Diet is the primary source of cadmium—a proven Group 1 human carcinogen—for non‐smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have ...produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi‐quantitative food frequency questionnaire at baseline. During a median of 22 years of follow‐up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable‐adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor‐defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06–2.22; p trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10–2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05–1.66 for each standard deviation increase in cadmium). Cadmium‐related risk of breast cancer did not vary with ER, PR or HER2 status (p‐heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer.
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Diet is the primary source of cadmium – a proven Group 1 human carcinogen – for non‐smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results, however. This first cohort study to investigate the effects of dietary cadmium on the risk of breast cancer and breast cancer subtypes defined by the expression of ER, PR, and HER2 provides further evidence that dietary cadmium increases breast cancer risk. The lack of significant heterogeneity in risk estimates between different ER and PR status neither supports nor refutes the hypothesis that cadmium acts as a metalloestrogen.
Breast cancer (BC) is the leading cause of cancer death in women. Adipokines, and other inflammation molecules linked to adiposity, are suspected to be involved in breast carcinogenesis, however ...prospective findings are inconclusive. In a prospective nested case-control study within the EPIC-Varese cohort, we used conditional logistic regression to estimate rate ratios (RRs) for BC, with 95% confidence intervals (CI), in relation to plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6, leptin, and adiponectin, controlling for BC risk factors. After a median 14.9 years, 351 BC cases were identified and matched to 351 controls. No marker was significantly associated with BC risk overall. Significant interactions between menopausal status and CRP, leptin, and adiponectin were found. Among postmenopausal women, high CRP was significantly associated with increased BC risk, and high adiponectin with significantly reduced risk. Among premenopausal women, high TNF-α was associated with significantly increased risk, and high leptin with reduced risk; interleukin-6 was associated with increased risk only in a continuous model. These findings constitute further evidence that inflammation plays a role in breast cancer. Interventions to lower CRP, TNF-α, and interleukin-6 and increase adiponectin levels may contribute to preventing BC.
Breast cancer (BC) is the most common cancer in women, with 2.3 million diagnoses in 2020. There is growing evidence that lifestyle factors, including dietary factors, particularly the complex ...interactions and synergies between different foods and nutrients (and not a single nutrient or food), may be associated with a higher risk of BC. The aim of this work was to evaluate how the Italian Mediterranean Index (IMI), the Greek Mediterranean Index, the DASH score, and the EAT-Lancet score can help lower the risk of BC, and analyze if chronic low-grade inflammation may be one of the possible mechanisms through which dietary patterns influence breast cancer risk. We evaluated the effect of adherence to these four dietary quality indices in the 9144 women of the ORDET cohort who completed a dietary questionnaire. The effect of adherence to dietary patterns on chronic inflammation biomarkers was evaluated on a subsample of 552 participants. Hazard ratios (HRs) with 95% confidence intervals (CIs) for BC risk in relation to the index score categories used were estimated using multivariable Cox models adjusted for potential confounders. Regression coefficients (β), with 95% CI for C-reactive protein (CRP), TNF-α, IL-6, leptin, and adiponectin levels in relation to adherence to dietary patterns were evaluated with the linear regression model adjusted for potential confounders. IMI was inversely associated with BC in all women (HR: 0.76, 95% CI: 0.60-0.97, P trend = 0.04), particularly among postmenopausal women (HR: 0.64, 95% CI: 0.42-0.98, P trend = 0.11). None of the other dietary patterns was associated with BC risk. Higher IMI and Greek Mediterranean Index scores were inversely associated with circulating CRP (β: -0.10, 95% CI: -0.18, -0.02, and β: -0.13, 95% CI: -0.21, -0.04). The higher score of the EAT-Lancet Index was instead associated with a higher concentration of circulating levels of CRP (β: 0.10, 95% CI: 0.02, 0.18). In conclusion, these results suggest that adherence to a typical Italian Mediterranean diet protects against BC development, especially among postmenopausal women, possibly through modulation of chronic low-grade inflammation.
Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake ...on colorectal cancer risk have been performed.
We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.
Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.
Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.
Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as ...a risk factor for breast cancer; however few studies - most confined to postmenopausal women - have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.
We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.
Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).
These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.
Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem ...to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-analysis to identify circulating microRNAs related to BC diagnosis, paying special attention to methodological problems in this research field. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seventy-five studies were included in the systematic review. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seven studies were included in the MIR21 and MIR155 meta-analysis, while four studies were included in the MIR10b metanalysis. The pooled sensitivity and specificity of MIR21 for BC diagnosis were 0.86 (95%CI 0.76-0.93) and 0.84 (95%CI 0.71-0.92), 0.83 (95%CI 0.72-0.91) and 0.90 (95%CI 0.69-0.97) for MIR155, and 0.56 (95%CI 0.32-0.71) and 0.95 (95%CI 0.88-0.98) for MIR10b, respectively. Several other microRNAs were found to be dysregulated, distinguishing BC patients from healthy controls. However, there was little consistency between included studies, making it difficult to identify specific microRNAs useful for diagnosis.
Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone ...(AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.
In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.
The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.
AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style ...(espresso and mocha) coffee consumption and CHD risk.
We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.
After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption.
Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile.
Vitamins involved in one-carbon metabolism are hypothesized to influence breast cancer (BC) risk. However, epidemiologic studies that examined associations between B vitamin intake and BC risk have ...provided inconsistent results. We prospectively examined, in the Italian ORDET cohort, whether B vitamin consumption was associated with risk of BC and BC subtypes.
After a mean follow-up of 16.5 years, 391 BCs were diagnosed among 10,786 cohort women. B vitamin intakes were estimated from food frequency questionnaires. Cox proportional hazard models adjusted for energy intake and confounders, estimated hazard ratios (HR) with 95% confidence intervals (CIs) for BC according to intake.
RRs were 0.61 (95% CI 0.38-0.97 highest vs. lowest quartile; P trend 0.025) for thiamine; 0.48 (95% CI 0.32-0.71; P trend <0.001) for riboflavin; 0.59 (95% CI 0.39-0.90; P trend 0.008) for vitamin B6, and 0.65 (95% CI 0.44-0.95; P trend 0.021) for folate. As regards risk of BC subtypes, high riboflavin and folate were significantly associated with lower risk of estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers, and high thiamine was associated with lower risk of ER-PR- cancers. High riboflavin was associated with lower risk of both HER2+ and HER2- cancers, high folate with lower risk of HER2- disease, and high thiamine with HER2+ disease.
These findings support protective effects of thiamine and one-carbon metabolism vitamins (folate, riboflavin, and vitamin B6) against BC in general; while folate may also protect against ER+PR+ and HER2- disease; and thiamine against ER-PR-, and HER2+ disease.
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