Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, ...sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow‐up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri‐menopausal women, 111 in post‐menopausal women, and 70 in men) and 706 cancer‐free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre‐menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, ptrend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post‐menopausal women and men but may suggest an involvement of altered sex steroid production in pre‐menopausal women.
What's new?
Thyroid cancer occurs more often in women than men, suggesting that sex hormones may contribute to the disease. Here, the authors investigated the association between circulating sex steroid hormones, sex hormone binding globulin protein (SHBG), and the risk of thyroid cancer in both men and women using data from the European Prospective Investigation into Cancer and nutrition (EPIC). They measured concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre‐menopausal women only), as well as SHBG. Overall, they did not detect a strong association between hormones, SHBG and thyroid cancer incidence.
Abbreviations AGEs advanced glycation endproducts BMI body mass index CEL N-epsilon-(1-carboxyethyl)-lysine CI confidence intervals CML N-epsilon-(carboxymethyl)-lysine DQ dietary questionnaires EPIC ...European Prospective Investigation into Cancer and Nutrition HR hazard ratios MG-H1 N-delta-5-hydro-5-methyl-4-imidazolon-2-yl-ornithine RAGE receptor of AGEs SD standard deviation sRAGE soluble receptor of AGEs UPLC-MS/MS ultra-performance liquid chromatography-tandem mass spectrometry Dear Editor, In the European region, which shares 22.8% of the global cancer burden for 10% of the global population, there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020 1. Previous clinical and experimental studies suggested that AGEs are proinflammatory, increase oxidative stress and activate pro-carcinogenic transcription factors such as NFκB and STAT3 as well as cell signaling pathways like mitogen-activated protein kinase (MAPK) by binding on the receptor for AGEs (RAGE) 7. ...there always remains the possibility of unmeasured confounding. ...in this large multinational prospective cohort study across 20 anatomical cancer sites, a higher intake of dietary AGEs was not associated with an increased risk of overall cancer and most cancer types studied.
Collection of reliable and comparable individual food consumption data is of primary importance to better understand, control and monitor malnutrition and its related comorbidities in low- and ...middle-income countries (LMICs), including in Africa. The lack of standardised dietary tools and their related research support infrastructure remains a major obstacle to implement concerted and region-specific research and action plans worldwide. Citing the magnitude and importance of this challenge, the International Agency for Research on Cancer (IARC/WHO) launched the "Global Nutrition Surveillance initiative" to pilot test the use of a standardized 24-h dietary recall research tool (GloboDiet), validated in Europe, in other regions. In this regard, the development of the GloboDiet-Africa can be optimised by better understanding of the local specific methodological needs, barriers and opportunities. The study aimed to evaluate the standardized 24-h dietary recall research tool (GloboDiet) as a possible common methodology for research and surveillance across Africa.
A consultative panel of African and international experts in dietary assessment participated in six e-workshop sessions. They completed an in-depth e-questionnaire to evaluate the GloboDiet dietary methodology before and after participating in the e-workshop.
The 29 experts expressed their satisfaction on the potential of the software to address local specific needs when evaluating the main structure of the software, the stepwise approach for data collection and standardisation concept. Nevertheless, additional information to better describe local foods and recipes, as well as particular culinary patterns (e.g. mortar pounding), were proposed. Furthermore, food quantification in shared-plates and -bowls eating situations and interviewing of populations with low literacy skills, especially in rural settings, were acknowledged as requiring further specific considerations and appropriate solutions.
An overall positive evaluation of the GloboDiet methodology by both African and international experts, supports the flexibility and potential applicability of this tool in diverse African settings and sets a positive platform for improved dietary monitoring and surveillance. Following this evaluation, prerequisite for future implementation and/or adaptation of GloboDiet in Africa, rigorous and robust capacity building as well as knowledge transfer will be required to roadmap a stepwise approach to implement this methodology across pilot African countries/regions.
There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, ...dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.
Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; P
= .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; P
= .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; P
= .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; P
= .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; P
< .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (P
= .026).
In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma ...levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial‐processed trans (iTFA), and ruminant‐sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow‐up = 15 years). In a nested case‐control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable‐adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69‐0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74‐0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70‐0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32‐0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00‐2.64). Dietary total MUFA was inversely associated with colon cancer (per 1‐SD increment, HR1‐SD = 0.92, 95%CI: 0.85‐0.98), but not rectal cancer (HR1‐SD = 1.04, 95%CI:0.95‐1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1‐SD = 1.07, 95%CI:1.02‐1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
What's new?
The role of specific fatty acids in cancer development is not fully understood. In this large, prospective European study of colorectal cancer (CRC) risk, the authors found that dietary myristic and palmitic acids from dairy were inversely associated with CRC risk, as were total saturated (SFA) and monounsaturated (MUFA) fatty acids. Dietary industrially‐processed trans fatty acids (iTFA) were positively associated with rectal cancer. These results suggest that total and individual saturated fatty acids may be relevant to the aetiology of CRC.
Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components ...with colorectal cancer (CRC) development is inconclusive.
We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.
Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HR
:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HR
:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HR
:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HR
:1.11, 95%CI:0.94, 1.31), heme (HR
:0.95; 95%CI:0.84, 1.07) or non-heme iron (HR
:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).
Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
Glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs) could contribute to colorectal cancer development and progression due to their pro‐oxidative and pro‐inflammatory properties. ...However, the association of glycer‐AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer‐AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer‐AGEs concentrations with CRC‐specific and all‐cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow‐up, 529 participants died (409 from CRC). Glycer‐AGEs were statistically significantly positively associated with CRC‐specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04‐2.25, Ptrend = .002) and all‐cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16‐2.26, Ptrend < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer‐AGEs and CRC‐specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74‐1.42; HRdistal colon = 1.51, 95% CI: 1.20‐1.91; Peffect modification = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer‐AGEs category relative to lowest BMI and glycer‐AGEs category for both CRC‐specific (HR = 1.78, 95% CI: 1.02‐3.01) and all‐cause mortality (HR = 2.15, 95% CI: 1.33‐3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer‐AGEs are positively associated with CRC‐specific and all‐cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
What's new?
Eating foods high in sugar has been associated with risk of colorectal cancer (CRC). As the body processes dietary sugars, it generates compounds called glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs). Here, the authors investigated the relationship between glycer‐AGEs and CRC mortality. In an analysis of 1034 CRC cases from the EPIC cohort, they found that prediagnostic circulating glycer‐AGEs were associated with both CRC‐specific and all‐cause mortality.
Traditional body-shape indices such as Waist Circumference (WC), Hip Circumference (HC), and Waist-to-Hip Ratio (WHR) are associated with colorectal cancer (CRC) risk, but are correlated with Body ...Mass Index (BMI), and adjustment for BMI introduces a strong correlation with height. Thus, new allometric indices have been developed, namely A Body Shape Index (ABSI), Hip Index (HI), and Waist-to-Hip Index (WHI), which are uncorrelated with weight and height; these have also been associated with CRC risk in observational studies, but information from Mendelian randomization (MR) studies is missing.
We used two-sample MR to examine potential causal cancer site- and sex-specific associations of the genetically-predicted allometric body-shape indices with CRC risk, and compared them with BMI-adjusted traditional body-shape indices, and BMI. Data were obtained from UK Biobank and the GIANT consortium, and from GECCO, CORECT and CCFR consortia.
WHI was positively associated with CRC in men (OR per SD: 1.20, 95% CI: 1.03-1.39) and in women (1.15, 1.06-1.24), and similarly for colon and rectal cancer. ABSI was positively associated with colon and rectal cancer in men (1.27, 1.03-1.57; and 1.40, 1.10-1.77, respectively), and with colon cancer in women (1.20, 1.07-1.35). There was little evidence for association between HI and colon or rectal cancer. The BMI-adjusted WHR and HC showed similar associations to WHI and HI, whereas WC showed similar associations to ABSI only in women.
This large MR study provides strong evidence for a potential causal positive association of the allometric indices ABSI and WHI with CRC in both sexes, thus establishing the association between abdominal fat and CRC without the limitations of the traditional waist size indices and independently of BMI. Among the BMI-adjusted traditional indices, WHR and HC provided equivalent associations with WHI and HI, while differences were observed between WC and ABSI.
Purpose
Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and ...its determinants in healthy European adults.
Methods
Sociodemographic, lifestyle, iron status, dietary information, and
HFE
genotyping were obtained from controls from the nested case–control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants.
Results
Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of
HFE
C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight.
Conclusion
Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.
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