ImportanceGenetic and lifestyle factors are related to thyroid cancer (TC). Whether a healthy lifestyle is associated with TC and could attenuate the influence of genetic variants in TC remains equivocal.ObjectivesTo examine the associations between genetics and healthy lifestyle with incident TC and whether adherence to a healthy lifestyle modifies the association between genetic variants and TC.Design, Setting, and ParticipantsA prospective cohort study using UK Biobank data recruited 502 505 participants aged 40 to 69 years between March 13, 2006, and October 1, 2010. A total of 307 803 participants of European descent were recruited at baseline, and 264 956 participants were available for the present study. Data analysis was conducted from November 1, 2021, to April 22, 2022.ExposuresLifestyle behaviors were determined by diet index, physical activity, weight, smoking, and alcohol consumption. Lifestyle was categorized as unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5). The polygenic risk score (PRS) was derived from a meta–genome-wide association study using 3 cohorts and categorized as low, intermediate, and high.Main Outcomes and MeasuresThyroid cancer was defined using the International Classification of Diseases, Ninth Revision (code 193), International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (code C73), and self-report (code 1065).ResultsOf 264 956 participants, 137 665 were women (52%). The median age was 57 (IQR, 49-62) years. During a median follow-up of 11.1 (IQR, 10.33-11.75) years (2 885 046 person-years), 423 incident TCs were ascertained (14.66 per 100 000 person-years). Higher PRSs were associated with TC (hazard ratio [HR], 2.25; 95% CI, 1.91-2.64; P = 8.65 × 10−23). An unfavorable lifestyle was also associated with a higher risk of TC (HR, 1.93; 95% CI, 1.50-2.49; P < .001). When stratified by PRS, unfavorable lifestyle was associated with TC in the higher PRS group (favorable vs unfavorable HR, 0.52; 95% CI, 0.37-0.73; P < .001). Furthermore, participants with both a high PRS and unfavorable lifestyle had the highest risk of TC (HR, 4.89; 95% CI, 3.03-7.91; P < .001).Conclusions and RelevanceIn this prospective cohort study, genetic and lifestyle factors were independently associated with incident TC, which suggests that a healthier lifestyle may attenuate the deleterious influence of genetics on the risk of TC in individuals of European descent.
The majority of epidemiological investigations on metal exposures and lipid metabolism employed cross-sectional designs and focused on individual metal. We explored the associations between metal mixture exposures and longitudinal changes in lipid profiles and potential sexual heterogeneity. We recruited 250 men and 73 women, aged 40 years at baseline (2012), and followed them up in 2020, from the manganese-exposed workers healthy cohort. We detected metal concentrations of blood cells at baseline with inductively coupled plasma mass spectrometry. Lipid profiles were repeatedly measured over 8 years of follow-up. We performed sparse partial least squares (sPLS) model to evaluate multi-pollutant associations. Bayesian kernel machine regression was utilized for metal mixtures as well as evaluating their joint impacts on lipid changes. In sPLS models, positive association was found between manganese and change in total cholesterol (TC) (beta = 0.169), while negative association was observed between cobalt (beta = -0.134) and change in low density lipoprotein cholesterol (LDL-C) (beta = -0.178) among overall participants, which were consistent in men. Furthermore, manganese was associated with increased risks of incident hyper-cholesterolemia or hyper-LDL cholesterolemia (odds ratio: 1.849 or 2.354). Interestingly, rubidium was positively associated with change in LDL-C (beta = 0.273) in women, while copper was negatively associated with change in TC (beta = -0.359) and LDL-C (beta = -0.267). Magnesium was negatively associated with change in TC (beta = -0.327). We did not observe the significantly cumulative effect of metal mixtures with lipid changes. In comparison to other metals, manganese had a more significant influence in lipid changes (posterior inclusion probability = 0.559 for TC in men). Furthermore, male rats exposed to manganese (20mg/kg) had higher level of LDL-C in plasma and more apparent inflammatory infiltration, vacuolation of liver cells, nuclear pyknosis, fatty change than the controls. These findings highlight the potential role of metal mixtures in lipid metabolism with sex-dependent heterogeneity. More researches are needed to explore the underlying mechanisms.
Phthalates have been shown to have adverse effects on neurodevelopment, which may be gender-specific. However, the association between prenatal mixed exposure to phthalates and children's neurodevelopment remain limited. We measured prenatal phthalate levels and children's neurodevelopment. Logistic regression was fitted to examine the association. Among boys, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) has adverse effects on gross motor (OR: 7.39, 95% CI:1.42, 38.5). For gross motor in boys, joint effect was discovered between mono-2-ethylhexyl phthalate (MEHP) and MEHHP. Moreover, synergistic effects were found for MEHP with vanadium and cadmium, and antagonistic effects for MEHP with magnesium, calcium, titanium, iron, copper, selenium, rubidium and strontium. We did not find statistically significant relationships in girls. In the 1st trimester, adverse effects were identified between mono-2-ethyl-5-oxoyhexyl phthalate (MEOHP) and adaptation ( P = 0.024), and monomethyl phthalate (MMP) with social area ( P = 0.016). In the 2nd trimester, the risk of social development increased with MEHHP. In summary, we found boys may be more vulnerable to the neurotoxicity than girls in gross motor, and the 1st and 2nd trimester might be more sensitive in terms of phthalates on children. To some extent, supplementation of the appropriate metals in the 1st trimester may reduce or inhibit the absorption of phthalates by the foetus, especially in males, so as to prevent neurodevelopmental impairment.
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