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1. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: A multinational cohort study

Author

Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, A, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuhn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, C, Menendez, V, Agudo, A, Sanchez, M, Amiano, P, Santiuste, C, Gurrea, A, Tong, T, Schmidt, J, Tzoulaki, I, Tsilidis, K, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, H, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, N, Gunter, M, Ferrari, P, Freisling H., Viallon V., Lennon H., Bagnardi V., Ricci C., Butterworth A. S., Sweeting M., Muller D., Romieu I., Bazelle P., Kvaskoff M., Arveux P., Severi G., Bamia C., Kuhn T., Kaaks R., Bergmann M., Boeing H., Tjonneland A., Olsen A., Overvad K., Dahm C. C., Menendez V., Agudo A., Sanchez M. -J., Amiano P., Santiuste C., Gurrea A. B., Tong T. Y. N., Schmidt J. A., Tzoulaki I., Tsilidis K. K., Ward H., Palli D., Agnoli C., Tumino R., Ricceri F., Panico S., Picavet H. S. J., Bakker M., Monninkhof E., Nilsson P., Manjer J., Rolandsson O., Thysell E., Weiderpass E., Jenab M., Riboli E., Vineis P., Danesh J., Wareham N. J., Gunter M. J., Ferrari P., Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, A, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuhn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, C, Menendez, V, Agudo, A, Sanchez, M, Amiano, P, Santiuste, C, Gurrea, A, Tong, T, Schmidt, J, Tzoulaki, I, Tsilidis, K, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, H, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, N, Gunter, M, Ferrari, P, Freisling H., Viallon V., Lennon H., Bagnardi V., Ricci C., Butterworth A. S., Sweeting M., Muller D., Romieu I., Bazelle P., Kvaskoff M., Arveux P., Severi G., Bamia C., Kuhn T., Kaaks R., Bergmann M., Boeing H., Tjonneland A., Olsen A., Overvad K., Dahm C. C., Menendez V., Agudo A., Sanchez M. -J., Amiano P., Santiuste C., Gurrea A. B., Tong T. Y. N., Schmidt J. A., Tzoulaki I., Tsilidis K. K., Ward H., Palli D., Agnoli C., Tumino R., Ricceri F., Panico S., Picavet H. S. J., Bakker M., Monninkhof E., Nilsson P., Manjer J., Rolandsson O., Thysell E., Weiderpass E., Jenab M., Riboli E., Vineis P., Danesh J., Wareham N. J., Gunter M. J., and Ferrari P.

Abstract

Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and

Published
2020

2. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author

DeVries, A.A.F., Dennis, J., Tyrer, J.P., Peng, P.C., Coetzee, S.G., Reyes, A.L., Plummer, J.T., Davis, B.D., Chen, S.S., Dezem, F.S., Aben, K.K.H., Anton-Culver, H., Antonenkova, N.N., Beckmann, M.W., Beeghly-Fadiel, A., Berchuck, A., Bogdanova, N.V., Bogdanova-Markov, N., Brenton, J.D., Butzow, R., Campbell, I., Chang-Claude, J., Chenevix-Trench, G., Cook, L.S., Defazio, A., Doherty, J.A., Dörk, T., Eccles, D.M., Eliassen, A.H., Fasching, P.A., Fortner, R.T., Giles, G.G., Goode, E.L., Goodman, M.T., Gronwald, J., Håkansson, N., Hildebrandt, M.A., Huff, C., Huntsman, D.G., Jensen, A., Kar, S., Karlan, B.Y., Khusnutdinova, E.K., Kiemeney, L.A.L.M., Kjaer, S.K., Kupryjanczyk, J., Labrie, M., Lambrechts, D., Le, N.D., Lubiński, J., May, T., Menon, U., Milne, R.L., Modugno, F., Monteiro, Ana, Moysich, K.B., Odunsi, K., Olsson, H., Pearce, C.L., Pejovic, T., Ramus, S.J., Riboli, E., Riggan, M.J., Romieu, I., Sandler, D.P., Schildkraut, J.M., Setiawan, V.W., Sieh, W., Song, H., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Tworoger, S.S., Nieuwenhuysen, E. Van, Edwards, D.V., Webb, P.M., Wentzensen, N., Whittemore, A.S., Wolk, A., Wu, A.H., Ziogas, Argyrios, Freedman, M.L., Lawrenson, K., Pharoah, P.D., Easton, D.F., Gayther, S.A., Jones, M.R., DeVries, A.A.F., Dennis, J., Tyrer, J.P., Peng, P.C., Coetzee, S.G., Reyes, A.L., Plummer, J.T., Davis, B.D., Chen, S.S., Dezem, F.S., Aben, K.K.H., Anton-Culver, H., Antonenkova, N.N., Beckmann, M.W., Beeghly-Fadiel, A., Berchuck, A., Bogdanova, N.V., Bogdanova-Markov, N., Brenton, J.D., Butzow, R., Campbell, I., Chang-Claude, J., Chenevix-Trench, G., Cook, L.S., Defazio, A., Doherty, J.A., Dörk, T., Eccles, D.M., Eliassen, A.H., Fasching, P.A., Fortner, R.T., Giles, G.G., Goode, E.L., Goodman, M.T., Gronwald, J., Håkansson, N., Hildebrandt, M.A., Huff, C., Huntsman, D.G., Jensen, A., Kar, S., Karlan, B.Y., Khusnutdinova, E.K., Kiemeney, L.A.L.M., Kjaer, S.K., Kupryjanczyk, J., Labrie, M., Lambrechts, D., Le, N.D., Lubiński, J., May, T., Menon, U., Milne, R.L., Modugno, F., Monteiro, Ana, Moysich, K.B., Odunsi, K., Olsson, H., Pearce, C.L., Pejovic, T., Ramus, S.J., Riboli, E., Riggan, M.J., Romieu, I., Sandler, D.P., Schildkraut, J.M., Setiawan, V.W., Sieh, W., Song, H., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Tworoger, S.S., Nieuwenhuysen, E. Van, Edwards, D.V., Webb, P.M., Wentzensen, N., Whittemore, A.S., Wolk, A., Wu, A.H., Ziogas, Argyrios, Freedman, M.L., Lawrenson, K., Pharoah, P.D., Easton, D.F., Gayther, S.A., and Jones, M.R.

Abstract

Item does not contain fulltext, BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. RESULTS: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CONCLUSIONS: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Published
2022

3. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author

DeVries, A.A.F., Dennis, J., Tyrer, J.P., Peng, P.C., Coetzee, S.G., Reyes, A.L., Plummer, J.T., Davis, B.D., Chen, S.S., Dezem, F.S., Aben, K.K.H., Anton-Culver, H., Antonenkova, N.N., Beckmann, M.W., Beeghly-Fadiel, A., Berchuck, A., Bogdanova, N.V., Bogdanova-Markov, N., Brenton, J.D., Butzow, R., Campbell, I., Chang-Claude, J., Chenevix-Trench, G., Cook, L.S., Defazio, A., Doherty, J.A., Dörk, T., Eccles, D.M., Eliassen, A.H., Fasching, P.A., Fortner, R.T., Giles, G.G., Goode, E.L., Goodman, M.T., Gronwald, J., Håkansson, N., Hildebrandt, M.A., Huff, C., Huntsman, D.G., Jensen, A., Kar, S., Karlan, B.Y., Khusnutdinova, E.K., Kiemeney, L.A.L.M., Kjaer, S.K., Kupryjanczyk, J., Labrie, M., Lambrechts, D., Le, N.D., Lubiński, J., May, T., Menon, U., Milne, R.L., Modugno, F., Monteiro, Ana, Moysich, K.B., Odunsi, K., Olsson, H., Pearce, C.L., Pejovic, T., Ramus, S.J., Riboli, E., Riggan, M.J., Romieu, I., Sandler, D.P., Schildkraut, J.M., Setiawan, V.W., Sieh, W., Song, H., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Tworoger, S.S., Nieuwenhuysen, E. Van, Edwards, D.V., Webb, P.M., Wentzensen, N., Whittemore, A.S., Wolk, A., Wu, A.H., Ziogas, Argyrios, Freedman, M.L., Lawrenson, K., Pharoah, P.D., Easton, D.F., Gayther, S.A., Jones, M.R., DeVries, A.A.F., Dennis, J., Tyrer, J.P., Peng, P.C., Coetzee, S.G., Reyes, A.L., Plummer, J.T., Davis, B.D., Chen, S.S., Dezem, F.S., Aben, K.K.H., Anton-Culver, H., Antonenkova, N.N., Beckmann, M.W., Beeghly-Fadiel, A., Berchuck, A., Bogdanova, N.V., Bogdanova-Markov, N., Brenton, J.D., Butzow, R., Campbell, I., Chang-Claude, J., Chenevix-Trench, G., Cook, L.S., Defazio, A., Doherty, J.A., Dörk, T., Eccles, D.M., Eliassen, A.H., Fasching, P.A., Fortner, R.T., Giles, G.G., Goode, E.L., Goodman, M.T., Gronwald, J., Håkansson, N., Hildebrandt, M.A., Huff, C., Huntsman, D.G., Jensen, A., Kar, S., Karlan, B.Y., Khusnutdinova, E.K., Kiemeney, L.A.L.M., Kjaer, S.K., Kupryjanczyk, J., Labrie, M., Lambrechts, D., Le, N.D., Lubiński, J., May, T., Menon, U., Milne, R.L., Modugno, F., Monteiro, Ana, Moysich, K.B., Odunsi, K., Olsson, H., Pearce, C.L., Pejovic, T., Ramus, S.J., Riboli, E., Riggan, M.J., Romieu, I., Sandler, D.P., Schildkraut, J.M., Setiawan, V.W., Sieh, W., Song, H., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Tworoger, S.S., Nieuwenhuysen, E. Van, Edwards, D.V., Webb, P.M., Wentzensen, N., Whittemore, A.S., Wolk, A., Wu, A.H., Ziogas, Argyrios, Freedman, M.L., Lawrenson, K., Pharoah, P.D., Easton, D.F., Gayther, S.A., and Jones, M.R.

Abstract

Contains fulltext : 287571.pdf (Publisher’s version ) (Open Access), BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. RESULTS: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CONCLUSIONS: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Published
2022

4. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author

DeVries, AA, Dennis, J, Tyrer, JP, Peng, P-C, Coetzee, SG, Reyes, AL, Plummer, JT, Davis, BD, Chen, SS, Dezem, FS, Aben, KKH, Anton-Culver, H, Antonenkova, NN, Beckmann, MW, Beeghly-Fadiel, A, Berchuck, A, Bogdanova, N, Bogdanova-Markov, N, Brenton, JD, Butzow, R, Campbell, I, Chang-Claude, J, Chenevix-Trench, G, Cook, LS, DeFazio, A, Doherty, JA, Dork, T, Eccles, DM, Eliassen, AH, Fasching, PA, Fortner, RT, Giles, GG, Goode, EL, Goodman, MT, Gronwald, J, Hakansson, N, Hildebrandt, MAT, Huff, C, Huntsman, DG, Jensen, A, Kar, S, Karlan, BY, Khusnutdinova, EK, Kiemeney, LA, Kjaer, SK, Kupryjanczyk, J, Labrie, M, Lambrechts, D, Le, ND, Lubinski, J, May, T, Menon, U, Milne, RL, Modugno, F, Monteiro, AN, Moysich, KB, Odunsi, K, Olsson, H, Pearce, CL, Pejovic, T, Ramus, SJ, Riboli, E, Riggan, MJ, Romieu, I, Sandler, DP, Schildkraut, JM, Setiawan, VW, Sieh, W, Song, H, Sutphen, R, Terry, KL, Thompson, PJ, Titus, L, Tworoger, SS, Van Nieuwenhuysen, E, Edwards, DV, Webb, PM, Wentzensen, N, Whittemore, AS, Wolk, A, Wu, AH, Ziogas, A, Freedman, ML, Lawrenson, K, Pharoah, PDP, Easton, DF, Gayther, SA, Jones, MR, DeVries, AA, Dennis, J, Tyrer, JP, Peng, P-C, Coetzee, SG, Reyes, AL, Plummer, JT, Davis, BD, Chen, SS, Dezem, FS, Aben, KKH, Anton-Culver, H, Antonenkova, NN, Beckmann, MW, Beeghly-Fadiel, A, Berchuck, A, Bogdanova, N, Bogdanova-Markov, N, Brenton, JD, Butzow, R, Campbell, I, Chang-Claude, J, Chenevix-Trench, G, Cook, LS, DeFazio, A, Doherty, JA, Dork, T, Eccles, DM, Eliassen, AH, Fasching, PA, Fortner, RT, Giles, GG, Goode, EL, Goodman, MT, Gronwald, J, Hakansson, N, Hildebrandt, MAT, Huff, C, Huntsman, DG, Jensen, A, Kar, S, Karlan, BY, Khusnutdinova, EK, Kiemeney, LA, Kjaer, SK, Kupryjanczyk, J, Labrie, M, Lambrechts, D, Le, ND, Lubinski, J, May, T, Menon, U, Milne, RL, Modugno, F, Monteiro, AN, Moysich, KB, Odunsi, K, Olsson, H, Pearce, CL, Pejovic, T, Ramus, SJ, Riboli, E, Riggan, MJ, Romieu, I, Sandler, DP, Schildkraut, JM, Setiawan, VW, Sieh, W, Song, H, Sutphen, R, Terry, KL, Thompson, PJ, Titus, L, Tworoger, SS, Van Nieuwenhuysen, E, Edwards, DV, Webb, PM, Wentzensen, N, Whittemore, AS, Wolk, A, Wu, AH, Ziogas, A, Freedman, ML, Lawrenson, K, Pharoah, PDP, Easton, DF, Gayther, SA, and Jones, MR

Abstract

BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. RESULTS: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CONCLUSIONS: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Published
2022

5. Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies

Author

Dugue, P-A, Bodelon, C, Chung, FF, Brewer, HR, Ambatipudi, S, Sampson, JN, Cuenin, C, Chajes, V, Romieu, I, Fiorito, G, Sacerdote, C, Krogh, V, Panico, S, Tumino, R, Vineis, P, Polidoro, S, Baglietto, L, English, D, Severi, G, Giles, GG, Milne, RL, Herceg, Z, Garcia-Closas, M, Flanagan, JM, Southey, MC, Dugue, P-A, Bodelon, C, Chung, FF, Brewer, HR, Ambatipudi, S, Sampson, JN, Cuenin, C, Chajes, V, Romieu, I, Fiorito, G, Sacerdote, C, Krogh, V, Panico, S, Tumino, R, Vineis, P, Polidoro, S, Baglietto, L, English, D, Severi, G, Giles, GG, Milne, RL, Herceg, Z, Garcia-Closas, M, Flanagan, JM, and Southey, MC

Abstract

BACKGROUND: DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. METHODS: Using data from four prospective case-control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. RESULTS: None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath 'age acceleration' (AA): OR per SD = 1.02, 95%CI: 0.95-1.10; AA-Hannum: OR = 1.03, 95%CI:0.95-1.12; PhenoAge: OR = 1.01, 95%CI: 0.94-1.09 and GrimAge: OR = 1.03, 95%CI: 0.94-1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01-1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. CONCLUSION

Published
2022

6. Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Author

Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., Romieu, I., Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., and Romieu, I.

Abstract

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity. Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis. Results: A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity. Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Published
2021

7. Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., Romieu, I., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., and Romieu, I.

Published
2021

8. Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., Romieu, I., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., and Romieu, I.

Published
2021

9. Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., Romieu, I., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Algemeen Theoretical Physics, Amadou, A., Freisling, H., Jenab, M., Tsilidis, K.K., Trichopoulou, A., Boffetta, P., Van Guelpen, B., Mokoroa, O., Wilsgaard, T., Kee, F., Schöttker, B., Ordóñez-Mena, J.M., Männistö, S., Söderberg, S., Vermeulen, R.C.H., Quirós, J.R., Liao, L.M., Sinha, R., Kuulasmaa, K., Brenner, H., and Romieu, I.

Published
2021

10. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

Author

Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, AS, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuehn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, CC, Menendez, V, Agudo, A, Sanchez, M-J, Amiano, P, Santiuste, C, Gurrea, AB, Tong, TYN, Schmidt, JA, Tzoulaki, I, Tsilidis, KK, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, HSJ, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, NJ, Gunter, MJ, Ferrari, P, Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, AS, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuehn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, CC, Menendez, V, Agudo, A, Sanchez, M-J, Amiano, P, Santiuste, C, Gurrea, AB, Tong, TYN, Schmidt, JA, Tzoulaki, I, Tsilidis, KK, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, HSJ, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, NJ, Gunter, MJ, and Ferrari, P

Abstract

BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and

Published
2020

11. Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Author

Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., Jenab, M., Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., and Jenab, M.

Abstract

Contains fulltext : 215343.pdf (publisher's version ) (Open Access), Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGFbeta) signaling was associated with CRC risk (P

Published
2019

12. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.

Author

Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., Baglietto L., Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., and Baglietto L.

Abstract

Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Method(s): An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Result(s): We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 x 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4-vs-Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4-vs-Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. Conclusion(s): We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.Copyright © 2019 The Author(s).

Published
2019

13. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.

Author

Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., Baglietto L., Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., and Baglietto L.

Abstract

Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Method(s): An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Result(s): We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 x 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4-vs-Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4-vs-Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. Conclusion(s): We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.Copyright © 2019 The Author(s).

Published
2019

14. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author

His, M, Viallon, V, Dossus, L, Gicquiau, A, Achaintre, D, Scalbert, A, Ferrari, P, Romieu, I, Onland-Moret, NC, Weiderpass, E, Dahm, CC, Overvad, K, Olsen, A, Tjonneland, A, Fournier, A, Rothwell, JA, Severi, G, Kuehn, T, Fortner, RT, Boeing, H, Trichopoulou, A, Karakatsani, A, Martimianaki, G, Masala, G, Sieri, S, Tumino, R, Vineis, P, Panico, S, van Gils, CH, Nost, TH, Sandanger, TM, Skeie, G, Quiros, JR, Agudo, A, Sanchez, M-J, Amiano, P, Maria Huerta, J, Ardanaz, E, Schmidt, JA, Travis, RC, Riboli, E, Tsilidis, KK, Christakoudi, S, Gunter, MJ, Rinaldi, S, His, M, Viallon, V, Dossus, L, Gicquiau, A, Achaintre, D, Scalbert, A, Ferrari, P, Romieu, I, Onland-Moret, NC, Weiderpass, E, Dahm, CC, Overvad, K, Olsen, A, Tjonneland, A, Fournier, A, Rothwell, JA, Severi, G, Kuehn, T, Fortner, RT, Boeing, H, Trichopoulou, A, Karakatsani, A, Martimianaki, G, Masala, G, Sieri, S, Tumino, R, Vineis, P, Panico, S, van Gils, CH, Nost, TH, Sandanger, TM, Skeie, G, Quiros, JR, Agudo, A, Sanchez, M-J, Amiano, P, Maria Huerta, J, Ardanaz, E, Schmidt, JA, Travis, RC, Riboli, E, Tsilidis, KK, Christakoudi, S, Gunter, MJ, and Rinaldi, S

Abstract

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Published
2019

15. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

Author

Johansson, A, Palli, D, Masala, G, Grioni, S, Agnoli, C, Tumino, R, Giurdanella, MC, Fasanelli, F, Sacerdote, C, Panico, S, Mattiello, A, Polidoro, S, Jones, ME, Schoemaker, MJ, Orr, N, Tomczyk, K, Johnson, N, Fletcher, O, Perduca, V, Baglietto, L, Dugue, P-A, Southey, MC, Giles, GG, English, DR, Milne, RL, Severi, G, Ambatipudi, S, Cuenin, C, Chajes, V, Romieu, I, Herceg, Z, Swerdlow, AJ, Vineis, P, Flanagan, JM, Johansson, A, Palli, D, Masala, G, Grioni, S, Agnoli, C, Tumino, R, Giurdanella, MC, Fasanelli, F, Sacerdote, C, Panico, S, Mattiello, A, Polidoro, S, Jones, ME, Schoemaker, MJ, Orr, N, Tomczyk, K, Johnson, N, Fletcher, O, Perduca, V, Baglietto, L, Dugue, P-A, Southey, MC, Giles, GG, English, DR, Milne, RL, Severi, G, Ambatipudi, S, Cuenin, C, Chajes, V, Romieu, I, Herceg, Z, Swerdlow, AJ, Vineis, P, and Flanagan, JM

Abstract

BACKGROUND: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. METHODS: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. RESULTS: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. CONCLUSION: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.

Published
2019

16. Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study

Author

Perrier, F, Viallon, V, Ambatipudi, S, Ghantous, A, Cuenin, C, Hernandez-Vargas, H, Chajes, V, Baglietto, L, Matejcic, M, Moreno-Macias, H, Kuehn, T, Boeing, H, Karakatsani, A, Kotanidou, A, Trichopoulou, A, Sieri, S, Panico, S, Fasanelli, F, Dolle, M, Onland-Moret, C, Sluijs, I, Weiderpass, E, Quiros, JR, Agudo, A, Huerta, JM, Ardanaz, E, Dorronsoro, M, Tong, TYN, Tsilidis, K, Riboli, E, Gunter, MJ, Herceg, Z, Ferrari, P, Romieu, I, Perrier, F, Viallon, V, Ambatipudi, S, Ghantous, A, Cuenin, C, Hernandez-Vargas, H, Chajes, V, Baglietto, L, Matejcic, M, Moreno-Macias, H, Kuehn, T, Boeing, H, Karakatsani, A, Kotanidou, A, Trichopoulou, A, Sieri, S, Panico, S, Fasanelli, F, Dolle, M, Onland-Moret, C, Sluijs, I, Weiderpass, E, Quiros, JR, Agudo, A, Huerta, JM, Ardanaz, E, Dorronsoro, M, Tong, TYN, Tsilidis, K, Riboli, E, Gunter, MJ, Herceg, Z, Ferrari, P, and Romieu, I

Abstract

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that diet

Published
2019

17. Time and age trends in smoking cessation in Europe

Author

Manzoli, L, Pesce, G, Marcon, A, Calciano, L, Perret, JL, Abramson, MJ, Bono, R, Bousquet, J, Fois, AG, Janson, C, Jarvis, D, Jogi, R, Leynaert, B, Nowak, D, Schlunssen, V, Urrutia-Landa, I, Verlato, G, Villani, S, Zuberbier, T, Minelli, C, Accordini, S, Boezen, M, Elger, B, Gleditsch, BA, Heijmans, B, Romieu, I, Thompson, J, Manzoli, L, Pesce, G, Marcon, A, Calciano, L, Perret, JL, Abramson, MJ, Bono, R, Bousquet, J, Fois, AG, Janson, C, Jarvis, D, Jogi, R, Leynaert, B, Nowak, D, Schlunssen, V, Urrutia-Landa, I, Verlato, G, Villani, S, Zuberbier, T, Minelli, C, Accordini, S, Boezen, M, Elger, B, Gleditsch, BA, Heijmans, B, Romieu, I, and Thompson, J

Abstract

BACKGROUND: Smoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010. METHODS: Data on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe). RESULTS: Overall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/year) compared to the other regions (range: 26.5-32.7 per 1,000/year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later. CONCLUSIONS: Our findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later li

Published
2019

18. Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies

Author

Bodelon, C, Ambatipudi, S, Dugue, P-A, Johansson, A, Sampson, JN, Hicks, B, Karlins, E, Hutchinson, A, Cuenin, C, Chajes, V, Southey, MC, Romieu, I, Giles, GG, English, D, Polidoro, S, Assumma, M, Baglietto, L, Vineis, P, Severi, G, Herceg, Z, Flanagan, JM, Milne, RL, Garcia-Closas, M, Bodelon, C, Ambatipudi, S, Dugue, P-A, Johansson, A, Sampson, JN, Hicks, B, Karlins, E, Hutchinson, A, Cuenin, C, Chajes, V, Southey, MC, Romieu, I, Giles, GG, English, D, Polidoro, S, Assumma, M, Baglietto, L, Vineis, P, Severi, G, Herceg, Z, Flanagan, JM, Milne, RL, and Garcia-Closas, M

Abstract

BACKGROUND: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date. METHODS: We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis (< 50, ≥ 50), estrogen receptor (ER) status (+/-), and time since blood collection (< 5, 5-10, > 10 years). The false discovery rate (q value) was used to account for multiple testing. RESULTS: The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since

Published
2019

19. Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Author

Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., Jenab, M., Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., and Jenab, M.

Abstract

Contains fulltext : 215343.pdf (publisher's version ) (Open Access), Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGFbeta) signaling was associated with CRC risk (P

Published
2019

20. Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Author

Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., Jenab, M., Fedirko, V., Mandle, H.B., Zhu, W., Hughes, D.J., Siddiq, A., Ferrari, P., Romieu, I., Riboli, E., Bueno-de-Mesquita, B., Duijnhoven, F. J. B. van, Siersema, P.D., Tjonneland, A., Olsen, A., Perduca, V., Carbonnel, F., Boutron-Ruault, M.C., Kuhn, T., Johnson, T., Krasimira, A., Trichopoulou, A., Makrythanasis, P., Thanos, D., Panico, S., Krogh, V., Sacerdote, C., Skeie, G., Weiderpass, E., Colorado-Yohar, S., Sala, N., Barricarte, A., Sanchez, M.J., Quiros, R., Amiano, P., Gylling, B., Harlid, S., Perez-Cornago, A., Heath, A.K., Tsilidis, K.K., Aune, D., Freisling, H., Murphy, N., Gunter, M.J., and Jenab, M.

Abstract

Contains fulltext : 215343.pdf (publisher's version ) (Open Access), Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGFbeta) signaling was associated with CRC risk (P

Published
2019

21. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author

Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hemon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quiros, J. R., Duell, E. J., Porta, M., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, Weimin, Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajes, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hemon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quiros, J. R., Duell, E. J., Porta, M., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, Weimin, Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajes, V.

Abstract

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.

Published
2018
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22. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author

Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.

Published
2018

23. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author

Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.

Published
2018

24. Identifying and correcting epigenetics measurements for systematic sources of variation

Author

Perrier, F, Novoloaca, A, Ambatipudi, S, Baglietto, L, Ghantous, A, Perduca, V, Barrdahl, M, Harlid, S, Ong, KK, Cardona, A, Polidoro, S, Nost, TH, Overvad, K, Omichessan, H, Dolle, M, Bamia, C, Maria Huerta, J, Vineis, P, Herceg, Z, Romieu, I, Ferrari, P, Perrier, F, Novoloaca, A, Ambatipudi, S, Baglietto, L, Ghantous, A, Perduca, V, Barrdahl, M, Harlid, S, Ong, KK, Cardona, A, Polidoro, S, Nost, TH, Overvad, K, Omichessan, H, Dolle, M, Bamia, C, Maria Huerta, J, Vineis, P, Herceg, Z, Romieu, I, and Ferrari, P

Abstract

BACKGROUND: Methylation measures quantified by microarray techniques can be affected by systematic variation due to the technical processing of samples, which may compromise the accuracy of the measurement process and contribute to bias the estimate of the association under investigation. The quantification of the contribution of the systematic source of variation is challenging in datasets characterized by hundreds of thousands of features.In this study, we introduce a method previously developed for the analysis of metabolomics data to evaluate the performance of existing normalizing techniques to correct for unwanted variation. Illumina Infinium HumanMethylation450K was used to acquire methylation levels in over 421,000 CpG sites for 902 study participants of a case-control study on breast cancer nested within the EPIC cohort. The principal component partial R-square (PC-PR2) analysis was used to identify and quantify the variability attributable to potential systematic sources of variation. Three correcting techniques, namely ComBat, surrogate variables analysis (SVA) and a linear regression model to compute residuals were applied. The impact of each correcting method on the association between smoking status and DNA methylation levels was evaluated, and results were compared with findings from a large meta-analysis. RESULTS: A sizeable proportion of systematic variability due to variables expressing 'batch' and 'sample position' within 'chip' was identified, with values of the partial R2 statistics equal to 9.5 and 11.4% of total variation, respectively. After application of ComBat or the residuals' methods, the contribution was 1.3 and 0.2%, respectively. The SVA technique resulted in a reduced variability due to 'batch' (1.3%) and 'sample position' (0.6%), and in a diminished variability attributable to 'chip' within a batch (0.9%). After ComBat or the residuals' corrections, a larger number of significant sites (k = 600 and k = 427, respectively) were associ

Published
2018

25. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author

Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.

Published
2018

26. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author

JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team B, UMC Utrecht, Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team B, UMC Utrecht, Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.

Published
2018

27. Biomarkers of folate and vitamin B12 and breast cancer risk : report from the EPIC cohort

Author

Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. B(as), Skeie, G., Amiano, P., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Quiros, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, Björn, Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., Chajes, V., Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. B(as), Skeie, G., Amiano, P., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Quiros, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, Björn, Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., and Chajes, V.

Abstract

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; P-trend=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 1.02-162; P-trend=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.

Published
2017
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28. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

Chajes, 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., Kuehn, T., Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H. B., Peeters, P. H., van Gils, C., Hjartaker, A., Olsen, K. Standahl, Barnung, R. Borgund, Barricarte, A., Redondo-Sanchez, D., Menendez, V., Amiano, P., Wennberg, Maria, Key, T., Khaw, K. T., Merritt, M. A., Riboli, E., Gunter, M. J., Romieu, I., Chajes, 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., Kuehn, T., Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H. B., Peeters, P. H., van Gils, C., Hjartaker, A., Olsen, K. Standahl, Barnung, R. Borgund, Barricarte, A., Redondo-Sanchez, D., Menendez, V., Amiano, P., Wennberg, Maria, Key, T., Khaw, K. T., Merritt, M. A., Riboli, E., Gunter, M. J., and Romieu, I.

Abstract

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 inc

Published
2017
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29. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., Romieu, I., Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., and Romieu, I.

Published
2017

30. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., Romieu, I., Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., and Romieu, I.

Published
2017

31. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Author

Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., Jenab, M., Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., and Jenab, M.

Abstract

Contains fulltext : 182723.pdf (Publisher’s version ) (Open Access), BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an approximately 20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modific

Published
2017

32. Biomarkers of folate and vitamin B12 and breast cancer risk : Report from the EPIC cohort

Author

Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., Chajès, V., Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., and Chajès, V.

Published
2017

33. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Author

Fedirko, V, Hao, QT, Gewirtz, AT, Stepien, M, Trichopoulou, A, Aleksandrova, K, Olsen, A, Tjonneland, A, Overvad, K, Carbonnel, F, Boutron-Ruault, M-C, Severi, G, Kuhn, T, Kaaks, R, Boeing, H, Bamia, C, Lagiou, P, Grioni, S, Panico, S, Palli, D, Tumino, R, Naccarati, A, Peeters, PH, Bueno-de-Mesquita, HB, Weiderpass, E, Castano, JMH, Barricarte, A, Sanchez, M-J, Dorronsoro, M, Quiros, JR, Agudo, A, Sjoberg, K, Ohlsson, B, Hemmingsson, O, Werner, M, Bradbury, KE, Khaw, K-T, Wareham, N, Tsilidis, KK, Aune, D, Scalbert, A, Romieu, I, Riboli, E, Jenab, M, Fedirko, V, Hao, QT, Gewirtz, AT, Stepien, M, Trichopoulou, A, Aleksandrova, K, Olsen, A, Tjonneland, A, Overvad, K, Carbonnel, F, Boutron-Ruault, M-C, Severi, G, Kuhn, T, Kaaks, R, Boeing, H, Bamia, C, Lagiou, P, Grioni, S, Panico, S, Palli, D, Tumino, R, Naccarati, A, Peeters, PH, Bueno-de-Mesquita, HB, Weiderpass, E, Castano, JMH, Barricarte, A, Sanchez, M-J, Dorronsoro, M, Quiros, JR, Agudo, A, Sjoberg, K, Ohlsson, B, Hemmingsson, O, Werner, M, Bradbury, KE, Khaw, K-T, Wareham, N, Tsilidis, KK, Aune, D, Scalbert, A, Romieu, I, Riboli, E, and Jenab, M

Abstract

BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

Published
2017

34. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Author

Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., Jenab, M., Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., and Jenab, M.

Abstract

Contains fulltext : 182723.pdf (Publisher’s version ) (Open Access), BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an approximately 20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modific

Published
2017

35. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., Romieu, I., Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., and Romieu, I.

Published
2017

36. Biomarkers of folate and vitamin B12 and breast cancer risk : Report from the EPIC cohort

Author

Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., Chajès, V., Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., and Chajès, V.

Published
2017

37. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Author

Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., Jenab, M., Freisling, H., Arnold, M., Soerjomataram, I., O'Doherty, M.G., Ordonez-Mena, J.M., Bamia, C., Kampman, E., Leitzmann, M., Romieu, I., Kee, F., Tsilidis, K., Tjonneland, A., Trichopoulou, A., Boffetta, P., Benetou, V., Bueno-de-Mesquita, H.B., Huerta, J.M., Brenner, H., Wilsgaard, T., and Jenab, M.

Abstract

Contains fulltext : 182723.pdf (Publisher’s version ) (Open Access), BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an approximately 20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modific

Published
2017

38. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team A, Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., Romieu, I., MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team A, Chajès, V., Assi, Nada, Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G.M., Baglietto, L., His, Mathilde, Boutron-Ruault, M.C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, Tilman, Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H B, Peeters, P H, van Gils, C, Hjartåker, Anette, Olsen, Karina Standahl, Barnung, Borgund R, Barricarte, A., Sanchez, D Redondo, Menéndez, Virginia, Amiano, P., Wennberg, Maria, Key, T., Khaw, Kay T., Merritt, Melissa A., Riboli, E., Gunter, Marc J., and Romieu, I.

Published
2017

39. Biomarkers of folate and vitamin B12 and breast cancer risk: Report from the EPIC cohort

Author

Epidemiology & Health Economics, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., Chajès, V., Epidemiology & Health Economics, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., and Chajès, V.

Published
2017

40. Strengthening the evidence base for nutrition and cancer in low and middle income countries

Author

Romieu, I., Margetts, B., Barquera, S., Gomes, F. da, Gunter, M., Hwalla, N., Kampman, E., Leitzmann, M., Potischman, N., Slimani, N., Vorster, E., Willett, W.C., Winichagoon, P., Wiseman, M., Romieu, I., Margetts, B., Barquera, S., Gomes, F. da, Gunter, M., Hwalla, N., Kampman, E., Leitzmann, M., Potischman, N., Slimani, N., Vorster, E., Willett, W.C., Winichagoon, P., and Wiseman, M.

Abstract

Contains fulltext : 182700.pdf (publisher's version ) (Open Access)

Published
2016

41. Epigenetic Signatures of Cigarette Smoking

Author

Joehanes, R. (Roby), Just, A.C. (Allan C.), Marioni, R.E. (Riccardo), Pilling, L.C. (Luke), Reynolds, L.M. (Lindsay), Mandaviya, P.R. (Pooja R.), Guan, W. (Weihua), Xu, T. (Tao), Elks, C.E. (Cathy), Aslibekyan, S. (Stella), Moreno-Macías, H. (Hortensia), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Dhingra, R. (Radhika), Yousefi, P. (Paul), Pankow, J.S. (James), Kunze, S. (Sonja), Shah, S.H. (Sonia H.), McRae, A.F. (Allan F.), Lohman, K. (Kurt), Sha, J. (Jin), Absher, D. (Devin), Ferrucci, L. (Luigi), Zhao, W. (Wei), Demerath, E.W. (Ellen), Bressler, J. (Jan), Grove, M.L. (Megan), Huan, T. (Tianxiao), Liu, C. (Chunyu), Mendelson, M.M. (Michael M.), Yao, C. (Chen), Kiel, D.P. (Douglas P.), Peters, A. (Annette), Wang-Sattler, R. (Rui), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Starr, J.M. (John), Ding, J. (Jingzhong), Rodriguez, C.J. (Carlos J.), Wareham, N.J. (Nick), Irvin, M.R. (Marguerite R.), Zhi, D. (Degui), Barrdahl, M. (Myrto), Vineis, P. (Paolo), Ambatipudi, S. (Srikant), Uitterlinden, A.G. (André), Hofman, A. (Albert), Schwartz, J. (Joel), Colicino, E. (Elena), Hou, L. (Lifang), Vokonas, P.S. (Pantel S.), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Bandinelli, S. (Stefania), Turner, S.T. (Stephen), Ware, E.B. (Erin B.), Smith, A.K. (Alicia K.), Klengel, T. (Torsten), Binder, E.B. (Elisabeth B.), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Gharib, S.A. (Sina), Swenson, B.R. (Brenton R.), Liang, L. (Liming), Demeo, D.L. (Dawn), O'Connor, G.T. (George), Herceg, Z. (Zdenko), Ressler, K.J. (Kerry J.), Conneely, K.N. (Karen N.), Sotoodehnia, N. (Nona), Kardia, S.L.R. (Sharon L. R.), Melzer, D. (David), Baccarelli, A.A. (Andrea), Meurs, J.B.J. (Joyce) van, Romieu, I. (Isabelle), Arnett, D.K. (Donna), Ong, K.K. (Ken K.), Liu, Y. (YongMei), Waldenberger, M. (Melanie), Deary, I.J. (Ian), Fornage, M. (Myriam), Levy, D. (Daniel), London, S.J. (Stephanie J.), Joehanes, R. (Roby), Just, A.C. (Allan C.), Marioni, R.E. (Riccardo), Pilling, L.C. (Luke), Reynolds, L.M. (Lindsay), Mandaviya, P.R. (Pooja R.), Guan, W. (Weihua), Xu, T. (Tao), Elks, C.E. (Cathy), Aslibekyan, S. (Stella), Moreno-Macías, H. (Hortensia), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Dhingra, R. (Radhika), Yousefi, P. (Paul), Pankow, J.S. (James), Kunze, S. (Sonja), Shah, S.H. (Sonia H.), McRae, A.F. (Allan F.), Lohman, K. (Kurt), Sha, J. (Jin), Absher, D. (Devin), Ferrucci, L. (Luigi), Zhao, W. (Wei), Demerath, E.W. (Ellen), Bressler, J. (Jan), Grove, M.L. (Megan), Huan, T. (Tianxiao), Liu, C. (Chunyu), Mendelson, M.M. (Michael M.), Yao, C. (Chen), Kiel, D.P. (Douglas P.), Peters, A. (Annette), Wang-Sattler, R. (Rui), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Starr, J.M. (John), Ding, J. (Jingzhong), Rodriguez, C.J. (Carlos J.), Wareham, N.J. (Nick), Irvin, M.R. (Marguerite R.), Zhi, D. (Degui), Barrdahl, M. (Myrto), Vineis, P. (Paolo), Ambatipudi, S. (Srikant), Uitterlinden, A.G. (André), Hofman, A. (Albert), Schwartz, J. (Joel), Colicino, E. (Elena), Hou, L. (Lifang), Vokonas, P.S. (Pantel S.), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Bandinelli, S. (Stefania), Turner, S.T. (Stephen), Ware, E.B. (Erin B.), Smith, A.K. (Alicia K.), Klengel, T. (Torsten), Binder, E.B. (Elisabeth B.), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Gharib, S.A. (Sina), Swenson, B.R. (Brenton R.), Liang, L. (Liming), Demeo, D.L. (Dawn), O'Connor, G.T. (George), Herceg, Z. (Zdenko), Ressler, K.J. (Kerry J.), Conneely, K.N. (Karen N.), Sotoodehnia, N. (Nona), Kardia, S.L.R. (Sharon L. R.), Melzer, D. (David), Baccarelli, A.A. (Andrea), Meurs, J.B.J. (Joyce) van, Romieu, I. (Isabelle), Arnett, D.K. (Donna), Ong, K.K. (Ken K.), Liu, Y. (YongMei), Waldenberger, M. (Melanie), Deary, I.J. (Ian), Fornage, M. (Myriam), Levy, D. (Daniel), and London, S.J. (Stephanie J.)

Abstract

Background-DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results-To comprehensively determine the association between cigarette smoki

Published
2016
Full Text
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42. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author

Couch, F.J. (Fergus), Kuchenbaecker, K.B. (Karoline), Michailidou, K. (Kyriaki), Mendoza-Fandino, G.A. (Gustavo A.), Nord, S. (Silje), Lilyquist, J. (Janna), Olswold, C. (Curtis), Hallberg, B. (Boubou), Agata, S. (Simona), Ahsan, H. (Habibul), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Barile, M. (Monica), Barkardottir, R.B. (Rosa), Barrowdale, D. (Daniel), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blank, S.V. (Stephanie), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria), Canzian, F. (Federico), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B.M.), Cox, A. (Angela), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, Devilee, P. (Peter), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dunning, A.M. (Alison), Eccles, D. (Diana), Ehrencrona, H. (Hans), Ekici, A.B. (Arif), Eliassen, H. (Heather), Ellis, S.D. (Steve), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Försti, A. (Asta), Fostira, F. (Florentia), Foulkes, W.D. (William), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gammon, M. (Marilie), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Gaudet, M.M. (Mia), Gayther, S.A. (Simon), Gerdes, A-M. (Anne-Marie), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Gunter, M.J. (Marc J.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Healey, S. (Sue), Heikkinen, T. (Tuomas), Henderson, B.E. (Brian), Herzog, J. (Josef), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje), Hoover, R.N. (Robert), Hopper, J.L. (John), Humphreys, K. (Keith), Hunter, D. (David), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Jones, M. (Michael), Kabisch, M. (Maria), Kar, S. (Siddhartha), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Khaw, K.T., Kibriya, M.G. (Muhammad), Knight, J.A. (Julia), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Lee, E. (Eunjung), Le Marchand, L. (Loic), Lester, K.J. (Kathryn), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lindstrom, S. (Stephen), Liu, J. (Jianjun), Long, J. (Jirong), Lubinski, J. (Jan), Mai, P.L. (Phuong), Makalic, E. (Enes), Malone, K.E. (Kathleen E.), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Martens, J.W.M. (John), McGuffog, L. (Lesley), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger), Miron, P. (Penelope), Montagna, M. (Marco), Mazoyer, S. (Sylvie), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Osorio, A. (Ana), Park, S.K. (Sue K.), Peeters, P.H.M., Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Phelan, C. (Catherine), Pilarski, R. (Robert), Poppe, B. (Bruce), Pykäs, K. (Katri), Radice, P. (Paolo), Rahman, N. (Nazneen), Rantala, J. (Johanna), Rappaport, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Romieu, I. (Isabelle), Rudolph, A. (Anja), Rutgers, E.J.T. (Emiel), Sanchez, M.-J. (Maria-Jose), Santella, R. (Regina), Sawyer, E.J. (Elinor), Schmidt, D.F. (Daniel), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schumacher, F.R. (Fredrick), Scott, R.J. (Rodney), Senter, L. (Leigha), Sharma, P. (Priyanka), Simard, J. (Jacques), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tamimi, R. (Rulla), Tapper, W. (William), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Thompson, D. (Deborah), Tihomirova, L. (Laima), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I.P. (Ian), Truong, T. (Thérèse), Tsimiklis, H. (Helen), Teulé, A. (A.), Tumino, R. (Rosario), Tung, N. (Nadine), Turnbull, C. (Clare), Ursin, G. (Giski), Deurzen, C.H.M. (Carolien) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wang, Z. (Zhaoming), Wang-Gohrke, S. (Shan), Weiderpass, E. (Elisabete), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice S.), Wildiers, H. (Hans), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Yao, S. (Song), Zamora, M.P. (Pilar), Zheng, W. (Wei), Hall, P. (Per), Kraft, P. (Peter), Vachon, C. (Celine), Slager, S. (Susan), Chenevix-Trench, G. (Georgia), Pharoah, P.D.P. (Paul), Monteiro, A.A.N. (Alvaro A. N.), García-Closas, M. (Montserrat), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), Couch, F.J. (Fergus), Kuchenbaecker, K.B. (Karoline), Michailidou, K. (Kyriaki), Mendoza-Fandino, G.A. (Gustavo A.), Nord, S. (Silje), Lilyquist, J. (Janna), Olswold, C. (Curtis), Hallberg, B. (Boubou), Agata, S. (Simona), Ahsan, H. (Habibul), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Barile, M. (Monica), Barkardottir, R.B. (Rosa), Barrowdale, D. (Daniel), Beckmann, L. (Lars), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blank, S.V. (Stephanie), Blomqvist, C. (Carl), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria), Canzian, F. (Federico), Carpenter, T.A. (Adrian), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B.M.), Cox, A. (Angela), Cross, S.S. (Simon), Cunningham, J.M. (Julie), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Darabi, H. (Hatef), Hoya, M. (Miguel) de La, Devilee, P. (Peter), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Santos Silva, I. (Isabel) dos, Dumont, M. (Martine), Dunning, A.M. (Alison), Eccles, D. (Diana), Ehrencrona, H. (Hans), Ekici, A.B. (Arif), Eliassen, H. (Heather), Ellis, S.D. (Steve), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Försti, A. (Asta), Fostira, F. (Florentia), Foulkes, W.D. (William), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Gabrielson, M. (Marike), Gammon, M. (Marilie), Ganz, P.A. (Patricia A.), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Gaudet, M.M. (Mia), Gayther, S.A. (Simon), Gerdes, A-M. (Anne-Marie), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Gunter, M.J. (Marc J.), Haeberle, L. (Lothar), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Healey, S. (Sue), Heikkinen, T. (Tuomas), Henderson, B.E. (Brian), Herzog, J. (Josef), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hooning, M.J. (Maartje), Hoover, R.N. (Robert), Hopper, J.L. (John), Humphreys, K. (Keith), Hunter, D. (David), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny N.), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Jones, M. (Michael), Kabisch, M. (Maria), Kar, S. (Siddhartha), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Khaw, K.T., Kibriya, M.G. (Muhammad), Knight, J.A. (Julia), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Lázaro, C. (Conxi), Lee, E. (Eunjung), Le Marchand, L. (Loic), Lester, K.J. (Kathryn), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Lindstrom, S. (Stephen), Liu, J. (Jianjun), Long, J. (Jirong), Lubinski, J. (Jan), Mai, P.L. (Phuong), Makalic, E. (Enes), Malone, K.E. (Kathleen E.), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Martens, J.W.M. (John), McGuffog, L. (Lesley), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger), Miron, P. (Penelope), Montagna, M. (Marco), Mazoyer, S. (Sylvie), Mulligan, A.-M. (Anna-Marie), Muranen, T.A. (Taru), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Osorio, A. (Ana), Park, S.K. (Sue K.), Peeters, P.H.M., Peissel, B. (Bernard), Peterlongo, P. (Paolo), Peto, J. (Julian), Phelan, C. (Catherine), Pilarski, R. (Robert), Poppe, B. (Bruce), Pykäs, K. (Katri), Radice, P. (Paolo), Rahman, N. (Nazneen), Rantala, J. (Johanna), Rappaport, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Romieu, I. (Isabelle), Rudolph, A. (Anja), Rutgers, E.J.T. (Emiel), Sanchez, M.-J. (Maria-Jose), Santella, R. (Regina), Sawyer, E.J. (Elinor), Schmidt, D.F. (Daniel), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Schumacher, F.R. (Fredrick), Scott, R.J. (Rodney), Senter, L. (Leigha), Sharma, P. (Priyanka), Simard, J. (Jacques), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Soucy, P. (Penny), Southey, M.C. (Melissa), Steinemann, D. (Doris), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Tamimi, R. (Rulla), Tapper, W. (William), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Thompson, D. (Deborah), Tihomirova, L. (Laima), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I.P. (Ian), Truong, T. (Thérèse), Tsimiklis, H. (Helen), Teulé, A. (A.), Tumino, R. (Rosario), Tung, N. (Nadine), Turnbull, C. (Clare), Ursin, G. (Giski), Deurzen, C.H.M. (Carolien) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wang, Z. (Zhaoming), Wang-Gohrke, S. (Shan), Weiderpass, E. (Elisabete), Weitzel, J.N. (Jeffrey), Whittemore, A.S. (Alice S.), Wildiers, H. (Hans), Winqvist, R. (Robert), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Yao, S. (Song), Zamora, M.P. (Pilar), Zheng, W. (Wei), Hall, P. (Per), Kraft, P. (Peter), Vachon, C. (Celine), Slager, S. (Susan), Chenevix-Trench, G. (Georgia), Pharoah, P.D.P. (Paul), Monteiro, A.A.N. (Alvaro A. N.), García-Closas, M. (Montserrat), Easton, D.F. (Douglas F.), and Antoniou, A.C. (Antonis)

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negati

Published
2016
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43. The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project.

Author

Bandera, EV, Fay, SH, Giovannucci, E, Leitzmann, MF, Marklew, R, McTiernan, A, Mullee, A, Romieu, I, Thune, I, Uauy, R, Wiseman, MJ, World Cancer Research Fund International Continuous Update Project Panel, Bandera, EV, Fay, SH, Giovannucci, E, Leitzmann, MF, Marklew, R, McTiernan, A, Mullee, A, Romieu, I, Thune, I, Uauy, R, Wiseman, MJ, and World Cancer Research Fund International Continuous Update Project Panel

Abstract

Anthropometric measures relating to body size, weight and composition are increasingly being associated with cancer risk and progression. Whilst practical in epidemiologic research, where population-level associations with disease are revealed, it is important to be aware that such measures are imperfect markers of the internal physiological processes that are the actual correlates of cancer development. Body mass index (BMI), the most commonly used marker for adiposity, may mask differences between lean and adipose tissue, or fat distribution, which varies across individuals, ethnicities, and stage in the lifespan. Other measures, such as weight gain in adulthood, waist circumference and waist-to-hip ratio, contribute information on adipose tissue distribution and insulin sensitivity. Single anthropometric measures do not capture maturational events, including the presence of critical windows of susceptibility (i.e., age of menarche and menopause), which presents a challenge in epidemiologic work. Integration of experimental research on underlying dynamic genetic, hormonal, and other non-nutritional mechanisms is necessary for a confident conclusion of the overall evidence in cancer development and progression. This article discusses the challenges confronted in evaluating and interpreting the current evidence linking anthropometric factors and cancer risk as a basis for issuing recommendations for cancer prevention.

Published
2016

44. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author

Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaeki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Foersti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, A-M, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, K-T, Kibriya, MG, Knight, JA, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkaes, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, M-J, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, CHM, van Rensburg, EJ, Varon-Mateeva, R, Wang, Z, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, Antoniou, AC, Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaeki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Foersti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, A-M, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, K-T, Kibriya, MG, Knight, JA, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkaes, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, M-J, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, CHM, van Rensburg, EJ, Varon-Mateeva, R, Wang, Z, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, and Antoniou, AC

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Published
2016

45. Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems

Author

Burton, A, Byrnes, G, Stone, J, Tamimi, RM, Heine, J, Vachon, C, Ozmen, V, Pereira, A, Garmendia, ML, Scott, C, Hipwell, JH, Dickens, C, Schuz, J, Aribal, ME, Bertrand, K, Kwong, A, Giles, GG, Hopper, J, Gomez, BP, Pollan, M, Teo, S-H, Mariapun, S, Taib, NAM, Lajous, M, Lopez-Riduara, R, Rice, M, Romieu, I, Flugelman, AA, Ursin, G, Qureshi, S, Ma, H, Lee, E, Sirous, R, Sirous, M, Lee, JW, Kim, J, Salem, D, Kamal, R, Hartman, M, Miao, H, Chia, K-S, Nagata, C, Vinayak, S, Ndumia, R, Van Gils, CH, Wanders, JOP, Peplonska, B, Bukowska, A, Allen, S, Vinnicombe, S, Moss, S, Chiarelli, AM, Linton, L, Maskarinec, G, Yaffe, MJ, Boyd, NF, Dos-Santos-Silva, I, McCormack, VA, Burton, A, Byrnes, G, Stone, J, Tamimi, RM, Heine, J, Vachon, C, Ozmen, V, Pereira, A, Garmendia, ML, Scott, C, Hipwell, JH, Dickens, C, Schuz, J, Aribal, ME, Bertrand, K, Kwong, A, Giles, GG, Hopper, J, Gomez, BP, Pollan, M, Teo, S-H, Mariapun, S, Taib, NAM, Lajous, M, Lopez-Riduara, R, Rice, M, Romieu, I, Flugelman, AA, Ursin, G, Qureshi, S, Ma, H, Lee, E, Sirous, R, Sirous, M, Lee, JW, Kim, J, Salem, D, Kamal, R, Hartman, M, Miao, H, Chia, K-S, Nagata, C, Vinayak, S, Ndumia, R, Van Gils, CH, Wanders, JOP, Peplonska, B, Bukowska, A, Allen, S, Vinnicombe, S, Moss, S, Chiarelli, AM, Linton, L, Maskarinec, G, Yaffe, MJ, Boyd, NF, Dos-Santos-Silva, I, and McCormack, VA

Abstract

BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types. METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences. RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p < 0.001). Conversion equations revealed differences converged to zero with increasing dense area. MD differences between screen-film and processed digital on the subsequent screening round were consistent with expected time-related MD declines. CONCLUSIONS: MD was slightly higher when measured on processed than on raw direct digital mammograms. Comparisons of MD on these image formats should ideally control for this non-constant and reader-specific difference.

Published
2016

46. Strengthening the evidence base for nutrition and cancer in low and middle income countries

Author

Romieu, I., Margetts, B., Barquera, S., Gomes, F. da, Gunter, M., Hwalla, N., Kampman, E., Leitzmann, M., Potischman, N., Slimani, N., Vorster, E., Willett, W.C., Winichagoon, P., Wiseman, M., Romieu, I., Margetts, B., Barquera, S., Gomes, F. da, Gunter, M., Hwalla, N., Kampman, E., Leitzmann, M., Potischman, N., Slimani, N., Vorster, E., Willett, W.C., Winichagoon, P., and Wiseman, M.

Abstract

Contains fulltext : 182700.pdf (publisher's version ) (Open Access)

Published
2016

47. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author

Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Forsti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, AM, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, Antoinette, Hooning, Maartje, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, Salima, Khaw, KT, Kibriya, MG, Knight, JA, Ko, YD, Konstantopoulou, I, Kosma, VM, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C (Conxi), Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J (Jingjing), Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, John, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B (Bruce), Pylkas, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, MJ (Maria-Jose), Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK (Marjanka), Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, Carolien, van Rensburg, EJ, Varon-Mateeva, R, Wang, ZM, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XHR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, Antoniou, AC, Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Forsti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, AM, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, Antoinette, Hooning, Maartje, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, Salima, Khaw, KT, Kibriya, MG, Knight, JA, Ko, YD, Konstantopoulou, I, Kosma, VM, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C (Conxi), Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J (Jingjing), Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, John, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B (Bruce), Pylkas, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, MJ (Maria-Jose), Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK (Marjanka), Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, Carolien, van Rensburg, EJ, Varon-Mateeva, R, Wang, ZM, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XHR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, and Antoniou, AC

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Published
2016

49. Dietary folate intake and breast cancer risk : European prospective investigation into cancer and nutrition

Author

de Batlle, J., Ferrari, P., Chajes, V., Park, J. Y., Slimani, N., McKenzie, F., Overvad, K., Roswall, N., Tjønneland, A., Boutron-Ruault, M. C., Clavel-Chapelon, F., Fagherazzi, G., Katzke, V., Kaaks, R., Bergmann, M. M., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Palli, D., Sieri, S., Panico, S., Tumino, R., Vineis, P., Bueno-de-Mesquita, H. B., Peeters, P. H., Hjartåker, A., Engeset, D., Weiderpass, E., Sánchez, S., Travier, N., Sanchez, M. J., Amiano, P., Chirlaque, M. D., Barricarte Gurrea, A., Khaw, K. T., Key, T. J., Bradbury, K. E., Ericson, U., Sonestedt, E., Van Guelpen, Bethany, Schneede, Jörn, Riboli, E., Romieu, I., de Batlle, J., Ferrari, P., Chajes, V., Park, J. Y., Slimani, N., McKenzie, F., Overvad, K., Roswall, N., Tjønneland, A., Boutron-Ruault, M. C., Clavel-Chapelon, F., Fagherazzi, G., Katzke, V., Kaaks, R., Bergmann, M. M., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Palli, D., Sieri, S., Panico, S., Tumino, R., Vineis, P., Bueno-de-Mesquita, H. B., Peeters, P. H., Hjartåker, A., Engeset, D., Weiderpass, E., Sánchez, S., Travier, N., Sanchez, M. J., Amiano, P., Chirlaque, M. D., Barricarte Gurrea, A., Khaw, K. T., Key, T. J., Bradbury, K. E., Ericson, U., Sonestedt, E., Van Guelpen, Bethany, Schneede, Jörn, Riboli, E., and Romieu, I.

Abstract

There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

Published
2015
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50. Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics : results from the EPIC cohort

Author

Ose, J., Fortner, R. T., Schock, H., Peeters, P. H., Onland-Moret, N. C., Bueno-de-Mesquita, H. B., Weiderpass, E., Gram, I. T., Overvad, K., Tjonneland, A., Dossus, L., Fournier, A., Baglietto, L., Trichopoulou, A., Benetou, V., Trichopoulos, D., Boeing, H., Masala, G., Krogh, V., Matiello, A., Tumino, R., Popovic, M., Obon-Santacana, M., Larranaga, N., Ardanaz, E., Sanchez, M-J, Menendez, V., Chirlaque, M-D, Travis, R. C., Khaw, K-T, Braendstedt, J., Idahl, Annika, Lundin, Eva, Rinaldi, S., Kuhn, E., Romieu, I., Gunter, M. J., Merritt, M. A., Riboli, E., Kaaks, R., Ose, J., Fortner, R. T., Schock, H., Peeters, P. H., Onland-Moret, N. C., Bueno-de-Mesquita, H. B., Weiderpass, E., Gram, I. T., Overvad, K., Tjonneland, A., Dossus, L., Fournier, A., Baglietto, L., Trichopoulou, A., Benetou, V., Trichopoulos, D., Boeing, H., Masala, G., Krogh, V., Matiello, A., Tumino, R., Popovic, M., Obon-Santacana, M., Larranaga, N., Ardanaz, E., Sanchez, M-J, Menendez, V., Chirlaque, M-D, Travis, R. C., Khaw, K-T, Braendstedt, J., Idahl, Annika, Lundin, Eva, Rinaldi, S., Kuhn, E., Romieu, I., Gunter, M. J., Merritt, M. A., Riboli, E., and Kaaks, R.

Abstract

Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n = 565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

Published
2015
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