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Background: Body mass index (BMI) has been reported to be inversely associated with incident risk of non-small cell lung cancer (NSCLC). However, the underlying mechanism is still unclear. This study aimed to investigate the role of DNA methylation in the relationship between BMI and NSCLC., Methods: We carried out a genome-wide DNA methylation study of BMI in peripheral blood among 2266 Chinese participants by using Illumina Methylation arrays. For the BMI-related DNA methylation changes, their associations with NSCLC risk were further analyzed and their mediation effects on BMI-NSCLC association were also evaluated., Results: The methylation levels of four CpGs (cg12593793, cg17061862, cg11024682, and cg06500161, annotated to LMNA, ZNF143, SREBF1, and ABCG1, respectively) were found to be significantly associated with BMI. Methylation levels of cg12593793, cg11024682, and cg06500161 were observed to be inversely associated with NSCLC risk [OR (95%CI) =0.22 (0.16, 0.31), 0.39 (0.30, 0.50), and 0.66 (0.53, 0.82), respectively]. Additionally, cg11024682 in SREBF1 and cg06500161 in ABCG1 mediated 45.3% and 19.5% of the association between BMI and decreased NSCLC risk, respectively., Conclusions: In this study, we identified four DNA methylation sites associated with BMI in the Chinese populations at the genome-wide significant level. We also found that the BMI-related methylations of SREBF1 and ABCG1 could mediate about a quintile-to-half of the effect of BMI on reduced NSCLC risk, which adds a potential mechanism underlying this association., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Epidemiological studies have shown an etiological link between body mass index (BMI) and cancer risk, but evidence supporting these observations is limited. This study aimed to investigate potential associations of BMI with chromosome damage levels and lung cancer risk. First, we recruited 1333 male workers from a coke-oven plant to examine their chromosome damage levels; and then, a cohort study of 12,052 males was used to investigate the association of BMI with lung cancer incidence. We further carried out a meta-analysis for BMI and male lung cancer risk based on cohort studies. We found that men workers with excess body weight (BMI ≥ 25 kg/m(2)) had lower levels of MN frequencies than men with normal-weight (BMI: 18.5-24.9). Our cohort study indicated that, the relative risk (RR) for men with BMI ≥ 25 to develop lung cancer was 35% lower than RR for normal-weight men. Further meta-analysis showed that, compared to normal-weight men, men with BMI ≥ 25 had decreased risk of lung cancer among both the East-Asians and others populations. These results indicate that men with excess body weight had significant decreased chromosome damage levels and lower risk of lung cancer than those with normal-weight. However, further biological researches were needed to validate these associations.

Background: Observational epidemiological studies have reported the associations of high body mass index (BMI) with elevated serum uric acid (UA) level and increased risk of postmenopausal breast cancer. However, whether UA is causally induced by BMI and functioned in the BMI–breast cancer relationship remains unclear. Methods: To elucidate the causality direction between BMI and serum UA, the bidirectional Mendelian randomization (MR) analyses were performed by using summarized data from the largest Asian genome-wide association studies (GWAS) of BMI and UA carried out in over 150,000 Japanese populations. Then, a total of 19,518 postmenopausal women from the Dongfeng–Tongji (DFTJ) cohort (with a mean 8.2-year follow-up) were included and analyzed on the associations of BMI and serum UA with incidence risk of postmenopausal breast cancer by using multivariable Cox proportional hazard regression models. Mediation analysis was further conducted among DFTJ cohort to assess the intermediate role of serum UA in the BMI–breast cancer association. Results: In the bidirectional MR analyses, we observed that genetically determined BMI was causally associated with elevated serum UA [β(95% CI) = 0.225(0.111, 0.339), p < 0.001], but not vice versa. In the DFTJ cohort, each standard deviation (SD) increment in BMI (3.5 kg/m2) and UA (75.4 μmol/l) was associated with a separate 24% and 22% increased risk of postmenopausal breast cancer [HR(95% CI) = 1.24(1.07, 1.44) and 1.22(1.05, 1.42), respectively]. More importantly, serum UA could mediate 16.9% of the association between BMI and incident postmenopausal breast cancer. Conclusions: The current findings revealed a causal effect of BMI on increasing serum UA and highlighted the mediating role of UA in the BMI–breast cancer relationship. Controlling the serum level of UA among overweight postmenopausal women may help to decrease their incident risk of breast cancer. [ABSTRACT FROM AUTHOR]

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng–Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all‐cause (HR (95% CI) = 1.12 (1.10–1.14) and 1.08 (1.07–1.10), respectively) and cause‐specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1‐point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7–9 h/night) was associated with a 0.21‐year decrease in the AgingAccel (95% CI: −0.27 to −0.15) and a 0.4% decrease in the aging rate (95% CI: −0.5% to −0.3%). This study developed a machine learning–based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions. [ABSTRACT FROM AUTHOR]

Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population. The healthy lifestyle score was derived from smoking, drinking, diet, body mass index and physical activity among 23734 retired employees from the Dongfeng-Tongji Cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). The rate advancement periods (RAPs) and the population attributable risk percentage (PAR%) were estimated to indicate the benefits of removing risk lifestyle factors. During a median follow-up of 8.16 years, 2023 cancer cases were identified. Compared with 0–2 points of the healthy lifestyle score, the HRs were 0.87 (95% CI: 0.76, 0.99), 0.83 (95% CI: 0.73, 0.94), and 0.74 (95% CI: 0.64, 0.86) for 3, 4, and 5 points, respectively, with the corresponding RAPs of −4.40 (95% CI: −8.39, −0.41), −5.84 (95% CI: −9.77, −1.90), and −9.14 (95% CI: −14.03, −4.25), respectively. Approximately 15% of incident cancer cases among total population and 22% among men would be prevented by following all 5 healthy lifestyle factors. The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males. Healthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males. We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases. [ABSTRACT FROM AUTHOR]