Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Prevalence of tobacco dependence and associated factors in China: Findings from nationwide China Health Literacy Survey during 2018-19.

Background: Tobacco dependence is the key barrier to successful smoking cessation. However, little is known about its prevalence, sociodemographic characteristics and determinants. We aimed to estimate the prevalence, associated factors and burden of tobacco dependence in China. Methods: During 2018-2019, the nationally representative 2018 China Health Literacy Survey (2018 CHLS) invited 87,708 participants to participate using a multistage stratified sampling method from 31 provinces (or equivalent) in mainland China, and 84,839 participants aged 20-69 with valid data were included in the analysis. We diagnosed tobacco dependence based on international criteria (ICD-10, DSM-4) and tailored to Chinese population according to China Clinical Guideline for Tobacco Cessation (2015 version). The prevalence of tobacco dependence was estimated overall and by sociodemographic factors. The Logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tobacco dependence and success of smoking cessation (being ex-smokers), with different levels of adjustment. These were used to estimate the total number of adults who were tobacco dependent in China. Findings: In China, the estimated prevalence of current smoking was 25.1%, significantly higher in men than in women (47.6% vs 1.9%). The prevalence of current smoking varied approximately 3-fold (12.9% to 37.9%) across 31 provinces of China. Among general population aged 20-69 years, the prevalence of tobacco dependence was 13.1% (95% CI:12.2-14.1). Among current smokers, the prevalence of tobacco dependence was 49.7% (46.5-52.9%), with no difference between men and women (49.7% vs 50.8%). The prevalence of tobacco dependence was associated significantly with smoking intensity, defined by pack-years (1.62 [1.54-1.70] per 10 pack-years), cigarettes smoked per day (2.01 [1.78, 2.27] per 10 cigarettes), and smoking starting age (0.93 [0.90, 0.97] per 5 years). Given smoking intensity, the prevalence of tobacco dependence also varied by age, gender, certain socioeconomic status and regions. Compared with those without tobacco dependence, ever smokers with tobacco dependence were less likely to be ex-smokers (2.88, 2.59-3.21). In China, 183.5 (170.4-197.4) million adults (177.5 million were men) were tobacco dependent in 2018. Interpretation: In China, tobacco dependence is highly prevalent, with approximately half of current smokers being addictive, highlighting the need for coordinated effort to improve awareness, diagnosis and treatment of tobacco dependence. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), National Key R&D Program of China (grant no 2017YFC1309400), and National Natural Science Foundation of China (grant no 81720108001). Note: Chinese translation of abstract is available in appendix section.

The experience of tobacco withdrawal symptoms among current smokers and ex-smokers in the general population: Findings from nationwide China Health Literacy Survey during 2018-19.

Objective: To clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking. Methods: We included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018-2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20-69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables. Results: Among ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62-1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86-2.27) were less likely to successfully quit. Conclusions: The clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.

Factors related to age at natural menopause in China: results from the China Kadoorie Biobank.

OBJECTIVES: The aim of this study was to investigate the potentially modifiable factors affecting age at natural menopause (ANM) in Chinese women. METHODS: We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million (0.3 million women) Chinese adults aged 30 to 79 from 2004 to 2008. Multinomial logistic regression models were used to examine the relationships between ANM and various factors recorded at baseline. RESULTS: Among 87,349 postmenopausal women, the mean ANM (SD) was 48.7 (4.3) years. Older age, being a housewife, earlier menarche, and passive smoking were associated with both premature menopause (PM, ie, ANM <40 years) and early menopause (EM, ie, ANM between 40 and 44 years). A higher odds for EM was observed in women who were widowed (odds ratio: 1.10, 95% confidence interval: 1.04-1.16), had spontaneous abortions (1.33 [1.05-1.69]), current regular smoking (1.19 [1.07-1.37]), and frequent spicy food intake (1.11 [1.05-1.08]). Higher socioeconomic status; later first birth; more live births and induced abortions; longer breastfeeding; tea drinking, as well as intakes of meat, fruits, dairy, and soybean products; and increased body mass index gain were inversely associated with PM and/or EM. In contrast, women who had more pregnancies, occasional alcohol drinking, higher levels of physical activity or body mass index, vitamin intake, and hypertension were more likely to have a later age at menopause (LM, ie, ANM ≥53 years). CONCLUSIONS: This large epidemiological study found a wide range of sociodemographic, lifestyle, dietary, and reproductive factors related to PM, EM, and LM in Chinese women.

Age at natural menopause and associated factors in adult women: Findings from the China Kadoorie Biobank study in Zhejiang rural area.

OBJECTIVES: To investigate the factors associated with age at natural menopause in a large population of Chinese adult women. METHODS: This cross-sectional study was part of the baseline survey of China Kadoorie Biobank in Zhejiang Province. A total of 17,076 postmenopausal women were included in the present study. Relevant data of socio-demographic, lifestyle, dietary and reproductive characteristics were collected. Multinomial logistic regression models were used to examine the associated factors of age at natural menopause with adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were reported. RESULTS: The mean age at natural menopause was 48.94 years, with 3.40% of the women experienced premature menopause and 6.75% early menopause. Younger age, higher education, consumption of meat (1-3 days per week) and increased parity were associated with late menopause. Current smoking, underweight, higher physical activity, consumption of sea food (1-3 days per week), fresh eggs (≥4 days per week), fresh fruits (≥1 day per week), taking vitamins, experiencing severe food shortage, earlier age at menarche and older age at first birth were associated with earlier age at natural menopause. CONCLUSIONS: These results suggest that certain factors involved with socio-demographic, lifestyle, dietary and reproductive characteristics are related to the age at natural menopause in Chinese women.

Implementation of the World Health Organization Framework Convention on Tobacco Control in China: An arduous and long-term task.

China is the largest producer and consumer of tobacco in the world. Consequently, the burden of tobacco-related diseases in China is enormous. Implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) may lead to a significant reduction in tobacco-related morbidity and mortality both in China and globally. In this review, the authors summarize the epidemic of tobacco use and the progress made in implementing the WHO FCTC, including the promotion of legislation for smoke-free public places; smoking-cessation assistance; labeling of tobacco packaging; enforcement of bans on tobacco advertising, promotion, and sponsorship; increased taxes on tobacco products; increased tobacco prices; improvements in public awareness of the dangers of smoking; and identifying the barriers to implementing effective tobacco-control measures in China. Since the WHO FCTC officially took effect in China on January 9, 2006, China has taken some important steps, especially in promoting legislation for smoke-free public places. Because tobacco permeates the fabric of society, business, commerce, and politics in China, commitments and actions from the government are crucial, and implementing the WHO FCTC in China will be an arduous and long-term task.

Emerging tobacco-related cancer risks in China: A nationwide, prospective study of 0.5 million adults.

BACKGROUND: In China, cigarette consumption has increased substantially since the 1980s, almost exclusively in men. This study was aimed at assessing the emerging cancer risks. METHODS: A nationwide, prospective study recruited 210,259 men and 302,632 women aged 30 to 79 years from 10 areas of China from 2004 to 2008; approximately 18,000 incident cancers were recorded during 7 years of follow-up. Cox regression yielded adjusted risk ratios (RRs) comparing smokers (including those who had stopped because of illness but not those who had stopped by choice) with never-smokers. RESULTS: Among men, 68% were smokers; their overall cancer risk was significantly increased (RR, 1.44; 95% confidence interval [CI], 1.37-1.53), and it was greater in urban (RR, 1.55; 95% CI, 1.41-1.70) than in rural areas (RR, 1.39; 95% CI, 1.30-1.49). This excess accounted for 23% of all cancers between the ages of 40 and 79 years, with significantly elevated risks of lung cancer (RR, 2.51; 95% CI, 2.18-2.90), liver cancer (RR, 1.32; 95% CI, 1.12-1.54), stomach cancer (RR, 1.34; 95% CI, 1.16-1.55), esophageal cancer (RR, 1.47; 95% CI, 1.24-1.73), and an aggregate of 5 other minor sites (RR, 1.52; 95% CI, 1.25-1.86). For lung cancer, the RRs were much greater for nonadenocarcinoma (RR, 5.83; 95% CI, 5.02-6.77) than for adenocarcinoma (RR, 1.78; 95% CI, 1.36-2.34). Among exsmokers (6.7%) who had stopped by choice, there was little excess cancer risk approximately 15 years after quitting. Among the few female smokers (3%), the overall cancer risk was also significantly increased (RR, 1.42; 95% CI, 1.28-1.57). Smoking was estimated to cause approximately 435,000 new cancers per year in China (approximately 360,000 in men and approximately 75,000 in women). CONCLUSIONS: In China, smoking now causes a quarter of all adult male cancers. High male uptake rates before the age of 20 years and nearly universal use of cigarettes foreshadow substantial tobacco-attributed risks in China unless there is widespread cessation.

[The China Kadoorie Biobank: related methodology and baseline characteristics of the participants].

OBJECTIVE: To study the separate and combined effects of environment, lifestyle, physical characteristics, blood biomarkers and genetic factors on aetiology of major chronic diseases in adult Chinese. METHODS: China Kadoorie Biobank (CKB) is a large blood-based prospective cohort study. The baseline survey took place in 5 urban and 5 rural areas across China during 2004-2008, with collection of data through questionnaire, physical examination and blood samples. Following the baseline survey, 5% of the randomly selected participants were surveyed in 2008, and repeated every 4-5 years. All participants would be followed for cause-specific mortality and morbidity through registries and for any hospital admission through linkages with health insurance databases. RESULTS: Overall, 512 891 adults aged 30-79 years (mean 51.5) were recruited, including 41.0% men and 55.9% from rural areas. Blood collection was successfully done in 99.98% of the participants. The prevalence of current regular smoking was 61.3% in men and 2.4% in women. The prevalence of regular alcohol consumption (i.e., weekly) was 33.4% in men and 2.1% in women. At the baseline, 41.8% of men and 45.3% of women were overweight or obese (i.e., BMI≥24.0 kg/m2) and 32.2% of men and 30.2% of women were hypertensive (i.e., SBP≥140 mm Hg or DBP≥90 mm Hg). For each of the main baseline variables, there were large variations on age, sex and areas of study. CONCLUSION: CKB seemed to be a powerful and rich resource in studying the environmental and genetic determinants of major chronic diseases in the Chinese population.

Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor ß receptor type II as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis.

BACKGROUND: The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis. METHODS: We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed. RESULTS: Minichromosome maintenance complex component 2 (MCM2) and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis (HR = 0.63, 95%CI: 0.46 - 0.86). Cyclin A expression above the median predicted an improved patient prognosis (HR = 0.71, 95%CI: 0.53 - 0.95). For mismatch repair deficiency and transforming growth factor ß receptor type II (TGFBRII) overexpression there was a borderline association with a poorer prognosis (HR = 0.69, 95%CI: 0.46 - 1.04 and HR = 2.11, 95%CI: 1.02 - 4.40, respectively). No apparent associations were found for other markers. CONCLUSION: This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.

[Body mass index and mortality from ischaemic heart disease in China: a 15-year prospective study on 220 000 adult men].

OBJECTIVE: To assess the relationship between body mass index (BMI) and ischaemic heart disease (IHD) mortality, especially in populations with low mean BMI levels. METHODS: We examined the data from a population-based, prospective cohort study of 220 000 Chinese men aged 40 - 79, who were enrolled in 1990 - 1991, and followed up ever since to 1/1/2006. Relative risks of the deaths from IHD by the baseline BMI were calculated, after controlling age, smoking, and the other potential confounding factors. RESULTS: The mean baseline BMI was 21.7 kg/m(2), and 2763 IHD deaths were recorded during the 15-year follow-up (6.8% of all deaths) program. Among men without prior vascular diseases at baseline, there was a J-shaped association between BMI and IHD mortality. When baseline BMI was above 20 kg/m(2), there was a strongly positive association of BMI with IHD risk, with each 5 kg/m(2) higher in BMI associated with 21% (95%CI: 9% - 35%, P = 0.0004) higher IHD mortality. Below this BMI range, the association appeared to be reverse, with the risk ratios as 1.00, 1.11, and 1.14, respectively, for men with BMI 20 - 21.9, 18 - 19.9, and < 18 kg/m(2). The excess IHD risk observed at low BMI levels persisted after restricting analysis to never smokers or excluding the first 3 years of follow-up. CONCLUSION: Lower BMI was associated with lower IHD risk among people in the so-called 'normal range' of BMI values (20 - 25 kg/m(2)). However, below that range, the association might well be reversed.

[Relationship between smoking and risk of esophageal cancer in 103 areas in China: a large-scale case-control study incorporated into a nationwide survey of mortality].

OBJECTIVE: To examine the relationship between smoking and risk of esophageal cancer (EC), and present a theoretical framework of control selection in population-based case-control study which was incorporated into a nationwide retrospective survey of mortality in China. METHODS: A large-scale population-based case-control study was incorporated into the nationwide retrospective survey of mortality conducted 1989 - 1991 in 24 urban cities selected by non-random sampling and 79 rural counties selected from 3000 counties included in the 1973 - 1975 cancer distribution survey by random sampling during. A questionnaire survey was conducted by home visit to investigate the death causes and smoking history of 19 734 deceased male adults who died of esophageal cancer during 1986 - 1988 at the age >or= 35. Two control groups were set up to undergo questionnaire survey by home visit to investigate the smoking history of the deceased persons and the informants. Control group I included the surviving spouses or other informants of 31 989 male adults who died of non-malignant digestive diseases during 1986 - 1988 at the age >or= 35, and control group II included 104 846 male spouses of the deceased female adults who died of different causes during 1986 - 1989 at the age >or= 35. The relative risks and population smoking attributable risks for EC were calculated using non-conditional logistic model, and the results were compared for consistency between the analyses using two different control groups. RESULTS: The EC absolute death rates were higher in the smokers than in the non-smokers in all urban and rural area groups. The total EC absolute death rate per 1000 among the non-smokers vs. smokers was 0.37:0.65 in the urban areas, 0.99:1.29 in the inland rural areas, and 1.09:1.62 in the coastal rural areas in the control group I, and there was a similar trend in the control group II. There was a significant dose-response relation between the period of smoking and the death risk of EC and between the daily cigarette consumption and the death risk of EC. The risk ratios, for example, for cigarette per day < 10, 10-, and 20- in the urban men were 1.42, 1.82, 2.22 in the control group I (trend test P < 0.01), and 1.57, 1.95, and 3.18 in the control group II (trend test P < 0.01). CONCLUSION: Smoking is an important risk factor for mortality from EC in China. Investigating the surviving spouses of the deceased patients is a creative, effective, and feasible trial, with the prerequisite of whole population-based survey, in study of the main types of death and the relevant risk factors.

Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths.

Liver cancer and liver cirrhosis are common causes of death in China, where chronic lifelong hepatitis B infection is a major cause of both diseases. To help determine whether smoking is a cofactor for the development of liver cancer, we ascertained retrospectively the smoking habits of 36,000 adults who had died from liver cancer (cases) and 17,000 who had died from cirrhosis (controls) in 24 Chinese cities and 74 rural counties. Calculations of the smoker vs. nonsmoker risk ratios (RR) for liver cancer mortality were standardised for age and locality. Among adult men (aged 35+) there was a 36% excess risk of death from liver cancer among smokers (smoker vs. nonsmoker standardised risk ratio [RR] =1.36, with 95% confidence interval [CI] 1.29-1.43, 2p<0.00001; attributable fraction 18%). In the general male population this indicates absolute risks of death from liver cancer before age 70 of about 4% in smokers and 3% in nonsmokers (in the absence of other causes). Most liver cancer, however, occurs among the 10-12% of men with haematological evidence of chronic hepatitis B infection, so among them the corresponding risks would be about 33% in smokers and 25% in nonsmokers. The RR was approximately independent of age, was similar in urban and rural areas, was not significantly related to the age when smoking started but was significantly (p<0.001) greater for cigarette smokers than for smokers of other forms of tobacco. Among men who smoked only cigarettes, the RR was significantly (p<0.001 for trend) related to daily consumption, with a greater hazard among those who smoked 20/day (RR 1.50, 95% CI 1.39-1.62) than among those who smoked fewer (mean 10/day: RR=1.32, 95% CI 1.23-1.41). Smoking was also associated with a significant excess of liver cancer death in women (RR 1.17, 95% CI 1.06-1.29, 2p=0.003; attributable fraction 3%), but fewer women (17%) than men (62%) were smokers, and their cigarette consumption per smoker was lower. Among women who smoked only cigarettes, there was a significantly greater hazard among those who smoked at least 20/day (mean 22/day: RR=1.45, 95% CI 1.18-1.79) than among those who smoked fewer (mean 8/day: RR=1.09, 95% CI 0.94-1.25). These associations indicate that tobacco is currently responsible for about 50,000 liver cancer deaths each year in China, chiefly among men with chronic HBV infection.

Effects of retinoic acid on metastasis and its related proteins in gastric cancer cells in vivo and in vitro.

AIM: To investigate the effects of all-trans retinoic acid (ATRA) on metastasis and its related proteins in human gastric cancer cells in vivo and in vitro. METHODS: Gastric cancer cells, MGC80-3 and SGC-7901, were inoculated into spleen subcapsule of nude mice, respectively. Nude mice were administered with ATRA (0.7 mg/kg, ig) every other day. Six weeks later, nude mice were sacrificed. All the tumors formed in spleen and in liver were removed. Some of them were fixed, and then embedded. Others were kept in liquid nitrogen for further use. Expression level of proteins in tumor and in cell was analyzed by Western blot. Microvessel in tumor section was shown by immunohistochemistry and adhesive ability of cell to amnion was measured by adhesion assay. RESULTS: When inoculated nude mice were treated with ATRA, the xenograft tumors in spleen and metastatic tumors in liver were suppressed by 50 % respectively, and inhibition of microvessel formation in xenograft and metastatic tumors was also observed obviously. Although ATRA regulated expression of nm23 and mts1/p16 proteins at different patterns in vivo and in vitro, high ratio of nm23:mts1/p16 was in association with low adhesive activity of cells. In addition, ATRA induced ICAM-1 protein expression in vivo and in vitro. CONCLUSION: ATRA inhibits the growth of xenograft tumors and their metastasis to liver. This process may be associated with regulation of metastatic related proteins, including nm23, mts1/p16, and ICAM-1 in vivo and in vitro.

Anticancer effect of retinoic acid via AP-1 activity repression is mediated by retinoic acid receptor alpha and beta in gastric cancer cells.

To uncover the mechanisms relating to the anticancer effect of retinoic acids in gastric cancer cells, the mediation of activator protein-1 (AP-1) activity repression by retinoic acid receptors (RARs) was investigated. All-trans retinoic acid (ATRA) inhibited AP-1 activity in BGC-823 cells (RARalpha(+), RARbeta(+)), but not in MKN-45 cells (RARalpha(lo), RARbeta(-)). Transient transfection of RARbeta expression vector into MKN-45 cells significantly resulted in direct repression of AP-1 activity in a receptor concentration-dependent manner, and this could be strengthened by ATRA. Stable transfection of RARbeta into MKN-45 cells directly inhibited cell growth and colony formation, and ATRA also enhanced these effects. Transient transfection of RARalpha into MKN-45 cells however, displayed receptor concentration-dependent AP-1 activity inhibition only in the presence of ATRA. Stable transfection of RARalpha into MKN-45 cells resulted in ATRA-dependent inhibition of cell growth and colony formation. For AP-1 binding activity induced by TPA, the repressive effect of ATRA was only observed in BGC-823 and RARalpha and RARbeta stably transfected MKN-45 cells, but not in intact MKN-45 cells. This indicates the necessity for sufficient cellular RARalpha and/or RARbeta in order for AP-1 activity repression to occur. Deletion of DNA binding domain (DBD) of RARbeta, but not ligand binding domain (LBD), eliminated the anti-AP-1 function of RARbeta. It is therefore concluded that both RARalpha and RARbeta are mediators in the anticancer function of ATRA via AP-1 activity inhibition, and that RARbeta, not RARalpha, can inhibit AP-1 activity to a certain extent directly by itself. Thus DBD, not LBD, is critical for anti-AP-1 activity.