|Grant Number:||5R03CA143947-02 Interpret this number|
|Primary Investigator:||Bracci, Paige|
|Organization:||University Of California, San Francisco|
|Project Title:||Energy Balance and Nutrigenetic Analysis of Non-Hodgkin Lymphoma|
DESCRIPTION (provided by applicant): Energy balance and nutrigenetic analyses of non-Hodgkin lymphoma In the U.S, non-Hodgkin lymphoma (NHL) is the most common hematopoietic cancer in adults with >60,000 cases newly diagnosed each year. A few studies have identified some components of energy-balance: diet, exercise and obesity that are associated with NHL risk. Laboratory data show that these factors also can affect immune and inflammatory processes that may influence lymphomagenesis. Genetic susceptibility for NHL and NHL subtypes has been identified in biologically plausible pathways including immune function, inflammation, oxidative processes and in DNA repair and integrity. However, no comprehensive analyses have been conducted that integrate energy-balance factors, genetics and NHL risk. Our innovative analyses will leverage epidemiologic and genetic data already collected during in-person interviews in our large population-based case-control NHL study (2055 cases, 2081 controls) to: Aim 1) analyze diet, anthropometric and exercise data to determine associations with risk of NHL and NHL subtypes and; Aim 2) analyze gene-environment interactions to determine if single nucleotide polymorphisms (SNP) in dietary response and metabolism genes, and in inflammation and immune function genes modify the association between factors in Aim 1 and NHL risk. Unconditional logistic regression adjusted for potential confounding and effect modification will be used to obtain odds ratios as estimates of relative risk and to explore differential effects by subgroups including NHL subtypes. Energy-adjusted methods and statistical methods to assess misreporting of food frequency questionnaire (FFQ) data also will be used for analyses of nutrient data. The studys major strengths are: 1) a rich epidemiologic dataset that includes already collected exercise, anthropometrics and dietary history data collected using a validated and calibrated FFQ with frequency and portion size for specific foods, supplement use, cooking methods and macro and micronutrients computed using a relational food composition database; 2) demographic and other data available to evaluate confounding and effect modification and; 3) DNA already analyzed for SNPs in 146 genes in biologic pathways that may be relevant to the nutrigenetics of NHL. Results from the comprehensive analyses within our large well-defined study population will provide insight into modifiable dietary-related risk factors and nutrigenetics associated with NHL and common NHL subtypes that can help clarify the role of bioactive foods in lymphomagenesis. The information from our work also will be useful to help generate hypotheses for future research, to direct functional studies, to help identify key biologic pathways that alter susceptibility, and will be directly applicable to prevention and intervention programs to reduce NHL incidence. In addition, future pooled analyses of these and related data are planned within the InterLymph Consortium to confirm findings and to increase power and sample size for analyses by rare NHL subtypes, and for low-frequency exposures that cannot be investigated adequately in individual studies. PUBLIC HEALTH RELEVANCE: Project Narrative Incidence of non-Hodgkin lymphoma (NHL) has nearly doubled over the past 40 years and few risk factors have been established other than those associated with severe immunosuppression and some rare genetic conditions. There is growing evidence that the modifiable lifestyle factors of diet, physical activity and obesity are associated with NHL risk and that these factors act in genetic pathways that also have been associated with NHL risk. Clarifying the role that these modifiable factors play in risk of NHL and NHL subtypes will improve our understanding of NHL development, help to generate new hypotheses for future research and will be directly applicable to prevention, intervention and screening programs with a goal to reduce NHL incidence.
Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development.
Authors: Schuetz JM, Daley D, Leach S, Conde L, Berry BR, Gallagher RP, Connors JM, Gascoyne RD, Bracci PM, Skibola CF, Spinelli JJ, Brooks-Wilson AR
Source: PLoS One, 2013;8(9), p. e75170.
EPub date: 2013 Sep 30.
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
Authors: Berndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, Cozen W, Monnereau A, Wang SS, Kelly RS, Lan Q, Teras LR, Chatterjee N, Chung CC, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Armstrong BK, Cocco P, Zhang Y, Severi G, Zeleniuch-Jacquotte A, Lawrence C, Burdette L, Yuenger J, Hutchinson A, Jacobs KB, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Wang AH, Smedby KE, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Jones B, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Holly EA, Smith MT, Jackson RD, Tinker LF, Benavente Y, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Rabe KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Lanasa MC, Spector LG, Leis JF, Cunningham JM, Weinberg JB, Morrison VA, Caporaso NE, Norman AD, Linet MS, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Trichopoulos D, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RC, Travis RC, Giles GG, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Offit K, Zelenetz A, Klein RJ, Spinelli JJ, Bertrand KA, Laden F, Giovannucci E, Kraft P, Kricker A, Turner J, Vajdic CM, Ennas MG, Ferri GM, Miligi L, Liang L, Sampson J, Crouch S, Park JH, North KE, Cox A, Snowden JA, Wright J, Carracedo A, Lopez-Otin C, Bea S, Salaverria I, Martin-Garcia D, Campo E, Fraumeni JF Jr, de Sanjose S, Hjalgrim H, Cerhan JR, Chanock SJ, Rothman N, Slager SL
Source: Nat Genet, 2013 Aug;45(8), p. 868-76.
EPub date: 2013 Jun 16.
Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.
Authors: Kane EV, Bernstein L, Bracci PM, Cerhan JR, Costas L, Dal Maso L, Holly EA, La Vecchia C, Matsuo K, Sanjose S, Spinelli JJ, Wang SS, Zhang Y, Zheng T, Roman E, Kricker A, InterLymph Consortium
Source: Ann Oncol, 2013 Feb;24(2), p. 433-41.
EPub date: 2012 Sep 11.
Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.
Authors: Kane EV, Roman E, Becker N, Bernstein L, Boffetta P, Bracci PM, Cerhan JR, Chiu BC, Cocco P, Costas L, Foretova L, Holly EA, La Vecchia C, Matsuo K, Maynadie M, Sanjose S, Spinelli JJ, Staines A, Talamini R, Wang SS, Zhang Y, Zheng T, Kricker A, InterLymph Consortium
Source: Ann Oncol, 2012 Sep;23(9), p. 2362-74.
EPub date: 2012 Jul 10.
Intake of vitamins D and A and calcium and risk of non-Hodgkin lymphoma: San Francisco Bay Area population-based case-control study.
Authors: Mikhak B, Bracci PM, Gong Z
Source: Nutr Cancer, 2012;64(5), p. 674-84.
EPub date: 2012 Jun 14.