Associations of smoking with early- and late-onset colorectal cancer.

BACKGROUND: Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Smoking is an established risk factor of CRC risk, but evidence on its impact on early-onset CRC (EOCRC) risk is limited. We aimed to evaluate the association of smoking exposure with EOCRC and compare it with late-onset CRC (LOCRC). METHODS: Smoking history and other known or suspected CRC risk factors were ascertained in detail in personal interviews among 6264 CRC patients and 6866 controls (frequency matched for age, sex, and county of residence) who were recruited in 2003-2020 in the DACHS study (Darmkrebs: Chancen der Verhütung durch Screening [German]; Colorectal Cancer: Chances for Prevention Through Screening [English]), a population-based case-control study from Germany. Associations of smoking with EOCRC (<55 years, 724 cases, 787 controls) and LOCRC (≥55years, 5540 cases, 6079 controls) were estimated using multiple logistic regression. RESULTS: Smoking exposure was much higher among EOCRC cases than among controls, and strong associations of smoking were observed for both EOCRC and LOCR. Adjusted odds ratios for EOCRC and LOCRC were as follows: current smoking: 1.57 (95% confidence interval [CI] = 1.20 to 2.04, P < .001) and 1.46 (95% CI = 1.28 to 1.67, P < .001); former smoking: 1.39 (95% CI = 1.07 to 1.81, P = .01) and 1.24 (95% CI = 1.13 to 1.36, P < .001); per 10 pack-years: 1.15 (95% CI = 1.05 to 1.27, P < .001) and 1.05 (95% CI = 1.03 to 1.08, P < .001). These patterns were similar for colon and rectum cancer and for early- and late-stage CRC. CONCLUSION: Smoking is a strong risk factor for both EOCRC and LOCRC.

Is the association of overweight and obesity with colorectal cancer underestimated? An umbrella review of systematic reviews and meta-analyses.

Although high body-mass index (BMI) is associated with increased risk of developing colorectal cancer (CRC), many CRC patients lose weight before diagnosis. BMI is often reported close to diagnosis, which may have led to underestimation or even reversal of direction of the BMI-CRC association. We aimed to assess if and to what extent potential bias from prediagnostic weight loss has been considered in available epidemiological evidence. We searched PubMed and Web of Science until May 2022 for systematic reviews and meta-analyses investigating the BMI-CRC association. Information on design aspects and results was extracted, including if and how the reviews handled prediagnostic weight loss as a potential source of bias. Additionally, we analyzed how individual cohort studies included in the latest systematic review handled the issue. Overall, 18 reviews were identified. None of them thoroughly considered or discussed prediagnostic weight loss as a potential source of bias. The majority (15/21) of cohorts included in the latest review did not exclude any initial years of follow-up from their main analysis. Although the majority of studies reported having conducted sensitivity analyses in which initial years of follow-up were excluded, results were reported very heterogeneously and mostly for additional exclusions of 1-2 years only. Where explicitly reported, effect estimates mostly increased with increasing length of exclusion. The impact of overweight and obesity on CRC risk may be larger than suggested by the existing epidemiological evidence.

The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer.

OBJECTIVE: We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer (CRC) risk, to support effective risk communication for cancer prevention. METHODS: A healthy lifestyle score (HLS) was derived from 5 lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body adiposity. The association of lifestyle and polygenic risk score (PRS) (based on 140 CRC-associated risk loci) with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent (GRE), a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS. RESULTS: A higher HLS was associated with lower CRC risk (4,844 cases, 3,964 controls). Those adhering to all 5 healthy lifestyle factors had a 62% (95% CI 54%-68%) lower CRC risk than those adhering to ≤ 2 healthy lifestyle factors. The estimated effect of adherence to all 5 compared with ≤ 2 healthy lifestyle factors was as strong as the effect of having a 79 percentile (GRE 79, 95% CI 61-97) lower PRS. The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in ≥ 1 first-degree relative (P-interaction = 0.0013). CONCLUSIONS: A healthy lifestyle was strongly inversely associated with CRC risk. The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.

Assessment of Body Mass Index, Polygenic Risk Score, and Development of Colorectal Cancer.

Importance: Excess weight, the prevalence of which is high and increasing in many countries, is linked to multiple adverse health outcomes, including increased colorectal cancer (CRC) risk. Better communication of health risks associated with excess weight might support efforts of prevention. Objective: To evaluate the individual and joint associations of body mass index (BMI) and polygenic risk with CRC, to assess potential interactions among them, and to quantify by how much increased polygenic risk for CRC can be offset by having a BMI within reference range. Design, Setting, and Participants: This population-based case-control study was conducted in the Rhine-Neckar region of southwest Germany, with recruitment from 2003 to 2017. Participants with both risk factor and genetic information were included for analysis. Data analysis was conducted from December 8, 2021, to February 17, 2022. Exposures: BMI was calculated as self-reported weight in kilograms approximately 10 years before diagnosis or interview and current height in meters squared. A polygenic risk score (PRS) was built based on 140 CRC-related risk loci. Main Outcomes and Measures: Individual and joint associations of BMI and PRS with CRC were estimated using multiple logistic regression. Associations of excess weight with CRC were quantified by adjusted odds ratios (aORs) and genetic risk equivalents (GREs), the equivalent outcomes conveyed by defined differences in PRS percentiles. Results: Among 9169 participants (median [IQR] age, 69 [62-76] years; 5589 [61.0%] male participants) included, 5053 had CRC and 4116 did not. BMI of 30 or greater was associated with higher odds of having CRC compared with BMI less than 25 (aOR, 1.71; 95% CI, 1.49-1.97), independent of PRS levels (P for interaction = .45). Participants with BMI of 30 or greater and a PRS in the highest tertile had higher odds of CRC compared with participants with BMI less than 25 and a PRS in the lowest tertile (aOR, 3.82; 95% CI, 3.03-4.82). The estimated association of BMI greater than 30 with CRC risk was equivalent to that of having a 41 (95% CI, 29-53)-percentile higher PRS. BMI of 30 or greater was particularly associated with stage IV CRC (aOR, 2.21; 95% CI, 1.71-2.84). Conclusions and Relevance: These findings suggest that excess weight was associated with CRC regardless of PRS levels. The association of having a BMI within reference range may be similar to that of having a substantially lower polygenic risk for CRC.

Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk.

Background: Evidence is lacking on the impact of alcohol consumption on colorectal cancer (CRC) risk (overall and by age at diagnosis) by polygenic risk score (PRS) levels, and it is unclear how the magnitude of CRC risk associated with alcohol consumption compares to the magnitude of genetically determined risk. Methods: Multiple logistic regression was used to assess the association between alcohol consumption and colorectal cancer (CRC) across PRS levels based on 140 CRC-related loci among 5104 CRC cases and 4131 controls from a large population-based case-control study. We compared the effects for alcohol consumption and PRS on CRC risk using the "Genetic Risk Equivalent (GRE)" for effective risk communication. Specific analyses were conducted for early-onset CRC (EOCRC, <55 years) and late-onset CRC (LOCRC, ≥55 years). Findings: High alcohol consumption, and to a lower extent, also alcohol abstinence were associated with increased CRC risk. Compared to low alcohol consumption (0·1-<25 g/d), lifetime average alcohol consumption ≥25 g/d was more strongly associated with EOCRC [odds ratio (OR) 1·8, 95% confidence interval (CI) 1·2-2·8] than with LOCRC risk (OR 1·3, 95% CI 1·1-1·4) (P-value for interaction with age =0·011). Interactions between alcohol consumption and PRS did not reach statistical significance for either EOCRC or LOCRC risk. The estimated impact of high lifetime alcohol consumption on EOCRC was equivalent to the effect of having 47 percentiles higher PRS (GRE 47, 95% CI 12-82), stronger than the impact on LOCRC (GRE 18, 95% CI 8-29). Interpretation: Excessive alcohol use was strongly associated with EOCRC risk, independent of PRS levels. Abstaining from heavy drinking could reduce risk for CRC, in particular for EOCRC to an extent that would be equivalent to having a much lower genetically determined risk. Funding: The first author (X.C.) was supported by the Guangzhou Elite Project (GEP). The DACHS study was supported by grants from the German Research Council (BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6, CH 117/1-1, BR 1704/17-1, HO 5117/2-1) and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01GL1712).

Associations of Body Mass Index at Different Ages With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Given the established association of body mass index (BMI) with CRC risk and the increasing obesity prevalence among younger generations, we aimed to evaluate the association of BMI at different ages during early adulthood with early-onset CRC. METHODS: Among 6602 patients with CRC and 7950 matched controls who were recruited in 2003-2020 in the Darmkrebs: Chancen der Verhütung durch Screening study, a population-based case-control study from Germany, 747 patients and 621 controls were younger than 55 years and included in this analysis. Self-reported height and weight at ages 20 years and 30 years and at approximately 10 years before diagnosis or interview were recorded in personal interviews. Associations of BMI with early-onset CRC were estimated using multiple logistic regression. RESULTS: Compared with participants with BMI <25 kg/m2, those with BMI ≥30 kg/m2 (obesity) at ages 20 years and 30 years and approximately 10 years before diagnosis or interview had 2.56- (95% confidence interval, 1.20-5.44), 2.06- (confidence interval, 1.25-3.40), and 1.88- (95% confidence interval, 1.30-2.73) fold risk of early-onset CRC. The association of BMI with early-onset CRC risk was particularly pronounced among, and essentially restricted to, the majority of participants with no previous colonoscopy. CONCLUSIONS: Obesity at early adulthood is strongly associated with increased risk of early-onset CRC. German Clinical Trials Register ID: DRKS00011793.

Molecular mechanisms of Phytophthora sojae avirulence effectors escaping host recognition.

Phytophthora sojae is a well-known destructive oomycete pathogen, which causes soybean stem and root rot and poses a serious threat to global food security. Growing soybean cultivars with the appropriate resistance to P. sojae (Rps) genes are the primary management strategy to reduce losses. In most Phytophthora pathosystems, host resistance protein encoded by a specific R gene in the plant recognizes corresponding RxLR effector protein, encoded by an avirulence gene. This gene-for-gene relationship has been exploited to help breeders and agronomists deploy soybean cultivars. To date, 6 Rps genes have been incorporated into commercial soybean germplasm and trigger plant immunity in response to 8 P. sojae avirulence effectors. The incorporation of Rps genes in the soybean population creates selection pressure in favor of novel pathotypes of P. sojae. The 8 avirulence genes evolved to evade the host immune system, driven by genetic selection pressures. Understanding the evading strategies has important reference value for the prevention and control of Phytophthora stem and root rot. This investigation primarily highlights the research on the strategies of P. sojae avirulence effector evasion of host recognition, looking forward to creating durable resistance genes and thereby enabling successful disease management.

Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis.

INTRODUCTION: Incidence of colorectal cancer (CRC) in young adults has been increasing in recent decades in many countries for still widely unclear reasons. Suspected candidates include increasing prevalence of overweight and obesity, but specific evidence on their role for early-onset CRC (EOCRC) is sparse. We conducted a systematic review and meta-analysis to summarize available evidence on the association of body mass index (BMI) with EOCRC. METHODS: We systematically searched PubMed, EMBASE, and Web of Science up to February 2021 for studies that evaluated the association of BMI (before diagnosis but not near diagnosis) with CRC risk and reported specific results for EOCRC. Results from studies with similar BMI groupings were summarized in meta-analyses using random-effects models. RESULTS: Twelve studies were eligible and included. Results of 6 studies were pooled in meta-analyses, which yielded a higher risk of EOCRC for overweight and obesity (BMI ≥25 kg/m2) compared with normal weight (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.68). An increasing risk with increasing BMI was observed, with much higher risk for obesity (OR 1.88, 95% CI 1.40-2.54) than for overweight (OR 1.32, 95% CI 1.19-1.47). DISCUSSION: Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.

Short-course regimens of rifapentine plus isoniazid to treat latent tuberculosis infection in older Chinese patients: a randomised controlled study.

Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organization's End TB Strategy.In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50-69 years with LTBI in China.Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). In the modified intention-to-treat analysis on the completed doses, the cumulative rate of active disease during 2 years of follow-up was 1.21% (14 out of 1155) in the untreated controls, 0.78% (10 out of 1284) in the group that received the 8-week once-weekly regimen and 0.46% (six out of 1299) in the group that received the 6-week twice-weekly regimen. The risk of active disease was decreased, with an adjusted hazard ratio of 0.63 (95% CI 0.27-1.43) and 0.41 (95% CI 0.15-1.09) for the treatments, respectively. No significant difference was found in the occurrence of hepatotoxicity (1.02% (13 out of 1279) versus 1.17% (15 out of 1279); p=0.704).The short regimens tested must be used with caution among the elderly because of the high rates of adverse effects. Further work is necessary to test the ultrashort regimens in younger people with LTBI.

Reversion of QuantiFERON-TB Gold In-Tube test in individuals with and without prophylactic treatment for latent tuberculosis infection: A systematic review and meta-analysis.

OBJECTIVES: Reversion of tuberculosis (TB) infection testing has been suggested to be associated with prophylactic treatment efficacy. However, evidences based on randomized controlled study were sparse. METHODS: Studies on serial QuantiFERON-TB Gold In-Tube (QFT) test, among individuals with and without prophylactic treatment were identified in the databases of PubMed, MEDLINE and EMBASE up to 28 February 2018. The reversion rates were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS: A total of 52 eligible studies were included in the meta-analysis on QFT test reversion rate among participants with (20 studies) and without (32 studies) prophylactic treatment. Summarized reversion rate was found to be 24.9% (95% confidence interval [CI]: 18.4-32.9%) and 25.3% (95% CI: 19.6-32.0%) for those completed or without treatment, respectively. When the analysis was restricted to the participants completed treatment, higher summarized rate of QFT reversion was found among those with longer course therapy (9INH vs. the other regimens), studies from Asia (vs. Europe and America), and individuals with immunosuppression disorders (vs. general populations). CONCLUSIONS: Our results suggested that QFT reversion was frequently observed regardless of with or without prophylactic treatment. Serial QFT testing might be inappropriate for evaluating preventive treatment efficacy.

Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette-Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study.

The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guérin (BCG) booster vaccination in China was estimated using tuberculin skin testing (TST) and QuantiFERON-TB Gold assay (QFT) to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5-15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST (induration = 10 mm) and QFT positivity were 9.3% (264/2827) and 2.5% (71/2831), respectively. The rate of QFT indeterminate result was 2.2% (62/2831). The overall agreement between TST and QFT was low (concordance = 88.0%; ? coefficient = 0.125). Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26-2.31]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a twostep approach might be considered for TB infection testing among adolescents in China.

Tuberculosis infection in rural labor migrants in Shenzhen, China: Emerging challenge to tuberculosis control during urbanization.

During China's urbanization process, rural labor migrants have been suggested to be one important bridge population to change urban-rural distribution on tuberculosis (TB) burden. Aiming to estimate the prevalence of TB infection and to track the active disease development in rural labor migrants, a prospective study was conducted in Shenzhen city, southern China. TB infection was detected using interferon-γ release assay (IGRA). Here we mainly report the characteristics of TB infection in the study population based on the baseline survey. A total of 4,422 eligible participants completed baseline survey in July 2013. QuantiFERON (QFT) positivity rates 17.87% (790/4,422) and was found to be consistent with the local TB epidemic of the areas where the participants immigrated from. Age, smoking, residence registered place, and present of BCG scars were found to be independently associated with QFT positivity. Additionally, evidence for interaction between smoking and age was observed (p for likelihood ratio test < 0.001). Our results suggested that the development of TB control strategy including latent TB infection management should pay more attention to the rural flowing population due to their high mobility and higher prevalence of TB infection.

Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study.

BACKGROUND: The management of latent Mycobacterium tuberculosis infection is a new priority action for the WHO End Tuberculosis (TB) Strategy. However, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in China. Here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore the most suitable latent infection diagnostic approach. METHODS: A population-based multicentre prospective study was done in four sites in rural China, between 2013 and 2015. The baseline survey in 2013 measured the prevalence of latent tuberculosis infection using QuantiFERON-TB Gold In-Tube (QFT) and tuberculin skin test (TST) in eligible participants. During the follow-up phase between 2014-15, we assessed individuals who had tuberculosis infection at baseline (QFT-positivity or TST tuberculin reaction size [induration] of ≥10 mm) for the development of active disease through active case finding. Eligible participants included in follow-up survey had a birth date before June 1, 2008 (5 years or older in 2013), and continuous residence at the study site for 6 months or longer in the past year. Participants with current active tuberculosis at baseline survey were excluded. FINDINGS: Between Sept 1, 2013, and Aug 31, 2015, 7505 eligible participants (aged 5 years or older) were included in tuberculosis infection test positive cohorts (4455 were QFT positive, 6404 had TST induration ≥10 mm, and 3354 were positive for both tests) after baseline examination. During the 2-year follow-up period, 84 incident cases of active tuberculosis were diagnosed. Of participants who developed active tuberculosis, 75 were diagnosed with latent infection by QFT, 62 were diagnosed by TST, and 53 were diagnosed by both tests. An incidence rate of 0·87 (95% CI 0·68-1·07) per 100 person-years was observed for individuals who tested positive with QFT, 0·50 (0·38-0·63) per 100 person-years for those who tested positive with TST (p<0·0001), and 0·82 (0·60-1·04) per 100 person-years for those who tested positive with both tests. Male sex and a history of tuberculosis were significantly associated with increased risk of disease development with adjusted hazard ratios of 2·36 (95% CI 1·30-4·30) for male sex and 5·40 (3·34-8·71) for a history of tuberculosis. INTERPRETATION: Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. FUNDING: National Science and Technology Major Project of China, Program for Changjiang Scholars and Innovative Research Team in University of China, CAMS Innovation Fund for Medical Sciences, and Sanming Project of Medicine in Shenzhen.

A dose-response relationship of smoking with tuberculosis infection: A cross-sectional study among 21008 rural residents in China.

OBJECTIVES: China has high burden on both of tuberculosis (TB) and tobacco use. This study aims to explore the potential link between smoking and TB infection using baseline survey data of a large-scale population-based prospective study in rural China. METHODS: Between July 1 and Sept 30, 2013, based on the baseline survey of a population-based, prospective study in rural China, the relationship between smoking and TB infection, assessed by interferon-gamma release assays (IGRA), was investigated among the total study population and only among those smokers, respectively. RESULTS: A total of 21,008 eligible rural registered residents (≥ 5 years old) from 4 rural sites were included in the analysis. Ever-smokers were more likely to be QuantiFERON-TB Gold In-Tube (QFT) positive than never smokers with an adjusted odds ratio (OR) of 1.34 (95% confidence interval (CI): 1.21-1.49). Among ever smokers, a significant linear dose-response relation was observed between duration of smoking (by years) and QFT positivity (p < 0.001). Stratified analysis suggested that such an association was not influenced by gender and age. Evidence for interaction of smoking status with age was found. CONCLUSIONS: Our results provide further evidence to support smoking might increase host susceptibility to TB infection. Populations under high risk of infection, such as elderly smokers, should be prior to TB infection controlling under a premise of community level intervention.

Association of Body Mass Index with the Tuberculosis Infection: a Population-based Study among 17796 Adults in Rural China.

Body mass index (BMI) has been shown to be associated with host susceptibility to several infections. However, the link between BMI and the risk of tuberculosis (TB) infection has been sparsely studied in China and in worldwide. Based on the baseline survey of a population-based, prospective study in rural China, the association between BMI and TB infection among adults was estimated by means of cross-sectional analysis. TB infection status was tested using QuantiFERON-TB Gold In-Tube (QFT), a commercial of interferon-γ release assay (IGRA). Totally, 17796 eligible participants aged ≥18 years from 4 study sites, were included in the analysis. 21.76% (3873/17796) were observed to be QFT positive. Age and gender standardized prevalence ranged from 16.49% to 23.81% across the study sites. 42.19% study participants were obese/overweight with BMI ≥ 24.0 kg/m2. BMI ≥ 28.0 kg/m2 was observed to be independently associated with QFT positivity (adjusted odds ratio: 1.17, 95% confidence interval: 1.04-1.33). The strength of the association was found to be geographically diversity, which might be explained, at least partly, by the varied local TB epidemic status. Our results suggest that individuals with obesity might be one important target population for TB infection control in rural China.

Association between tuberculosis and circulating microRNA hsa-let-7b and hsa-miR-30b: A pilot study in a Chinese population.

Tuberculosis remains one of the world's deadliest communicable diseases. Limitations in the current diagnosis tools have heavily slowed down the step to eliminate TB. The objective of this study was to identify potential circulating miRNA associated with tuberculosis (TB) infection and disease development. Agilent human miRNA microarray was used to estimate the circulating levels of 1887 miRNAs among 34 study participants (10 patients with pulmonary TB, 13 controls with latent TB infection and 11 non-infected healthy controls). The identified miRNAs were subsequently verified by real-time qPCR. Target gene prediction and miRNA-gene network construction were further explored. A total of 119 miRNAs were identified to be in different levels between any two groups of the study population by microarray (Fold Change>2, p < 0.01). 11 most promising miRNAs were then selected for verification by real-time qPCR. The levels of hsa-let-7b-5p and hsa-miR-30b-5p were confirmed to be significantly up-regulated in pulmonary TB patients as compared to both control groups (p < 0.01). Caspase 3 was predicted to be one common target gene for these two miRNAs. None of the selected miRNA was confirmed to be related with the infection status. This pilot study suggested circulating hsa-let-7b and hsa-miR-30b might be associated with TB development by regulating the target genes involved in TLR-NF-kB mediated signal pathway.

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.