study.

The association between BMI and all‐cause mortality may vary with gender, age, and ethnic groups. However, few prospective cohort studies have reported the relationship in older Asian populations. We evaluated the association between BMI and all‐cause mortality in a cohort comprised 26,747 Japanese subjects aged 65–79 years at baseline (1988–1990). The study participants were followed for an average of 11.2 years. Proportional‐hazards regression models were used to estimate mortality hazard ratios (HRs) and 95% confidence intervals. Until 2003, 9,256 deaths occurred. The underweight group was associated with a statistically higher risk of all‐cause mortality compared with the mid‐normal‐range group (BMI: 20.0–22.9); resulting in a 1.78‐fold (95% confidence interval: 1.45–2.20) and 2.55‐fold (2.13–3.05) increase in mortality risk among severest thin men and women (BMI: <16.0), respectively. Even within the normal‐range group, the lower normal‐range group (BMI: 18.5–19.9) showed a statistically elevated risk. In contrast, being neither overweight (BMI: 25.0–29.9) nor obese (BMI: ≥30.0) elevated the risk among men; however among women, HR was slightly elevated in the obese group but not in the overweight group compared with the mid‐normal‐range group. Among Japanese older adults, a low BMI was associated with increased risk of all‐cause mortality, even among those with a lower normal BMI range. The wide range of BMI between 20.0 and 29.9 in both older men and women showed the lowest all‐cause mortality risk.

Serum midkine concentrations and gastric cancer

Midkine (MK) is one of a family of heparin‐binding growth factors, and increased MK expression is reported in various types of human carcinomas. To clarify the association between serum MK (S‐MK) concentrations and gastric cancer, we examined S‐MK concentrations of gastric cancer patients (n = 275) and healthy controls (n = 275). S‐MK concentrations of all subjects were measured by enzyme‐linked immunosorbent assay (elisa). The medians (25th and 75th percentiles) of S‐MK were 192 (123 and 314) pg/mL in the cases and 170 (81 and 273) pg/mL in the controls (P < 0.01). We also compared S‐MK concentrations in each group divided by the progression stage or histological type of cancer. A difference was observed in the median S‐MK concentrations between early and advanced cancers [182 (105 and 301) pg/mL vs 203 (139 and 331) pg/mL, P = 0.07], but not between intestinal and diffuse type cancers [185 (121 and 306) pg/mL vs 198 (127 and 323) pg/mL, P = 0.51]. We found that those progression stages affect S‐MK concentration more strongly than the histological types in gastric cancer patients. Because S‐MK seems to reflect the progression stage of gastric cancer, it may serve as a useful marker in the clinical follow‐up of gastric cancer patients. (Cancer Sci 2005; 96: 54 –57)

Healthy lifestyle and preventable death: Findings from the Japan Collaborative Cohort (JACC) Study

OBJECTIVE To evaluate the effect of baseline combination of 6 lifestyle factors on all-cause mortality. METHODS A total of 62,106 Japanese men and women aged 40-79 years were followed for 12.5 years on average. Hazard ratios and 95% confidence intervals (CIs) of all-cause mortality in relation to healthy lifestyle factors (not currently smoking, not heavily drinking, walking 1 h or more per day, sleeping 6.5 to 7.4 h per day, eating green-leafy vegetables almost daily and BMI between 18.5 and 24.9) were calculated from proportional-hazards regression models. We also estimated population-attributable fractions of death to address the impact of potential lifestyle modifications on mortality. RESULTS Until 2003, 8497 deaths were observed. Age-adjusted HR of all-cause mortality for the group with 6 healthy lifestyle factors was 0.42 (95% CI: 0.32-0.56) among men and 0.49 (0.39-0.60) among women, respectively, compared with the group with 0-2 healthy lifestyle factors. Even at ages 60-79 years, a healthy lifestyle has a major impact on mortality. Had the subjects achieved even a 1-point increment in their lifestyle scores, death rates of 24.7% among men and 18.5% among women could have been reduced. CONCLUSION We found an inverse association between baseline combination of 6 healthy lifestyle factors and all-cause mortality as well as its impact on preventable fraction of death. Our results also demonstrated that healthy lifestyle behaviors are important even in old age.

Green tea consumption and the risk of pancreatic cancer in Japanese adults.

Objective: Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort. Methods: At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models. Results: During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women. Conclusions: Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.

Dietary Habits and Pancreatic Cancer Risk in a Cohort of Middle-Aged and Elderly Japanese

Abstract: Few epidemiological studies have examined associations between diet and pancreatic cancer in Japan. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we evaluated the relationship between dietary factors, including meat, vegetable, and fruit intake, and the risk of pancreatic cancer deaths. Among the original cohort established between 1988 and 1990, 46,465 men and 64,327 women aged 40–79 yr were followed-up through December 31,1999. During 1,042,608 person-years of follow-up, we documented 300 deaths from pancreatic cancer. A 33-item food-frequency questionnaire was used to assess dietary intake at the baseline survey. Cox proportional-hazards models were used to estimate the relative risks of pancreatic cancer death in relation to the intake frequency of food items. We did not observe an overall association between meat intake and pancreatic cancer risk. Except for a 50% decrease in risk associated with high fruit intake among men, we did not find other significant inverse relationships between vegetable and fruit intake and pancreatic cancer risk. Smoking did not modify the associations with dietary habits. Our study suggested that high consumption of pickles and wild edible plants, mainly bracken, might be related to increased pancreatic cancer risk; however, this finding should be confirmed in other epidemiological studies.

Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy

BackgroundAlthough age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase.MethodsWe have observed trends in the incidence of gastric cancer by sex and 20-year age groups over the past two decades (1976–1996). Source data were obtained from the cancer statistics materials provided by the Research Group for Population-Based Cancer Registration in Japan. Simultaneously, we observed changes in the prevalence of Helicobacter pylori infection and in serological atrophy of the gastric mucosa, and compared the results with those involving changes in the incidence of gastric cancer.ResultsA slight decline was observed in all age groups over 40 years old, in both men and women, between 1986 and 1996. However, a marked decline in incidence was observed for those aged 20–39 years. The prevalence of H. pylori infection declined in both sexes between 1989 and 1998. The frequency of serological atrophy of the gastric mucosa significantly declined in all age groups between 1989 and 1996, with young age groups experiencing a more marked decrease.ConclusionThe marked decline in gastric cancer incidence observed in the young population will also begin to occur in the elderly population in the future.

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: A prospective cohort study in Japan

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self‐administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40–89 years at entry were followed for 15 years. During the follow‐up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91–4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05–4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801–1,000 cigarette‐years were 3.18 [1.18–8.53] and 3.44 [1.40–8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or “cigarette‐years” (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29–9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.