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  1. McKenzie F, Biessy C, Ferrari P, Freisling H, Rinaldi S, Chajès V, et al.
    Medicine (Baltimore), 2016 Apr;95(16):e2850.
    PMID: 27100409 DOI: 10.1097/MD.0000000000002850
    It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors.This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models.There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41% and 33% for alcohol-related, 49% and 46% for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers.Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men.
  2. Chajès V, Assi N, Biessy C, Ferrari P, Rinaldi S, Slimani N, et al.
    Ann Oncol, 2017 Nov 01;28(11):2836-2842.
    PMID: 28950350 DOI: 10.1093/annonc/mdx482
    BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.

    MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.

    RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.

    CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

  3. Matejcic M, de Batlle J, Ricci C, Biessy C, Perrier F, Huybrechts I, et al.
    Int J Cancer, 2017 Mar 15;140(6):1246-1259.
    PMID: 27905104 DOI: 10.1002/ijc.30536
    Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
  4. Matejcic M, Lesueur F, Biessy C, Renault AL, Mebirouk N, Yammine S, et al.
    Int J Cancer, 2018 Nov 15;143(10):2437-2448.
    PMID: 30110135 DOI: 10.1002/ijc.31797
    There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.
  5. Chajès V, Biessy C, Ferrari P, Romieu I, Freisling H, Huybrechts I, et al.
    PLoS One, 2015;10(2):e0118206.
    PMID: 25675445 DOI: 10.1371/journal.pone.0118206
    BACKGROUND: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region.

    RESULTS: In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend

  6. Freisling H, Noh H, Slimani N, Chajès V, May AM, Peeters PH, et al.
    Eur J Nutr, 2018 Oct;57(7):2399-2408.
    PMID: 28733927 DOI: 10.1007/s00394-017-1513-0
    PURPOSE: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years.

    METHODS: This study includes 373,293 men and women, 25-70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI).

    RESULTS: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (-0.07 kg; 95% CI -0.12 to -0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92-0.98) or obese (RR 0.95; 95% CI 0.90-0.99) (both P trend <0.008).

    CONCLUSIONS: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.

  7. Romieu I, Ferrari P, Chajès V, de Batlle J, Biessy C, Scoccianti C, et al.
    Int J Cancer, 2017 Jan 15;140(2):316-321.
    PMID: 27599758 DOI: 10.1002/ijc.30415
    Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person-years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (<18.5 g/day), the risk of BC per 10 g/day of alcohol intake was 1.06 (1.03-1.08) while among subjects with high intake of fiber (>24.2 g/day) the risk of BC was 1.02 (0.99-1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber-rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (<18.5 g/day) had the highest risk for BC. Specific benefits were associated with fibers from vegetable, warranting further investigations into specific fiber sources and their mechanistic interactions with alcohol-induced BC risk.
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