TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

BackgroundA pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer.MethodsA case-control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated.ResultsVariant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors.ConclusionsThis study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk

Rationales, design and recruitment of the Taizhou Longitudinal Study

<p/> <p>Background</p> <p>Rapid economic growth in China in the past decades has been accompanied by dramatic changes in lifestyle and environmental exposures. The burdens of non-communicable diseases, such as cardiovascular diseases, diabetes and cancer, have also increased substantially.</p> <p>Methods/design</p> <p>We initiated a large prospective cohort–the Taizhou Longitudinal Study–in Taizhou (a medium-size city in China) to explore the environmental and genetic risk factors for common non-communicable diseases. The sample size of the cohort will be at least 100,000 adults aged 30–80 years drawn from the general residents of the districts of Hailin, Gaogang, and Taixing (sample frame, 1.8 million) of Taizhou. A three-stage stratified sampling method will be applied. Baseline investigations include interviewer-administered questionnaire, anthropometric measurements, and collection of buccal mucosal cells and blood specimens. DNA will be extracted for genetic studies and serum samples will be used for biochemical examinations. A follow-up survey will be conducted every three years to obtain information on disease occurrence and information on selected lifestyle exposures. Study participants will be followed-up indefinitely by using a chronic disease register system for morbidity and cause-specific mortality. Information on non-fatal events will be obtained for certain major categories of disease (e.g., cancer, stroke, myocardial infarction) through established registry systems.</p> <p>Discussion</p> <p>The Taizhou Longitudinal Study will provide a good basis for exploring the roles of many important environmental factors (especially those concomitant with the economic transformation in China) for common chronic diseases, solely or via interaction with genetic factors.</p

Accelerating Decreases in the Incidences of Hepatocellular Carcinoma at a Younger Age in Shanghai Are Associated With Hepatitis B Virus Vaccination.

BackgroundRoutine vaccination of infants for protecting against hepatitis B virus (HBV) infection and its serious consequences, including hepatocellular cancer (HCC), has been carried out in Shanghai, China, since 1986. We therefore have examined the trend of HBV infection and HCC incidences before and after HBV vaccination over decades to assess the potential influences of the Shanghai HBV vaccination program.MethodsData on incidences of HBV infection and HCC were collected from the Shanghai Cancer Registry and the Shanghai HBV vaccination follow-up study. Joint-point regression and the Bayesian age-period-cohort statistical analysis methods were used.ResultsThe incidences of HBV infection dramatically declined from 23.09 and 1.13 per 100,000 for males and females in 2000 to 3.24 (-85.97%) and 0.22 (-80.53%) per 100,000 in 2014, respectively. Sero-epidemiological data from the sampling surveys during 20 years of follow-up showed that less than 1% of people undergoing HBV vaccination have a positive serum HBsAg. Consistently, the annual adjusted standardization rates (ASR) of HCC steadily fell from 33.38 and 11.65 per 100,000 for males and females in 1973 to 17.34 (-49.2%) and 5.60 (-51.9%) per 100,000 in 2014, respectively. The annual percentage change in overall HCC incidences is about -2%. HCC incidences in males at younger age groups (age &lt;50 years old), particularly in those with age &lt;34 groups, showed an accelerating decrease over time, whereas HCC incidences significantly declined in the female population across all age groups except for those under 19 years of age. The results supported that the universal HBV vaccination in newborns is easy to implement with high coverages and is effective for preventing both HBV infection and HCC in populations

Ataxia Telangiectasia-Mutated (ATM)Polymorphisms and Risk of Lung Cancer in a Chinese Population

BackgroundThe ataxia telangiectasia-mutated (ATM) gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs) with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer.MethodsA population-based case–control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR) and 95% confidence intervals (CIs). Adjusted models controlled for age, sex, and smoking status.ResultsThe study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06–2.35) and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08–2.08) in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT), ATMrs228589 (AA), and p53rs1042522 (CC) concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43–9.45) of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer.ConclusionThis study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples

Raw Garlic Consumption and Lung Cancer in a Chinese Population

BackgroundEvidence of anticancer properties of garlic for different cancer sites has been reported previously in in vitro and in vivo experimental studies but there is limited epidemiologic evidence on the association between garlic and lung cancer.MethodsWe examined the association between raw garlic consumption and lung cancer in a case-control study conducted between 2005 and 2007 in Taiyuan, China. Epidemiologic data was collected by face-to-face interviews from 399 incident lung cancer cases and 466 healthy controls. We used unconditional logistic regression models to estimate crude and adjusted ORs (aOR) and their 95% confidence intervals (CI). Adjusted models controlled for age, sex, average annual household income 10 years ago, smoking, and indoor air pollution.ResultsCompared with no intake, raw garlic intake was associated with lower risk of development of lung cancer with a dose-response pattern (aOR for &lt;2 times/week = 0.56; 95% CI, 0.39-0.81 and aOR for ≥2 times/week = 0.50; 95% CI, 0.34-0.74; Ptrend = 0.0002). Exploratory analysis showed an additive interaction of raw garlic consumption with indoor air pollution and with any supplement use in association with lung cancer.ConclusionsThe results of the current study suggest that raw garlic consumption is associated with reduced risk of lung cancer in a Chinese population.ImpactThis study contributes to the limited research in human population on the association between garlic and lung cancer and advocates further investigation into the use of garlic in chemoprevention of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 624-33. ©2016 AACR

TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population.

BACKGROUND: A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer. METHODS: A case-control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated. RESULTS: Variant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors. CONCLUSIONS: This study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk