Associations between a PTPN11 polymorphism and gastric atrophy--opposite in Uzbekistan to that in Japan.

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A single nucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated with a lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy among the subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were 95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42 males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with serum pepsinogens (PG1<70 ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linked to the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association.

Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer.

OBJECTIVES: To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer. METHODS: We conducted a case-control study with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by the PCR-RFLP method. RESULTS: (1) When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer (age-, residence-, smoking-, alcohol drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64, 95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer (adjusted OR=0.47, 95%CI: 0.22-1.03). CONCLUSIONS: These results in the present study suggested that polymorphisms of the MTHFR C677T could influence susceptibility to colon or rectal cancer and that there was a coordinated effect between MTHFR A1298C A/A and C677T T/T genotypes among males.

The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer.

The Japan Multi-institutional Collaborative Cohort Study (J-MICC Study) launched in 2005, supported by a research grant for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science and Technology. Although the main purpose is to confirm and detect gene-environment interactions of lifestyle-related diseases, mainly of cancer, through the cohort analyses, it includes cross-sectional analyses on lifestyle factors, biomarkers, and genotypes, as well as confirmation/ screening of new biomarkers usable for early diagnosis of cancer. The endpoints are cancer diagnosis and death. The participants diagnosed as cancer will be identified through population-based cancer registries, hospital cancer registries, mail questionnaires, questionnaires at repeated visits, death certificates, health insurance data, and second survey questionnaires. Subjects are individuals aged 35 to 69 years enrolled from respondents to study announcements in specified areas, inhabitants attending health checkup examinations by local governments, visitors at health checkup centers, and patients at a cancer hospital. The number of subjects was set to be 100,000 throughout Japan. The enrollment period is from April 2005 to March 2010. The second survey is scheduled 5 years after their enrollment. The participants will be followed until 2025. The J-MICC Central Office is placed at Nagoya University Graduate School of Medicine. Ten participating research groups (Cohort Study Executing Groups) send baseline data and blood samples (buffy coat, serum, and plasma) anonymized with an identification number (J-MICC ID) to the Central Office. The data of second survey and follow-up will be linked using J-MICC ID. This study is expected to produce many findings on lifestyle and genetic traits associated with lifestyle-related diseases including cancer among Japanese.

Associations between serum C-reactive protein (CRP) levels and polymorphisms of CRP, interleukin 1B, and tumor necrosis factor genes among Japanese health checkup examinees.

C-reactive protein (CRP) is a sensitive marker of acute inflammation, which is associated with risk of cardiovascular and other chronic diseases. Some CRP polymorphisms are reported to affect the basal and stimulated CRP levels. Thus we conducted a population-based cross-sectional study to examine the associations of CRP levels with CRP C1444T polymorphism and two cytokine polymorphisms (IL-1B C-31T and TNF-A T-1031C), according to sex, age, smoking, alcohol, and BMI, in a total of 489 Japanese health checkup examinees (156 males and 333 females). Serum CRP levels were measured by high sensitivity latex-enhanced nephelometry. CRP C1444T, IL-1B C-31T and TNF-A T-1031C genotypes were genotyped by PCR-CTPP (polymerase chain reaction with confronting two-pair primers). Males, aged, smokers, and those with high BMI had a higher CRP on average. All genotype frequencies among the 489 subjects were in Hardy-Weinberg equilibrium. No significant associations of serum CRP levels with the genotypes of CRP C1444T and IL-1B C-31T were observed. TNF-A -1031CC polymorphism was significantly associated with high CRP values. For the females, those aged 61-69 years, never smokers, non-drinkers, or those with body mass index 24 or less, the association was remarkable. Since the biological mechanism is not clear, further investigations are required to confirm the association.

A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants.

OBJECTIVE: Observational epidemiologic studies have shown that a high intake of dietary and high serum levels of carotenoids are associated with a reduced risk of mortality from cancer and cardiovascular disease. To investigate whether high serum levels of carotenoids can reduce mortality rates, a population-based follow-up study was conducted among Japanese inhabitants. MATERIALS AND METHODS: Three thousand two hundred and fifty-four subjects (1,260 males and 1,994 females) aged from 39 to 85 years who had attended health check-up programs from 1989 to 1995 were recruited from the Japanese population. Serum levels of carotenoids, retinol and tocopherols were separately determined by high-performance liquid chromatography. Hazard ratios for serum values of carotenoids, retinol and tocopherols were estimated by Cox's proportional hazard model after adjusting for sex, age, and other confounding factors. RESULTS: During the 11.7-year follow-up period, 140 deaths (86 males and 54 females) from cancer of all sites were identified among the cohort subjects, including 41 from lung , 17 from stomach , 16 from colorectal and 12 from liver cancer, as well as 89 deaths from cardiovascular disease, including 45 from heart disease and 37 from stroke. High serum values of carotenoids including xanthophylls were apparently associated with low hazard ratios for mortality rates of cancer of all sites or of cardiovascular disease. High serum values of beta-carotene, total carotene, provitamin A and total carotenoid for colorectal cancer or stroke also appeared to be related to low hazard ratios. Those of retinol and tocopherols were not associated with any reduction in risk of mortality from cancer or cardiovascular disease. CONCLUSIONS: Our follow-up study demonstrated that a typical Japanese diet related to elevating serum levels of carotenoids with provitamin A activity may significantly reduce risk of mortality from cancer of certain sites or cardiovascular disease, especially colorectal cancer or stroke, while high serum levels of some xanthophylls, retinol and tocopherols do not.

No association of an SDHC gene polymorphism with gastric cancer.

It is widely reported that reactive oxygen species (ROS) cause apotosis and carcinogenesis. Marked infiltration of activated leukocyte and enhanced production of ROS appear to occur in the gastric mucosa infected with Helicobacter pylori (H. pylori). The previous studies reported that the mutation of the succinate dehydrogenase subunit C (SDHC) gene caused the increase in superoxide anion (O(2)(-)) and oxidative stress. To extend these findings, we epidemiologically investigated the association of a SDHC polymorphism at 3'-untranslated region of exon 6 (JST173800) with H. pylori infection, gastric atrophy and gastric cancer risk in Japan. The subjects consisted of 454 health checkup examinees without a history of cancer and 202 gastric cancer patients. The SDHC polymorphism was not associated with H. pylori infection seropositivity, gastric atrophy, and cancer risk in this study. Although the polymorphism at the 3'-untranslated region could be hypothesized to be functional, this study did not demonstrate any significant association of the SDHC gene polymorphism with gastric atrophy and cancer.

A pilot study on inducement of smoking cessation by a simple 5A (asking, advice, assess, assist, and arrange) approach at outpatient clinics.

Asking smokers about their smoking status, followed by advice to quit smoking, assessing the intention to quit, assistance with cessation, and arrange of follow-up (5A) is recommended for induction of smoking cessation. To obtain preliminary data on effects of "5A" , we investigated the smoking cessation rate with two modes in the phase I: 1) self-administered questionnaire and 2) doctor's interview at respiratory disease clinics of three general hospitals in Japan, and another mode in phase II: 3) doctor's interview with an additional pamphlet at one of the three hospitals. The interviews for smokers were conducted by doctors in charge of treatment. Subject smoking habits were followed up by postal surveys three months after the enrollment. In phase I, 359 outpatients were recruited and 189 smokers responded, among whom 27 patients (7.5% of 359 outpatients) had quit smoking at the three months after the enrollment. The cessation rate of the self-administered questionnaire group (8.4% of 238 smokers) did not differ significantly from that of doctors' interview group (5.8% of 121 smokers). Age and intention to quit at enrollment were found to be independent predictors of smoking cessation. Patients aged 50 years or older (odds ratio=5.05, 95% confidence interval 1.89-13.54), and participants with an intention to quit (odds ratio=6.78, 95% confidence interval 2.66-17.30) were more likely to be successful in quitting. In phase II, another 212 smokers of one hospital were interviewed by doctors in charge and provided with an additional pamphlet describing how to practice to dislike smoking. No significant difference in the cessation rate was observed between phase I and phase II (5.8% vs. 8.0%). In conclusion, there were no differences among the three modes of "5A", but 7.7% of the 571 outpatients visiting respiratory divisions quit smoking with this simple "5A". The findings may indicate that this simple practice at clinics is useful for smoking cessation strategy, although randomized trials are now required.

The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis.

Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.

Multiplex PCR with confronting two-pair primers for CYP1A1 Ile462Val, GSTM1, GSTT1, and NQO1 C609T.

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an effective genotyping method for single nucleotide polymorphisms (SNPs) in aspects of reducing time and costs for analysis. So far we have established PCR-CTPP conditions for tens of SNPs, including a triplex genotyping (Kawase et al., 2003). In the present study we report a quadruplex PCR-CTPP to genotype simultaneously four functional polymorphisms of carcinogen-metabolizing enzymes, CYP1A1 Ile462Val, GSTM1 null, GSTT1 null and NQO1 C609T, which were reported that they have significant associations with smoking-related cancers. We applied this method for 475 health check-up examinees to demonstrate the performance. Among the subjects, the genotype frequency of CYP1A1 Ile462Val was 56.8% for Ile/Ile, 38.1% for Ile/Val and 5.1% for Val/Val. The null type frequencies of GSTM1 and GSTT1 were 52.8% and 49.9%, respectively. And the genotype frequency of NQO1 C609T was 41.9% for C/C, 41.3% for C/T and 16.8% for T/T. Their distributions were similar to those reported for Japanese by other studies. To the best of our awareness, this is the first paper that reports the success in quadruplex PCR-CTPP. The applied polymorphisms are useful ones, which would be adopted not only for research purposes, but also for risk assessment of individuals exposed to carcinogenic substances. This convenient genotyping would be applied for cancer prevention especially in Asian Pacific regions, where expensive genotyping methods are hardly available.

GSTT1 and GSTM1 deletions, NQO1 C609T polymorphism and risk of chronic myelogenous leukemia in Japanese.

We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53-1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), 1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power are now required to confirm our findings.

Minimal sizes of cases with a susceptible genotype and minimal odds ratios among susceptible individuals in case-control studies.

OBJECTIVE: Disease risk elevation due to an environmental factor only for individuals with a susceptible genotype is a typical example of gene-environment interaction. In order to identify risk factors interacting with susceptible genotypes in case-control studies, presumptions on minimal size of cases with the susceptible genotype (S (min)) and odds ratio (OR) among the susceptible individuals (OR(susceptible)) are useful. MODEL: Proportion of exposed cases (P(1)) and OR for whole cases (OR(whole)) statistically detectable in a case-control study can be calculated in a conventional method. P(1) was assumed to be a weighted sum of the exposed among cases with the genotype (P(x)) and cases without the genotype (equal to proportion of the exposed among controls, P(0)), i.e., S P(x) + (1 - S) P0, where S is the size (proportion) of cases with the genotype. For each calculated P(1), S became the minimum (S(min)) in case of P(x) = 1. OR(susceptible) was calculated by {P(x) (1 - P(0))} / {(1 - P(x)) P(0)}. RESULTS: S(min) and OR(susceptible) were listed for the combinations of the above components. For example, a detectable P(1) was 0.638 for P(0)=0.5 in a case-control study with 200 cases (N(1)) and 200 controls (N(0)), when a error of a two-sided test was 0.05 with an 80% of power. In case of P(1)=0.638, OR(whole) was 1.77, producing S(min) = 0.277 for infinite OR(susceptible). It indicates that an environmental factor cannot be detected in case that a high-risk genotype frequency is less than 0.277. INTERPRETATION: If the size of cases with a susceptible genotype is expected to be less than S(min), case-control studies are unlikely to detect a significant OR of the environmental factor.

Relation of the CD36 gene A52C polymorphism to the risk of colorectal cancer among Japanese, with reference to with the aldehyde dehydrogenase 2 gene Glu487Lys polymorphism and drinking habit.

High consumption of white meat (or saturated fatty acids) and alcohol has been demonstrated to have a tendency to increase the risk of colorectal cancer, according to the level of malondialdehyde-deoxyguanosine adducts derived from lipid per-oxidation in the colorectal mucosa. CD36 plays important roles as a long-chain fatty acid translocase and oxidized low-density lipoprotein (LDL) scavenger, while alcohol is metabolized by aldehyde dehydrogenase 2 (ALDH2) and decreases transiently metabolism of dietary fat and serum lipids. To examine associations between the risk of colorectal cancer and the CD36 gene A52C polymorphism according to the ALDH2 gene Glu487Lys polymorphism and drinking habit, a hospital-based case-control study was conducted with 128 colorectal cancer cases and 238 cancer-free controls. Odds ratios (ORs) for the C/C genotype relative to the A/A genotype were 1.70 [95% confidence interval (CI), 0.76-4.11] and 4.24 (95% CI, 1.42-22.66) for men and women, respectively, with the low-activity (Glu/Lys + Lys/Lys) ALDH2 genotype. The high-activity (Glu/Glu) genotype for men and women had no associations. On the other hand, the OR for the C/C genotype with high frequency of drinking habit relative to the A/A genotype with low frequency of drinking habit among men was 3.63 (95% CI, 1.29-13.15). The number of women with a high frequency drinking habit was too small for any corresponding analyses. Our findings suggest a significant interaction between alcohol consumption and the CD36 gene A52C polymorphism related to the metabolism of long-chain fatty acids and oxidized LDL in the etiology of colorectal cancer.

A pilot study on genotype announcement to induce smoking cessation by Japanese smokers.

BACKGROUND: Genotype announcements related to susceptibility to hazardous effects of smoking may be effective to induce smoking cessation. METHODS: Subjects were municipal government employees, 63 young smokers employed in the previous year and 59 smokers with more than 45 pack-years, who were invited to educational sessions against smoking held in December 2003 and February 2004, respectively. In the session, those who wished genetic susceptibility tests (GSTM1, GSTT1, and NQO1 C609T) were enrolled in the study. The smoking habit was ascertained three times: at the session, one month later, just before the genotype announcement, and at the follow-up three months after the announcement. RESULTS: Fifty eight (92.1%) and 49 (83.1%) smokers participated in the study, respectively. One out of 58 smokers was not a habitual smoker, so was not included in the analysis. The smoking cessation rates were 15.8% (9 participants) and 6.1% (3 participants) just before the genotype announcement, and 7.0% (4 participants) and 10.2% (5 participants) at the follow-up, respectively. All subjects were satisfied with the genotype testing except for two who rather regretted participating, but one of whom actually quit smoking. CONCLUSION: The present pilot study without controls indicated that the effects of genotype announcements in this framework on smoking cessation were less than might have been expected. The temporary effect of the session on younger smokers may have been due to the participation per se. The potential effects of genotype announcements for heavy smokers should now be examined in studies with adequate controls.

Helicobacter pylori eradication as a preventive tool against gastric cancer.

Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking.

Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.

Precise definition of anonymization in genetic polymorphism studies.

Anonymization is an essential tool to protect privacy of participants in epidemiological studies. This paper classifies types of anonymization in genetic polymorphism studies, providing precise definitions. They are: 1) unlinkable anonymization at enrollment without a participant list; 2) unlinkable anonymization before genotyping with a participant list; 3) linkable anonymization; 4) unlinkable anonymization for outsiders; and 5) linkable anonymization for outsiders. The classification in view of accessibility to a table including genotype data with directly identifiable data such as names is important; if such tables exist, staff may obtain genotype information about participants. The first three modes are defined here as anonymization unaccessible to genotype data with directly identifiable information for research staff. Anonymization with a key code held by participants is possible with any of the above anonymization modes, by which participants can access to their own genotypes through telephone or internet. A guideline issued on March 29, 2001 with collaboration of three Ministries in Japan defines "anonymization in a linkable fashion" and "anonymization in an unlinkable fashion", "for the purpose of preventing the personal information from being divulged externally in violation of law, the present guidelines or a research protocol", but the contents are not clear in practice. The proposed definitions will be useful when we describe and discuss the preferable mode of anonymization for a given polymorphism study.

No association of the mitochondrial genotype (Mt5178A/C) with six cancers in a Japanese population.

To examine an association between the mitochondrial DNA (mt5178) genotype and various cancers, we genotyped 1120 non-cancer controls and 930 cancer cases including esophageal, stomach, colorectal, lung, breast and malignant lymphoma in a sample of Japanese patients. The mt5178A/C was genotyped by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP). The frequency of mt5178A/C within the non-cancer and cancer groups, and age distribution of subjects with mt5178A and C were investigated. Odd ratios (ORs) of the mt5178A and C genotypes were also examined. The frequency of mt5178A was 39.1% in non-cancer subjects while frequencies in those having cancer included 39.0% in breast, 37.4% in colorectal, 45.1% in esophageal, 38.0% in lung, 41.5% in malignant lymphoma, and 38.8% in stomach cancer. There was no significant difference in the frequency of the mt5178 genotype among the six types of cancer studied. There was also no significant difference in the frequency of the mt5178 genotype between non-cancer and cancer subjects regardless of total age with the exception that ages 40-49 years (the frequency of the mt5178A was higher in cancer subjects). There was a significant interaction term between age and the mt5178 genotype in older (age>=60) lung cancer patients. The cumulative frequency of mt5178C increased more markedly than that of mt5178A after age 40 in non-cancer subjects, and after age 50 in cancer subjects ORs of the genotype were not significant for all cancers combined or for any individual site of cancer. In the present study, the mt5178 genotype seems to have no association with any of the cancers examined here. But an interaction term between the mt5178 genotype and aging on cancer was suggested with the Japanese population under study.

Reproducibility of a food frequency questionnaire in koreans.

Objective : The present study was conducted to report upon the reproducibility of a 98-item food frequency questionnaire among Koreans. Subjects : The study subjects were recruited from among those who visited for a regular health check-up at the health centers from Samsung Hospital and Hallym University Hospital. Setting : The FFQ was administered first in April to June of 2002 to 145 Korean adults aged 40 and over residing in Seoul and its vicinity and was then re-administered to 126 three months later between July and September of 2002 (FFQ 1 and FFQ 2). Methods : Reproducibility was evaluated using the Pearson correlation coefficients of log-e and the calorie-adjusted nutrient score. Weighted kappa (k) statistics with 95% confidence limits were calculated to assess the chance adjusted level of agreement between the FFQ 1 and the FFQ 2. The proportions of correctly categorized subjects in the same or adjacent quintiles were calculated. Results : The average intake in FFQ 1 was no more than 12 percent different from the average intake in FFQ 2. Correlations varied between 0.47 for sodium and 0.72 for vitamin C. All k values exceeded 0.5 except that of fiber. The average k for all nutrients was 0.67. The percentage agreement varied from 62% for energy and potassium to 82% for vitamin B(2) and cholesterol. The average of the agreement was 72%. Conclusion : The results of this study verify that it is possible to use tailored, relatively simple, but comprehensive, self-administered food frequency questionnaires to study nutrient consumption in large-scale epidemiological studies.

Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women.

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors (IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein-3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in breast cancer development and interaction of IGF systems.

Different risk relations with smoking for non-small-cell lung cancer: comparison of TP53 and TP73 genotypes.

BACKGROUND: The association between TP53/TP73 gene polymorphisms and tobacco smoking was evaluated with regard to risk of non-small cell lung cancer (NSCLC). METHODS: A case-control study with 192 histologically confirmed NSCLC cases and 241 non-cancer controls was conducted. Subjects were genotyped for TP53 Arg72Pro and TP73 G4C14 to A4T14 polymorphisms by PCR-based methods. Risk and interactions were assessed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The analyses according to TP53 genotypes for the risk of tobacco smoking illustrated that risk with heavy smoking was much higher for subjects with the TP53 ProPro genotype (OR: 16.4, 95% CI 1.77-151.7) as compared with those with TP53 ArgArg/ArgPro (3.36, 1.69-6.68). Similar analyses for TP73 genotypes did not show any differences for NSCLC risk. CONCLUSION: A risk relation of heavy smoking for the NSCLC is suggested with the TP53 but not the TP73 polymorphism.