Constitutional Genetics in Follicular Lymphoma

Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never develop Follicular lymphoma. It was observed that individuals who developed Follicular lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol 2014). High t(14;18) frequency in blood from healthy individuals could be a predictive biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells as well as failure of the micro-environment to control the proliferation of these cells are proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis of Follicular lymphoma patients has been significantly improved mainly with the development of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years. However, this lymphoma remains an incurable disease. The most commonly used tool for prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology.

Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. The investigators also plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk Follicular lymphoma individuals.


Eligibility Criteria:
Group "Genome Wide Association Studies"

Inclusion Criteria:

* Follicular lymphoma treated in first line therapy treated by immunochemotherapy (PRIMA, FOL05, MER1 and 2, control arm of RELEVANCE trial)
* Follicular lymphoma treated in first line therapy by Rituximab and Lenalidomide as part of the investigational arm of RELEVANCE trial
* Available constitutional DNA samples for GWAS analysis with an accurate consent form for such genetic study
* Available biological and clinical characteristics at diagnosis with a follow-up of the patient for event free survival analysis
* 18 years of age or older

Exclusion Criteria:

* A non-follicular lymphoma histology according to WHO 2016 classification (grade 1, 2, 3a follicular lymphoma)
* Relapsed follicular lymphoma
* Patients without an accurate consent form for constitutional genetic study
* Patients with no available biological or clinical data and follow-up for the outcome analysis

Group "EPIC"

Inclusion Criteria:

* Included in the EPIC Cohort (European Prospective Investigation into Cancer and nutrition study between 1992 and 2000)
* Available constitutional DNA samples with an accurate consent form for such genetic study
* 18 years of age or older

Exclusion Criteria:

* Patients without an accurate consent form for constitutional genetic study
* Patients with no available biological or clinical data and follow-up for the outcome analysis