Abstract 42: Associations between breast cancer survival and SNPs identified through GWAS meta-analyses for metabolic and cardiovascular diseases/traits.

Background: Early detection and improvement of treatments have resulted in an increasing population of cancer survivors in Western countries. However, if factors associated with cancer incidence have been extensively studied, those related to overall and disease-free survival are still largely unknown. Most of the recommendations given to cancer patients are generally based on what is known about cancer risk factors and not on studies directly examining prognostic factors. Nevertheless, tumor cells have a different metabolism from normal cells and factors that could favor cell progression and invasion are therefore probably not the same as those associated with carcinogenesis. Among lifestyle factors that could influence breast cancer survival, excess weight and obesity have been the most studied and were associated with poor prognosis among women with breast cancer. However, physiological mechanisms that could explain these associations are not yet completely identified.

Objectives: The aim of the current project is to examine the association between genetic polymorphisms in obesity-related pathways and breast cancer recurrence and survival within the French prospective E3N cohort.

Setting & Methods: The E3N cohort is an ongoing prospective study investigating risk factors for cancer and other chronic diseases. The 98,995 participants were recruited in 1990-91 among women aged 40-65 years, living in France and insured with a national health insurance plan covering mostly teachers. At recruitment, women returned a self-administered questionnaire about lifestyle and reproductive factors, body build, and past medical history. Follow-up questionnaires were sent every 24-36 months thereafter (participation rate ˜80% at each questionnaire). Seventy percent of the participants provided biological material, in the form of a blood (N=23,073) or a saliva (N=47,280) sample. Samples from 1,718 women with diagnosed incident breast cancer were genotyped for 196,725 genetic polymorphisms identified in published GWAS on metabolic and cardiovascular diseases/traits (“Metabochip”, Illumina iSelect). Causes of death were identified through death certificates and linkage with the National Death Registry and recurrences, metastases or second primary tumors were self-reported and validated with pathology reports. To date, 284 breast cancer cases are deceased or have reported a recurrence, metastases or a second tumor. Moreover, information on cancer treatments was collected though a specific questionnaire already sent to 85% of the cases and is currently being validated through medical records and linkage with the health insurance database of reimbursed drugs. Statistical analyses are ongoing and their results will be presented at the meeting. The risk of recurrence and breast cancer-specific and overall mortality by genotype categories is being estimated by Cox proportional hazard models adjusted for known prognostic factors (age and year at diagnosis, tumor characteristics, educational level, type of treatment, menopausal status). Subsequent analyses on gene-environment interactions will be performed.

Conclusions: The results of the study will allow identification of genetic polymorphisms associated with excess weight, obesity and weight gain and related to breast cancer recurrence and survival. The results will also permit a better understanding of mechanisms underlying the association between obesity and breast cancer prognosis and the classification of patients in groups with high risk of recurrence and poor survival.

Citation Format: Laure Dossus, David Cox, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon. Associations between breast cancer survival and SNPs identified through GWAS meta-analyses for metabolic and cardiovascular diseases/traits. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 42.