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Biomedical subjects

Nobuyuki Hamajima

Publications and source records attributed to Nobuyuki Hamajima.

126 records · Page 7Linked to original sources
PubMed2000

A Model of Practical Cancer Prevention for Out-patients Visiting a Hospital: the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).

To promote a cancer prevention program at hospital, we started the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC) in 1988. Because patients visiting hospitals are very concerned not only about their own health condition but also practical way of disease prevention, we consider outpatients, especially those free of cancer, as ideal targets to make a model program and a practical cancer prevention strategy for general people. To confirm risk and protective effects of lifestyle factors like dietary habits, smoking and drinking, and exercise on cancer in Japanese, we have been undertaking large-scale case-referent comparative studies of main cancer sites (stomach, colorectal, lung, breast and uterine cancers) using the data generated by HERPACC. The risk of respiratory tract cancer was definitely elevated by habitual smoking and that of upper digestive tract cancer by combined habitual smoking and drinking. Frequent intake of raw vegetables and/or fruit in contrast reduced the risk of lung cancer among smokers. Current obesity was positively associated with risk of post-menopausal breast cancer, recently on the increase in Japan. However, all sites of cancer were linearly decreased with frequency of exercise in both males and females. Based on these pieces of evidence and other main results obtained from the HERPACC studies, prevention trials with provision of information about protective and risk factors for main sites of cancers to outpatients have been planned in parallel to continuation of HERPACC.

Journal Article↗
PubMedDate not supplied

Duplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP) for genotyping alcohol dehydrogenase beta subunit (ADH2) and aldehyde dehydrogenase 2 (ALDH2).

AIMS: Alcohol dehydrogenase beta subunit (ADH2) Arg47His and aldehyde dehydrogenase 2 (ALDH2) Glu487Lys were genotyped by a duplex polymerase chain reaction (PCR) with confronting two-pair primers (PCR-CTPP), which allows DNA amplification with one-tube PCR including eight primers, and subsequent electrophoresis. METHODS: Several PCR conditions were tested to establish the optimal conditions for distinguishing the allele-specific bands for the two polymorphisms. Under the optimal PCR conditions, 454 Japanese health check-up examinees were genotyped. RESULTS: The allele-specific bands were successfully amplified under the optimal conditions of the duplex PCR-CTPP. The genotype distributions were within the Hardy-Weinberg equilibrium. The bands produced by the duplex PCR-CTPP genotyping were clearer than those produced by PCR-CTPP, conducted solely for ADH2. CONCLUSIONS: ADH2 Arg47His and ALDH2 Glu487Lys were successfully genotyped by this newly developed duplex PCR-CTPP, an inexpensive and time-saving genotyping tool, which will be useful in epidemiological studies on alcoholism, as well as risk estimation of alcohol-related diseases.

Adult↗
PubMedDate not supplied

Triplex polymerase chain reactions with confronting two-pair primers (PCR-CTPP) for NQO1 C609T, GSTM1 and GSTT1 polymorphisms: a convenient genotyping method.

The polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is a time-saving and inexpensive genotyping method, which is applicable for most single nucleotide polymorphisms (SNPs). To date, we have established PCR-CTPP conditions for tens of SNPs, including duplex genotyping. This paper introduces triplex PCR-CTPP to simultaneously genotype three functional polymorphisms of carcinogen-detoxifying enzymes, NQO1 C609T, GSTM1 null, and GSTT1 null, all of which are reported to have a significant association with smoking-related cancers. We applied this method for 241 non-cancer patients to demonstrate the performance. Among the subjects, the genotype frequency of NQO1 C609T was 35.7% for CC, 44.4% for CT and 19.9% for TT. The null type frequencies of GSTM1 and GSTT1 were 53.4% and 44.0%, respectively. Their distributions were similar to those reported for Japanese by other studies. This is the first paper reporting the success of triplex PCR-CTPP. The polymorphisms applied are useful examples, which could be adopted not only for research purposes, but also for risk assessment of individuals exposed to carcinogenic substances, such as smokers. This convenient genotyping approach has advantages for application in cancer prevention, especially in the Asian Pacific region.

Asian People↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Anonymous Testing↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Anti-Bacterial Agents↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

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.

Case-Control Studies↗
PubMedDate not supplied

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.

Adolescent↗
PubMedDate not supplied

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.

Cytochrome P-450 CYP1A1↗
PubMedDate not supplied

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.

Adenocarcinoma↗
PubMedDate not supplied

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.

Adult↗