Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study

Abstract

Purpose Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression. Methods Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status. Results Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR− tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites. Conclusions Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.

DNA methylation signatures of breast cancer in peripheral T-cells

“…Since no information regarding the current and past smoking history of our patients was available, smoking was not included as a covariate in the model which is a limitation of our data. A larger follow up study should include smoking data since tobacco smoke is reported to alter the methylation state of tumoral DNA [ 42 ]. Using our current cohort, the number of samples did not allow sufficient power of analysis based on TNM staging.…”

Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study

“…For example, the ER − basal-like intrinsic subtype is more prevalent among African-American and younger patients [7], carries a high frequency of p53 gene mutations [39, 40] and is relatively deficient in DNA repair and more genetically unstable [41]; it seems plausible that the insult of tobacco smoke chemicals could potentiate this instability, leading to more recurrences. The smoking-breast cancer mortality associations may also be mediated by smoking-induced alterations in methylation of breast tumor DNA; a recent study found that current smokers with hormone receptor negative breast tumors exhibited primarily CpG hypomethylation compared to never smokers [42]. From studies of head and neck and lung cancers, it has also been hypothesized that smoking may reduce treatment efficacy, in particular responses to radiation and chemotherapy treatments [43, 44].…”

Liposomal Drug Delivery Systems and Anticancer Drugs

“…Cancer is responsible for ~3.4 million deaths worldwide [ 22 ]. Some of the well-known causes for cancer disease are smoking (causing lung [ 23 ], breast [ 24 ], and ovarian cancer [ 25 ]), being overweight or obese (associated with 13 types of cancer disease, such as breast cancer, kidney, womb and bowel cancers), intake of processed meat [ 26 ], radiation (causes skin cancer) [ 27 ], family history, stress, environmental factors, and chance [ 28 ].…”