Biomedical subjects

Satoshi Sasaki

Publications and source records attributed to Satoshi Sasaki.

At least 109 records · Page 6Linked to original sources

PubMed2003

Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I to assess fatty acid intake: comparison with dietary records and serum phospholipid level.

We compared fatty acid intake estimated from our 138-item food frequency questionnaire (FFQ) with 28-day weighed dietary records among a subgroup of JPHC Study Cohort I (102 men and 113 women), and with the corresponding two serum phospholipid levels (88 men). Spearman rank correlation coefficients between fatty acid intakes estimated from FFQ and intakes estimated from DR were as follows: saturated fatty acid, r=0.61 and r=0.60; monounsaturated fatty acid, r=0.50 and r=0.44; for energy adjusted value and Eicosapentaenoic acid (EPA), r=0.62 and r=0.55; docosahexaenoic acid (DHA), r=0.61 and r=0.50; for percentage of total fatty acid intake in men and women, respectively. Spearman rank correlation coefficients between fatty acid intakes estimated from FFQ and the corresponding serum phospholipid levels (% of total fatty acid) were as follows: EPA, r=0.43 and r=0.59; DHA, r=0.35 and r=0.49; for crude value (g/day) and percentage of total fatty acid intake, respectively. In conclusion, relatively high correlations were observed for SFA, MUFA and marine-origin n-3 polyunsaturated fatty acid, whereas we must take into account the indicator of each fatty acid intake when using the data of fatty acid intake assessed with FFQ for JPHC study.

Diet Records↗

PubMed2003

Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I to assess carotenoids and vitamin C intake: comparison with dietary records and blood level.

We compared carotene and vitamin C intake assessed with our 138-item food frequency questionnaire (FFQ) against 28-day weighed dietary records among a subgroup of JPHC Study Cohort I (102 men and 113 women), and the corresponding serum carotenoid levels or plasma vitamin C levels (86 men and 100 women). Correlation coefficients between carotenoids or vitamin C intake estimated from FFQ and intakes estimated from DR were as follows in men and women, respectively: alpha-carotene, r=0.47 and r=0.46; beta-carotene, r=0.40 and r=0.30; lycopene, r=0.18 and r=0.22; vitamin C, r=0.44 and r=0.31. Correlation coefficients between carotenoids or vitamin C intake estimated from FFQ and the corresponding serum carotenoids levels or plasma vitamin C levels were as follows: alpha-carotene, r=0.38 and r=0.30; beta-carotene, r=0.28 and r=0.11; lycopene, r=0.30 and r=0.19; vitamin C, r=-0.07 and r=0.06; in men and women, respectively. These data indicated carotenoid and vitamin C intakes estimated from FFQ were associated with intake from DR, although the association was weak for lycopene. Carotenoid intake estimated from FFQ were associated with corresponding serum carotenoid levels in men, but the correlation was weak in women except for alpha-carotene. Both in men and women, no association was observed for plasma vitamin C levels.

Ascorbic Acid↗

PubMed2003

Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study to assess selenium intake: comparison with dietary records and blood levels.

Selenium (Se) levels in serum and erythrocytes were measured in 215 adults to assess the relative validity of Se intake estimated from 28-day dietary records (DR) and the food frequency questionnaire (FFQ) used in the 5-year follow-up survey of the JPHC study. Se intake estimated from DR was correlated with that from the FFQ both in males and females (r=0.36 and r=0.32, respectively). Se levels in erythrocytes were weakly correlated with Se intake by DR for men (r=0.21) after adjustments for the total energy intake, though no significant correlation was found for women nor in crude values for either sex. Although Se intake estimated from our FFQ was correlated with that from the DR, no correlation was observed between the Se level in serum and estimated Se intake. In this population, the serum Se level was not a good biomarker for estimated Se intake.

Analysis of Variance↗

PubMed2003

Validity of the self-administered food frequency questionnaire used in the 5-year follow-up survey for the JPHC Study to assess folate, vitamin B6 and B12 intake: comparison with dietary records and blood level.

To validate a self-administered food frequency questionnaire (FFQ) for the estimation of dietary intake of folate, vitamins B6 and B12, we compared measures of these vitamins by the FFQ and plasma concentrations among 87 male volunteers aged 40-89 years in the Japan Public Health Center-based prospective study (JPHC Study). No men used folate, vitamins B6 or B12 as supplements. There was a moderate association between energy-adjusted dietary intake and plasma concentration for folate and vitamin B6. The Spearman correlation coefficient was 0.26 and 0.23, respectively, in the total samples. These correlation coefficients were slightly higher when men in the Ishikawa PHC area were excluded from the analysis; the correlation coefficient was 0.29 for folate and 0.26 for vitamin B6. No significant correlation was found between dietary vitamin B12 intake and serum B12 concentration; the correlation coefficient was 0.06 in the total sample and 0.15 when the Ishikawa men were excluded from the analysis. In conclusion, we found that the FFQ used for the 5-year follow-up survey of JPHC Study could reasonably rank individuals by dietary intake of folate and vitamin B6, but not vitamin B12, among Japanese community-dwelling population samples.

Diet Records↗

PubMed2003

Respiratory symptoms and pulmonary function among school-age children in the Aral Sea region.

The saline Aral Sea in central Asia was once the 4th largest inland lake in the world. Desiccation of the Aral Sea as a result of diversion of inflow for irrigation has resulted in significant adverse health effects among residents of surrounding areas. This study was conducted to examine respiratory symptoms and function among children who lived in "the heavily affected disaster zone" (i.e., within 200 km of the Aral Sea), by comparing them with children who lived in "the slightly affected disaster zone" (i.e., located approximately 500 km from the Aral Sea). A questionnaire-based interview was conducted among 383 students 6-15 yr of age who lived in the study area and 432 students who lived in the reference area. Pulmonary function tests were completed by 337 children in the study area and 417 children in the reference area. Prevalence of current cough and current wheezing was higher among the study group participants. Percentage of predicted forced vital capacity (FVC% predicted) was lower in the study group (median = 96.6%) than in the reference group (median = 100.5%), and prevalence of restrictive pulmonary dysfunction was higher in the study group (10.6%) than in the reference group (2.6%). Multivariate analysis indicated that FVC% predicted was lower among females and in the study area, but was not associated with socioeconomic factors.

Adolescent↗

PubMed2002

Circadian variation of blood pressure and endothelial function in patients with essential hypertension:a comparison of dippers and non-dippers.

OBJECTIVES: The purpose of this study was to evaluate the relationship between the circadian blood pressure (BP) rhythm and endothelial function in patients with essential hypertension. BACKGROUND: Hypertension is associated with alterations in resistance artery endothelial function. Patients with a non-dipper circadian pattern of BP have a greater risk of cerebrovascular and cardiovascular complications than do patients with a dipper circadian pattern. METHODS: We evaluated the forearm blood flow (FBF) response to intra-arterial acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, infusion in 20 patients with non-dipper hypertension and 20 age- and gender-matched patients with dipper hypertension. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The 24-h systolic BP, as well as nocturnal systolic and diastolic BPs were higher in non-dipper patients than in dipper patients. The 24-h urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was lower in non-dippers than in dippers. The response of FBF to ACh was smaller in non-dippers than in dippers (25.1 +/- 3.1 vs. 20.2 +/- 3.0 ml/min/100 ml tissue, p < 0.05). The FBF response to ISDN was similar in dippers and non-dippers. The FBF response to ACh was similar in the two groups following intra-arterial infusion of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dippers compared with patients who have dipper hypertension.

Acetylcholine↗

PubMed2002

Vegetables, fruit and risk of gastric cancer in Japan: a 10-year follow-up of the JPHC Study Cohort I.

The association between vegetables and fruit consumption and gastric cancer risk was investigated in a population-based prospective study in 4 public health center areas in Japan. Dietary and other exposure data were obtained in 1990 from a cohort of 19,304 men and 20,689 women with a self-administered questionnaire. After 10 years of follow-up, a total of 404 cases of gastric cancer were documented among them. After adjustment for age, gender, areas and other potential confounding factors and after exclusion of the cases diagnosed in first and second follow-up years, the relative risk associated with intake 1 or more days per week compared to less than 1 day per week was 0.64 (95% CI 0.45-0.92) for yellow vegetable, 0.48 (95% CI 0.25-0.89) for white vegetable and 0.70 (95% CI 0.49-1.00) for fruit. Relative risks associated with quintile of total vegetable consumption were 1.00, 0.86, 0.75, 0.90 and 0.75 (p for trend = 0.17). In the differentiated type of gastric cancer, the association became clearer: 1.00, 0.96, 0.78, 0.88 and 0.53 (p for trend = 0.03). This prospective study suggests that vegetable and fruit intake, even in low amounts, is associated with a lower risk of gastric cancer. Although no striking differences in the association were seen between cardia and noncardia cancer, an inverse association was higher in differentiated rather than in undifferentiated types of gastric cancer.

Adult↗

PubMed2002

Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type.

The effect of cigarette smoking or alcohol consumption on the risk of gastric cancer has not been clarified. We investigated this relationship, considering the anatomic subsite and histologic type of gastric cancer. A total of 19,657 men (aged 40-59 years at baseline), who responded to the baseline questionnaire and reported no serious illness at that time, were followed for 10 years, from January 1990 to December 1999. Gastric cancer was confirmed histologically in 293 men. Smoking was associated with an increased risk of the differentiated type of distal gastric cancer; compared to the group who never smoked, the adjusted rate ratios (RRs) of gastric cancer for past and current smokers were 2.0 (95% CI 1.1-3.7) and 2.1 (95% CI 1.2-3.6), respectively. No association was observed between cigarette smoking and risk of the undifferentiated type of distal gastric cancer except for a suggestive association with cardia cancer. For alcohol consumption, elevated risk was suggested only for cardia cancer of all histologic types, though the relationship failed to reach significance. Among those who drank alcohol at least once per week, RRs for ethanol intake of 2.7-161.0, 162.0-322.0 and 322.5+ g/week compared to those who drank 0-3 times/month were 2.5 (95% CI 0.7-9.5), 3.3 (0.9-11.6) and 3.0 (0.8-11.1), respectively (p(trend) = 0.66). In conclusion, our results confirm that smoking is related to gastric cancer of the differentiated type. Further studies with more cases are needed to detect a positive association between cigarette smoking or alcohol consumption and cardia cancer.

Adult↗

PubMed2002

A new class of potent nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists: design and synthesis of 2-phenylimidazo[1,2-a]pyrimidin-5-ones.

The design and synthesis of a new class of nonpeptide luteinizing hormone-releasing hormone (LHRH) receptor antagonists, the 2-phenylimidazo[1,2-a]pyrimidin-5-ones, is reported. Among compounds described in this study, we identified the potent antagonist 15b with nanomolar in vitro functional antagonism. The result might suggest that the heterocyclic 5-6-ring system possessing a pendant phenyl group attached to the five-membered ring is the important structural feature for a scaffold of small molecule LHRH antagonists.

Binding, Competitive↗

PubMed2002

A flow method with photocatalytic oxidation of dissolved organic matter using a solid-phase (TiO2) reactor followed by amperometric detection of consumed oxygen.

A photocatalytic sensor for the determination of chemical oxygen demand (COD) using titanium dioxide, based on the use of a pair of oxygen electrodes and flow injection analysis, is described. The measuring principle is based on the direct determination of the oxygen concentration change resulting from photocataltic oxidation of organic compounds. One of the two oxygen electrodes, the reference oxygen electrode, was utilized to measure the reference signal responding only to oxygen present in the injected samples. Oxygen consumption due to the TiO2-catalyzed photochemical oxidation of organic compounds in samples was monitored with the working oxygen electrode. The COD value of this sensor was calculated as the difference of the currents at reference and working oxygen electrodes, respectively. The operation characteristics of the sensor are demonstrated using artificially treated wastewater as a substrate. The sensor was also applied to the determination of COD in real water samples from dam reservoirs (n = 20) all over Japan. The results were in good agreement with those from the conventional COD methods (i.e., permanganate and dichromate methods).

Electrochemistry↗

PubMed2002

Site-directed mutagenesis for cysteine residues of cobalt-containing nitrile hydratase.

Three cysteine residues, which are completely conserved among alpha-subunits in all nitrile hydratases, are thought to be the ligands of a metal ion in the catalytic center of this enzyme. These cysteine residues (i.e. alpha C102, alpha C105 and alpha C107) in the high-molecular-mass nitrile hydratase (H-NHase) of Rhodococcus rhodochrous J1 were replaced with alanine by site-directed mutagenesis using the R. rhodochrous ATCC12674 host-vector system, and the resultant transformants were investigated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for the cell-free extracts of each mutant transformant revealed that four mutant transformants (i.e. alpha C105A, alpha C107A, alpha C102A/C105A and alpha C105A/C107A) showed predominant alpha- and beta-subunit protein bands with a mobility identical to those of the native H-NHase, while three mutant transformants (i.e. alpha C102A, alpha C102A/C107A and alpha C102A/C105A/C107A) did not produce the corresponding proteins. The purified former four mutant enzymes showed neither enzymatic activity nor the maximum absorption at 410 nm which was detected in the wild type H-NHase. They also did not contain cobalt ions. Based upon these findings, these three cysteine residues were found to be essential for the active expression of H-NHase.

Amino Acid Sequence↗

PubMed2002

Urinary level of 1,N(6) -ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and omega 6-polyunsaturated fatty acid intake in postmenopausal Japanese women.

Excretion of 1,N(6)-ethenodeoxyadenosine (epsilon dA), a marker for lipid peroxidation (LPO)-derived DNA damage was analyzed in urine of nonsmoking postmenopausal women participating in a dietary intervention trial in Northern Japan. Hereby the efficacy of dietary consultation in reducing salt and increasing vitamin C and carotenes during 1 year was estimated. Thirty postmenopausal women, 60-69 years of age, from the intervention group and 30 age-matched women from the control group were randomly selected. The subjects completed a self-administered diet history questionnaire and in the pre- and post-intervention period 48 hr urine and fasting blood samples were collected. epsilon dA in urine was analyzed by an immuno-precipitation-high performance liquid chromatography-fluorescence detection method. epsilon dA excretion (/48 hr) in the 59 postmenopausal Japanese women with complete urine collection ranged from 12-226 pmol at the pre-intervention. At the pre-intervention, epsilon dA excretion was positively associated with urinary salt excretion (R = 0.33, p = 0.01) and omega-6 polyunsaturated fatty acid intake (%energy value, R = 0.28, p = 0.03) in the 59 women. The average epsilon dA excretion in the intervention group was 61 pmol at pre-intervention and 44 pmol at post-intervention (p = 0.14). In the control group, it was 58 pmol at pre-intervention and 75 pmol at post-intervention (p = 0.24). During the intervention period, 18/29 (62%) of the subjects in the intervention group exhibited the decreased excretion and 10/26 (38%) in the control group (p = 0.08). Results from this pilot study suggest urinary epsilon dA as a potential biomarker of DNA damage possibly derived from salt-induced inflammation and LPO; further exploration of epsilon dA in human biomonitoring studies is warranted.

Aged↗

PubMed2002

Cigarette smoking and subsequent risk of lung cancer by histologic type in middle-aged Japanese men and women: the JPHC study.

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population-based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non-smokers was 4.5 [95% confidence interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI: 4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI: 0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma.

Adenocarcinoma↗

PubMed2002

Cytoplasmic expression of laminin gamma2 chain correlates with postoperative hepatic metastasis and poor prognosis in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The laminin gamma2 chain is involved in tumor invasion and metastasis, but the significance of laminin gamma2 chain expression remains unclear in patients with pancreatic carcinoma. METHODS: Laminin gamma2 chain expression was examined immunohistochemically in 48 patients with pancreatic ductal adenocarcinoma who were followed closely to elucidate the correlations between clinicopathologic factors, postoperative recurrence, and overall survival. Prognostic factors for postoperative survival were examined comparing clinicopathologic factors and laminin gamma2 chain expression. RESULTS: Two different staining patterns of laminin gamma2 chain expression, cytoplasmic expression and basement membrane expression, were detected in tumors from all 48 patients. Tumors were then classified into two types according to the dominant pattern of laminin gamma2 chain expression: the cytoplasmic expression dominant type (CYT; n = 26 patients) and the basement membrane expression dominant type (BM; n = 22 patients). Tumor differentiation was associated statistically with the BM type of laminin gamma2 chain expression (P = 0.0002). The CYT type of laminin gamma2 chain expression was associated significantly with the occurrence of postoperative hepatic metastasis (P = 0.0011) and also was the strongest predictive factor for poorer overall survival in patients with pancreatic ductal adenocarcinomas (P = 0.0161). CONCLUSIONS: The cytoplasmic expression of the laminin gamma2 chain represents the high invasive potential of the tumor and is correlated with distant metastasis, especially hepatic metastasis, and with a poorer prognosis in patients with pancreatic ductal adenocarcinoma.

Adult↗

PubMed2002

Comparison of cause-specific mortality between respondents and nonrespondents in a population-based prospective study: ten-year follow-up of JPHC Study Cohort I. Japan Public Health Center.

To evaluate the magnitude and duration of the "healthy volunteer effect" (HVE) in a middle-aged general population in Japan, we followed 54,396 subjects (26,998 men, 27,398 women) of the JPHC Study Cohort I from 1990 through 1999, and compared cause-specific mortality between respondents (79%) and nonrespondents to a baseline questionnaire survey. Age and area-adjusted RRs of mortality were higher among nonrespondents for all causes (2.02, 95% CI = 1.83-2.24), all cancers (1.43, 1.20-1.71), all circulatory system diseases (2.26, 1.86-2.74), and cerebrovascular disease (2.73, 2.04-3.66) in men, and 1.63 (1.39-1.92), 1.22 (0.94-1.58), 1.53 (1.07-2.20), and 1.65 (1.02-2.65), respectively, in women. These effects were not observed for ischemic heart disease. RR elevation for cancer was observed only in the first 2 years of follow-up (4.14, 2.74-6.26 versus 1.14, 0.93-1.40 after 2 years), while that for cerebrovascular disease was relatively stable for the entire period. In conclusion, HVE differed according to the causes and length of follow-up.

Adult↗

PubMed2002

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension.

BACKGROUND: Both obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension. METHODS: We measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 microg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 microg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 +/- 3.6 kg/m2). Fifteen healthy Japanese normotensive individuals were recruited as a control group. RESULTS: In obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 +/- 15.0 to 73.2 +/- 13.5 kg (P < .01), the mean blood pressure from 118.4 +/- 8.7 to 105.7 +/- 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 +/- 22.8 to 64.8 +/- 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 +/- 0.76 to 4.67 +/- 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 +/- 0.48 to 3.29 +/- 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of NG-monomethyl-L-arginine (8 micromol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction. CONCLUSIONS: The present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.

Acetylcholine↗

PubMed2002

Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast: a prospective observational study.

We have already reported invasive ductal carcinomas (IDCs) with fibrotic focus (FF) to be associated with significantly poorer survival than IDCs without FF. The purpose of this study was to prospectively investigate the effect of the presence of FF on the outcomes of 439 patients with IDCs to confirm the prognostic significance of FF, by the multivariate analysis, employing the Cox proportional hazard regression model, as compared with well-known clinicopathological parameters. We also precisely evaluated the prognostic significance of FF from the viewpoint of FF characteristics. The present study demonstrated that the presence of FF is a very useful parameter predicting tumor recurrence (TR), as well as initial distant organ metastasis (IDOM), in lymph node-negative IDCs (P =.024 and P =.026) and in IDCs positive for either or both estrogen receptor (ER) or progesterone receptor (PR) (P =.007 and P =.015), respectively. In addition, FF of >8 mm in diameter was found to be an independent prognostic parameter for TR and IDOM in lymph node-negative patients and patients with IDC positive for either or both ER or PR (P =.005 and P =.018). We conclude that the presence of FF is a very important histologic prognostic parameter for patients with IDCs of the breast.

Adult↗

PubMed2002

Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer.

Patients with squamous-cell carcinoma in the head and neck (HNSCC) often develop second primary esophageal squamous-cell carcinomas (ESCC). In addition, widespread epithelial oncogenic alterations are also frequently observed in the esophagus and can be made visible as multiple Lugol-voiding lesions (multiple LVL) by Lugol chromoendoscopy. Multiple occurrences of neoplastic change in the upper aerodigestive tract have been explained by the concept of 'field cancerization', usually associated with repeated exposure to carcinogens such as alcohol and cigarette smoke. However, the etiology of second ESCC in HNSCC patients remains unclear and acetaldehyde, the first metabolite of ethanol, has been implicated as the ultimate carcinogen in alcohol-related carcinogenesis. We first investigated the relation between second ESCC and multiple LVL in 78 HNSCC patients. Multiple LVL and second ESCC were observed in 29 (37%) and 21 (27%) patients, respectively. All of the second ESCC were accompanied by multiple LVL. This may indicate that episodes of multiple LVL are precursors for second ESCC. We then examined the association of multiple LVL with the patients' characteristics, including genetic polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2). We also investigated acetaldehyde concentrations in the breath of 52 of the 78 patients. All the patients with multiple LVL were both drinkers and smokers. Multivariable logistic analysis showed that the inactive ALDH2 allele (ALDH2-2) was the strongest contributing factor for the development of multiple LVL (odds ratio 17.6; 95% confidence intervals 4.7-65.3). After alcohol ingestion, acetaldehyde in the breath was elevated to a significantly higher level in all patients with the ALDH2-2 allele than in those without it. The high levels of breath acetaldehyde were significantly modified by the slow-metabolizing ADH3-2 allele. These results reveal strong evidence for a gene-environmental interaction between the ALDH2-2 allele and alcohol consumption, for the risk of developing multiple LVL, resulting in the development of second ESCC in patients with HNSCC. Ultimately, increased local acetaldehyde exposure thus appears to be a critical determinant of the phenomenon of 'field cancerization'.

Alcohol Drinking↗