Dietary Mn intake may have a beneficial effect in reducing cancer risk; however, its association with thyroid cancer (TC) risk remains inadequately understood. Additionally, Mn was associated with inflammation markers. Thus, we examined whether dietary Mn intake emerges a protective role against TC and whether this preventative effect has an interaction with IL1 receptor type 1 (IL1R1) rs3917225. The prospective study was designed at National Cancer Center in Korea between October 2007 and December 2020 including 17 754 participants. We identified TC cases by following participants until December 2020. Mn intake was collected using a semiquantitative food frequency questionnaire (SQFFQ). Genotyping was performed to determine IL1R1 rs3917225. The hazard ratios (HR) and 95 % confidence interval (CI) were calculated with a Cox proportional hazards model. We ascertained 108 incident TC cases throughout follow-up duration. Dietary Mn intake was found to be inversely associated with TC risk (HR (95 % CI)=0·64 (0·44, 0·95)). However, IL1R1 rs3917225 seemed to modify this association; the protective effect was limited to G-allele carriers (HR = 0·30 (0·11, 0·86), P interaction=0·028). A higher dietary Mn was suggested to be a protective factor against TC. Additionally, we drew a potential biological interaction between Mn intake and IL1R1 rs3917225 with a greater effect among individuals with a minor allele. This implies that when considering the cancer-preventive role of Mn, it is important to account for the influence of inflammatory gene participation.

The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose–response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540 184 individuals and 25 670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-interaction ≤ 0·02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.