Hepatocellular Carcinoma Risk Factors and Disease Burden in a European Cohort: A Nested Case-Control Study

Trichopoulos, Dimitrios; Bamia, Christina; Λάγιου, Παγώνα; Fedirko, Veronika; Trépo, Elisabeth; Jenab, Mazda; Pischon, Tobias; Nöthlings, Ute; Overved, Kim; Tjønneland, Anne; Outzen, Malene; Clavel‐Chapelon, Françoise; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Aleksandrova, Krasimira; Benetou, Vassiliki; Zylis, Dimosthenis; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Bueno-De-Mesquita, H. Bas; Kranen, Henk J. van; Peeters, Petra H.M.; Lund, Eiliv; Quiŕos, J. Ramón; González, Carlos A.; Sánchez, María-José; Navarro, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Lindkvist, Björn; Regnér, Sara; Werner, Mårten; Hallmans, Göran; Khaw, Kay Tee; Wareham, Nick; Key, Timothy J.; Romieu, Isabelle; Chuang, Shu Chun; Murphy, Neil; Boffetta, Paolo; Trichopoulou, Antonia; Riboli, Elio

doi:10.1093/jnci/djr395

Cited by 201 publications

(178 citation statements)

References 28 publications

(24 reference statements)

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“…In the nested case-control study, participants infected with HCV/HBV, the main risk factor for HCC, were excluded. 4 The effect estimates were similar to those reported in all-cohort analyses, but the confidence intervals were wider, and the results were attenuated or lost the significance. In our cohort study, no statistically significant association between isoflavone intake and HCC risk was observed.…”

Section: Discussionsupporting

confidence: 68%

“…3 Physical activity categories were sex-specific. 4 Tertiles of total flavonoid intake (mg/day): T1,<242.6; T2, 242.6 to 472.6; T3, >472.6. To our knowledge, there is only one case-control study published from Greece evaluating the association between total flavonoid intake and HCC cancer risk, by hepatitis status.…”

Section: Discussionmentioning

confidence: 99%

“…2 Established risk factors for HCC include chronic hepatitis B and C virus (HBV/HCV) infection, heavy alcohol drinking, tobacco smoking, type 2 diabetes, obesity and aflatoxin exposure. 3,4 However, dietary factors are strongly suspected to also contribute to HCC risk. 3,5 Several epidemiological studies suggest the potential protective effect of certain food groups, such as coffee, fruits and vegetables, tea and soya products, against the development of HCC.…”

mentioning

confidence: 99%

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Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Zamora-Ros

Fedirko

Trichopoulou

et al. 2013

Intl Journal of Cancer

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Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellu- lar cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case– control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regres- sion, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR 5 0.65, 95% CI: 0.40–1.04; ptrend 5 0.065), but not with lignans. Among flavonoid subclasses, flava- nols were inversely associated with HCC risk (HR 5 0.62, 95% CI: 0.39–0.99; ptrend 5 0.06). Dietary NEAC was inversely associ- ated with HCC (FRAP: HR 0.50, 95% CI: 0.31–0.81; ptrend 5 0.001; TRAP: HR 0.49, 95% CI: 0.31–0.79; ptrend 5 0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of die- tary flavanols and antioxidants may be associated with a reduced HCC risk

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Zamora-Ros

Fedirko

Trichopoulou

et al. 2013

Intl Journal of Cancer

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“…The design has been previously described in detail, 23 and also in the Supporting Information. Briefly, 125 HCC cases with available blood samples at baseline were identified between participants' recruitment and 2006, and matched to two controls.…”

Section: Nested Case-control Subsetmentioning

confidence: 99%

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Duarte‐Salles

Fedirko

Stępień

et al. 2015

Intl Journal of Cancer

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The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case–control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65–0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55–0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68–1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88–1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73–1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk

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“…Another important objective would be to identify high-risk subpopulations of patients who would benefit the most from HCC surveillance. Some risk factors for HCC development have been identified, for example, cirrhosis etiology, diabetes, obesity and smoking [19,20], but the huge variation in reported HCC risk estimates opens the possibility that there are other important risk factors, including environmental and genetic ones. Comparing cohorts from institutions with different surveillance strategies may further improve our understanding of the impact of surveillance, even though they cannot substitute the much-needed randomized trials.…”

mentioning

confidence: 99%

Hepatocellular carcinoma surveillance in patients with alcoholic cirrhosis

Jepsen

Ott

2012

Expert Review of Gastroenterology & Hepatology

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Hepatocellular Carcinoma Risk Factors and Disease Burden in a European Cohort: A Nested Case-Control Study

Cited by 201 publications

References 28 publications

Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Hepatocellular carcinoma surveillance in patients with alcoholic cirrhosis

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