Michiko Kurosawa

Relationship between Helicobacter pylori infection and smoking and drinking habits

Background : Helicobacter pylori is a major cause of various gastroduodenal diseases. Some risk factors related to H. pylori infection have been reported; however, studies on the relationship between H. pylori infection and smoking or drinking habits have given conflicting results. In the present study, these relationships were investigated by collecting sera and information from 8837 subjects.

Risk of pancreatic cancer in relation to alcohol drinking, coffee consumption and medical history: Findings from the Japan collaborative cohort study for evaluation of cancer risk

We evaluated the associations of such lifestyle factors as alcohol drinking, coffee consumption and medical history with risk of death from pancreatic cancer in a large‐scale prospective cohort study [the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC study)] in Japan. Subjects were 110,792 (46,465 men and 64,327 women) inhabitants who were enrolled from 45 areas throughout Japan. At baseline, a self‐administered questionnaire was used to obtain information on lifestyle factors and medical history. Cox proportional hazard models were used to calculate relative risks. During the follow‐up period (mean ± SD 8.1 ± 1.8 years), 225 deaths due to pancreatic cancer were identified. Overall, neither alcohol nor coffee intake was associated with risk of death from pancreatic cancer. Heavy coffee consumption (≥4 cups/day), however, may increase the risk. Men who reported a history of diabetes mellitus and women who reported a history of gallstone/cholecystitis were at significantly (2‐fold) increased risk of death from pancreatic cancer.

A prospective cohort study of cigarette smoking and pancreatic cancer in Japan

Objective: To examine the association of cigarette smoking with the risk of death from pancreatic cancer in a prospective cohort study. Methods: A total of 110,792 inhabitants, aged 40–79 years (46,465 men and 64,327 women), were enrolled from 1988 to 1990 and followed up for mortality to the end of 1997. At baseline a self-administered questionnaire was used to obtain information on cigarette smoking and other lifestyle factors. Results: During the follow-up period (mean ± SD: 8.1 ± 1.8 years), 225 deaths due to pancreatic cancer were identified. After adjustment for age, body mass index, history of diabetes mellitus, and gallbladder diseases, the relative risks (RRs) for current smokers were 1.6 (95% CI 0.95–2.6) in males, and 1.7 (95% CI: 0.84–3.3) in females. Men who smoked more than 40 cigarettes per day had a substantially higher risk of pancreatic cancer, with a RR of 3.3 (95% CI: 1.4–8.1). A significantly decreasing trend in risk with increasing years after smoking cessation was observed (trend p = 0.04) among male ex-smokers. The RRs were 0.85 (95% CI 0.36–2.0) and 0.85 (0.36–2.0) for those who had quit smoking for 10–19 and ≥20 years, respectively. Conclusions: Our cohort study confirmed that cigarette smoking was associated with an increased risk of death from pancreatic cancer.

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.

Association between infections with CagA-positive or -negative strains of Helicobacter pylori and risk for gastric cancer in young adults. Research Group on Prevention of Gastric Carcinoma Among Young Adults.

OBJECTIVE:We assessed the association between infection with CagA-positive and -negative Helicobacter pylori and the risk of gastric cancer in young adults.METHODS:CagA IgG antibodies were measured in sera of subjects participating in a case-control study in Japan. The study subjects were 103 gastric cancer patients <40 yr of age, 100 inpatients with benign diseases, and 101 screenees younger than age 43 yr.RESULTS:Compared with the H. pylori-negative/CagA-negative (H. pylori-/CagA−) group, both the H. pylori-positive/CagA-negative (H. pylori+/CagA−) group and the H. pylori-positive/CagA-positive (H. pylori+/CagA+) groups showed elevated odds ratios for intestinal-type, diffuse-type, early, advanced, proximal, and distal gastric cancers. All the relationships were significant except for the H. pylori+/CagA− group in relation to proximal cancer. The overall odds ratios (95% confidence intervals) for gastric cancer in the H. pylori+/CagA− and the H. pylori+/CagA+ groups were 15.0 (6.4, 35.2) and 14.6 (6.7, 31.9), respectively. Between these two groups, no significant difference was observed in risks for intestinal-type, diffuse-type, early, advanced, proximal, or distal gastric cancer.CONCLUSIONS:In those <40 yr of age, it is concluded that both CagA-positive and CagA-negative H. pylori infections are related to risks of intestinal-type, diffuse-type, early, advanced, and distal gastric cancers.

Association between infections with CagA-positive or -negative strains of Helicobacter pylori and risk for gastric cancer in young adults

Abstract OBJECTIVE: We assessed the association between infection with CagA-positive and -negative Helicobacter pylori and the risk of gastric cancer in young adults. METHODS: CagA IgG antibodies were measured in sera of subjects participating in a case-control study in Japan. The study subjects were 103 gastric cancer patients RESULTS: Compared with the H. pylori-negative/CagA-negative (H. pylori-/CagA−) group, both the H. pylori-positive/CagA-negative (H. pylori+/CagA−) group and the H. pylori-positive/CagA-positive (H. pylori+/CagA+) groups showed elevated odds ratios for intestinal-type, diffuse-type, early, advanced, proximal, and distal gastric cancers. All the relationships were significant except for the H. pylori+/CagA− group in relation to proximal cancer. The overall odds ratios (95% confidence intervals) for gastric cancer in the H. pylori+/CagA− and the H. pylori+/CagA+ groups were 15.0 (6.4, 35.2) and 14.6 (6.7, 31.9), respectively. Between these two groups, no significant difference was observed in risks for intestinal-type, diffuse-type, early, advanced, proximal, or distal gastric cancer. CONCLUSIONS: In those

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.

Effect of Age on the Relationship between Gastric Cancer and Helicobacter pylori

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10‐year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20–29, 14.5 for those aged 30–39, 9.1 for those aged 40–49, 3.5 for those aged 50–59, and 1.5 for those aged 60–69 (trend in odds ratios: P < 0.01). However, there was no such age‐dependent trend for early diffuse‐type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P=0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age‐class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age‐dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age‐independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and/or irreversible damage to gastric mucosa in childhood or the teenage years.