DNA methylation level in blood and relations to breast cancer, risk factors and environmental exposure in Greenlandic Inuit women

• Published in: Basic & Clinical Pharmacology & Toxicology
• Main Authors: Wielsøe, Maria, Tarantini, Letizia, Bollati, Valentina, Long, Manhai, Bonefeld-Jørgensen, Eva Cecilie
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2020
• Subjects: CELL DNA; COLORECTAL ADENOMA; GENE; HYPOMETHYLATION; LEUKOCYTE DNA; NEW-YORK SITE; PERIPHERAL-BLOOD; PERSISTENT ORGANIC POLLUTANTS; PROMOTER HYPERMETHYLATION; SISTERS DISCORDANT; arctic inuit; circadian genes; repetitive elements; tumour suppressor genes; Arctic; greenlandic; inuit
• Online Access: https://pure.au.dk/portal/da/publications/dna-methylation-level-in-blood-and-relations-to-breast-cancer-risk-factors-and-environmental-exposure-in-greenlandic-inuit-women(183aabaa-835e-4cdc-8423-848ad978ed8a).html; https://doi.org/10.1111/bcpt.13424; https://pure.au.dk/ws/files/220258442/bcpt.13424.pdf

Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case-control study evaluated blood methylation level of two repetitive elements and selected breast cancer-related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE-1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE-1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.