A single cytosine–guanine dinucleotide (CpG) site within coagulation factor II (thrombin) receptor-like 3 (F2RL3) was recently found to be hypomethylated in peripheral blood genomic DNA from smokers compared with former and non-smokers. We performed two epigenome-wide association studies (EWAS) nested in a prospective healthy cohort using the Illumina 450K Methylation Beadchip. The two populations consisted of matched pairs of healthy individuals (n = 374), of which half went on to develop breast or colon cancer. The association was analysed between methylation and smoking status, as well as cancer risk. In addition to the same locus in F2RL3, we report several loci that are hypomethylated in smokers compared with former and non-smokers, including an intragenic region of the aryl hydrocarbon receptor repressor gene (AHRR; cg05575921, P = 2.31 × 10⁻¹⁵; effect size = 14–17%), an intergenic CpG island on 2q37.1 (cg21566642, P = 3.73 × 10⁻¹³; effect size = 12%) and a further intergenic region at 6p21.33 (cg06126421, P = 4.96 × 10⁻¹¹, effect size = 7–8%). Bisulphite pyrosequencing validated six loci in a further independent population of healthy individuals (n = 180). Methylation levels in AHRR were also significantly decreased (P < 0.001) and expression increased (P = 0.0047) in the lung tissue of current smokers compared with non-smokers. This was further validated in a mouse model of smoke exposure. We observed an association with breast cancer risk for the 2q37.1 locus (P = 0.003, adjusted for the smoking status), but not for the other loci associated with smoking. These data show that smoking has a direct effect on the epigenome in lung tissue, which is also detectable in peripheral blood DNA and may contribute to cancer risk.

The COVID‐19 pandemic and subsequent lockdown and social distancing led to changes to breastfeeding support available to women in the United Kingdom. Face‐to‐face professional support was reduced, and face‐to‐face peer support was cancelled. Anecdotal media accounts highlighted practices separating some mothers and babies in hospitals, alongside inaccurate stories of the safety of breastfeeding circulating. Meanwhile, new families were confined to their homes, separated from families and support networks. Given that we know breastfeeding is best supported by practices that keep mother and baby together, high‐quality professional and peer‐to‐peer support, and positive maternal well‐being, it is important to understand the impact of the pandemic upon the ability to breastfeed. To explore this, we conducted an online survey with 1219 breastfeeding mothers in the United Kingdom with a baby 0–12 months old to understand the impact of the pandemic upon breastfeeding duration, experiences and support. The results highlighted two very different experiences: 41.8% of mothers felt that breastfeeding was protected due to lockdown, but 27.0% of mothers struggled to get support and had numerous barriers stemming from lockdown with some stopped breastfeeding before they were ready. Mothers with a lower education, with more challenging living circumstances and from Black and minority ethnic backgrounds were more likely to find the impact of lockdown challenging and stop breastfeeding. The findings are vital in understanding how we now support those women who may be grieving their loss of breastfeeding and are affected by their negative experiences and how we can learn from those with a positive experience to make sure all breastfeeding women are better supported if similar future events arise.

Background: Most biomarkers of exposure tend to have short half-lives. This includes cotinine, a metabolite of nicotine widely used to assess smoke exposure. Cotinine is thus unsuitable as a determinant of past exposure to cigarette smoke. Methods: We used bisulphite pyrosequencing of a set of four genomic loci (AHRR, 6p21, and two at 2q37) that had differential DNA methylation levels in peripheral blood DNA dependent on tobacco exposure to create a predictive model of smoking status. Results: Combining four gene loci into a single methylation index provided high positive predictive and sensitivity values for predicting former smoking status in both test (n = 81) and validation (n = 180) sample sets. Conclusions: This study provides a direct molecular measure of prior exposure to tobacco that can be performed using the quantitative approach of bisulphite pyrosequencing. Epigenetic changes that are detectable in blood may more generally act as molecular biomarkers for other exposures that are also difficult to quantify in epidemiological studies.

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation.

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence‐based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting ‘breastfeeding denialism’ arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation.