• CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation.

      Honda, K; Katzke, V A; Hüsing, A; Okaya, S; Shoji, H; Onidani, K; Olsen, A; Tjønneland, A; Overvad, K; Weiderpass, E; Vineis, P; Muller, D; Tsilidis, K K; Palli, D; Pala, V; Tumino, R; Naccarati, A; Panico, S; Aleksandrova, K; Boeing, H; Bueno-de-Mesquita, H B; Peeters, P H; Trichopoulou, A; Lagiou, P; Khaw, K-T; Wareham, N J; Travis, R C; Merino, S; Duell, E J; Rodríguez-Barranco, M; Chirlaque, M D; Barricarte, A; Rebours, V; Boutron-Ruault, M-C; Romana Mancini, F; Brennan, P; Scelo, G; Manjer, J; Sund, M; Öhlund, D; Canzian, F; Kaaks, R (2018-09-27)
      Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. This article is protected by copyright. All rights reserved.
    • DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.

      Matullo, G; Dunning, A M; Guarrera, S; Baynes, C; Polidoro, S; Garte, S; Autrup, H; Malaveille, C; Peluso, M; Airoldi, L; Veglia, F; Gormally, E; Hoek, G; Krzyzanowski, M; Overvad, K; Raaschou-Nielsen, O; Clavel-Chapelon, F; Linseisen, J; Boeing, H; Trichopoulou, A; Palli, D; Krogh, V; Tumino, R; Panico, S; Bueno-De-Mesquita, H Bas; Peeters, Petra H M; Lund, E; Pera, G; Martinez, C; Dorronsoro, M; Barricarte, A; Tormo, M J; Quiros, J R; Day, N E; Key, T J; Saracci, R; Kaaks, R; Riboli, E; Vineis, P (2006-05-01)
      Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.
    • A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

      Chajès, V; Assi, N; Biessy, C; Ferrari, P; Rinaldi, S; Slimani, N; Lenoir, G M; Baglietto, L; His, M; Boutron-Ruault, M C; Trichopoulou, A; Lagiou, P; Katsoulis, M; Kaaks, R; Kühn, T; Panico, S; Pala, V; Masala, G; Bueno-de-Mesquita, H B; Peeters, P H; van Gils, C; Hjartåker, A; Standahl Olsen, K; Borgund Barnung, R; Barricarte, A; Redondo-Sanchez, D; Menéndez, V; Amiano, P; Wennberg, M; Key, T; Khaw, K T; Merritt, M A; Riboli, E; Gunter, M J; Romieu, I (2017-11-01)
      Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.