39P - DNA methylation of the CYP1A1 and GSTP1 genes and incidence of major cancers (lung, breast and colon) in the PREDIMED-Valencia study

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer
Colon Cancer
Lung and other Thoracic Tumours
Presenter Judith Begona Ramirez Sabio
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors J.B. Ramirez Sabio1, J.V. Sorlí2, C. Ortega-Azorín2, I. González-Monje2, E.M. Asensio2, R. Barragán2, R. Fernández-Carrión2, C. Gallego2, R. Estruch3, Ó. Coltell4, O. Portolés2, D. Corella2
  • 1Medical Oncology Unit, Hospital de Sagunt, 46520 - Pto. Sagunto/ES
  • 2Preventive Medicine And Ciber Fisiopatología De La Obesidad Y Nutrición, University of Valencia, 46010 - Valencia/ES
  • 3Internal Medicine, Hospital Clinic de Barcelona, Barcelona/ES
  • 4Computer Languages And Systems. School Of Technology And Experimental Sciences, Jaume I University, Castellón/ES

Abstract

Background

DNA methylation is an epigenetic determinant of gene expression. Cytochrome P450 (CYP1A1) is a phase 1 xenobiotic metabolizing enzyme. Glutathione S-transferase P1 (GSTP1) detoxifies metabolites and regulates cellular chemical stress and death. Methylation changes in these genes could play a role in the incidence of cancer. Our aims were to analyze DNA-methylation of selected CpG islands in the CYP1A1 and GSTP1 genes at baseline in subjects who had incident cancer and paired controls, and to determine if DNA methylation in cancer patients changed from baseline to the time close to cancer diagnosis.

Methods

We followed-up 1094 subjects (aged: 67±6years) of the PREDIMED-Valencia study prospectively from 2003 to 2014. Cancer incidence was a secondary outcome in our trial. We analyzed 69 cases of incident cancer (lung, breast and colon) during this follow-up period, and 69 paired controls free of cancer. We analyzed DNA-methylation levels of the CYP1A1 and GSTP1 genes at baseline in both groups. Quantitative DNA methylation analysis was undertaken by MALDI-TOF mass spectrometry. We evaluated methylation levels on chromosome 15 (region: 74726090 -74726460 base pairs from promoter) and chromosome 11 (region: 67583556-67583896 base pairs from promoter).

Results

We detected statistically significant differences in DNA methylation levels at baseline in the CYP1A1 and GSTP1 genes between cancer cases and controls (P=0.008 for the CpG site 26-27 of the CYP1A1 gene and P=0.049 for the CpG 10-11 island at the GSTP1 gene). We detected statistically significant changes in DNA methylation prospectively in cancer patients. DNA methylation at the CpG 4 (CYP1A1 gene) was 0.020±0.034 at baseline vs 0.006±0.013 close to cancer diagnosis (P=0.044). For the GSTP1 gene, methylation of the CpG 34-39 prospectively increased from 0.327±0.046 at baseline to 0.345±0.053 (P=0.014) close to cancer diagnosis.

Conclusions

We have detected differences in DNA-methylation of selected CpG Islands of the CYP1A1 and GSTP1 genes at baseline, between future diagnosed cancer subjects and cancer-free controls. Moreover, in patients subsequently diagnosed with cancer, a change in DNA methylation was observed between baseline and close to the time of cancer diagnosis. This suggests a dynamic influence of DNA methylation that could be modulated for prevention.

Clinical trial identification

Controlled-trials.com number ISRCTN35739639

Legal entity responsible for the study

Spanish Government's Instituto de Salud Carlos III and University of Valencia

Funding

Instituto de Salud Carlos III

Disclosure

All authors have declared no conflicts of interest.