A Case for Cigarettes Causing a Cornucopia of Diseases Outside the Lungs, Heart

— Does smoking have a causal role in epilepsy, IBD, rheumatoid arthritis, and more?

https://www.medpagetoday.com/pulmonology/smoking/99698

Mendelian randomization studies appeared to bring researchers closer to establishing a causal association between smoking and a wider range of diseases.

Genetic variation in smoking liability, subject to genetic alleles being randomly passed between generations, was associated with a staggering amount of conditions — many going beyond the lung and cardiovascular diseases traditionally linked to cigarette smoking.

Epilepsy, type 2 diabetes, and several circulatory system diseases, digestive diseases, musculoskeletal system diseases, eye diseases, and cancers were traced back to smoking in a meta-analysis performed by Susanna Larsson, PhD, epidemiologist at Uppsala University in Sweden, and Stephen Burgess, PhD, biostatistician at the University of Cambridge in England. Their report was published in eBioMedicine.

Smoking’s strongest associations were to conditions including abdominal aortic aneurysm, peripheral artery disease, chronic and acute pancreatitis, periodontitis, and subarachnoid hemorrhage.

Larsson and Burgess noted that the findings support prior observational studies and concluded that their study “provided genetic evidence to support that smoking is a causal risk factor for a wide range of diseases.”

Some diseases, like epilepsy, have less clear mechanisms that could relate them to a person’s genetic liability for smoking initiation and lifetime smoking.

Yet for some conditions like inflammatory bowel disease (IBD) and rheumatoid arthritis, a plausible mechanism may be systemic inflammation caused by burning cigarettes and the reactive oxygen species generated, according to Larsson and Burgess, who suggested that smoking may also be causing endothelial dysfunction and thrombogenesis by microbial composition and immune response.

The association between smoking and eye diseases, such as age-related macular degeneration and age-related cataracts, are also not fully understood. However, the authors suggest that these too may be related to oxidative stress and reactive oxygen species that can damage eye tissue.

According to Larsson and Burgess, reducing smoking initiation should be “a key public health priority.”

Many studies have documented the risks of cigarette smoke exposure, even when secondhand. Last year, a study of French women found that those who were exposed to smoky rooms as children were more likely to develop rheumatoid arthritis.

Furthermore, ex-smokers remain at higher risk of fair or poor health depending on the duration of their old smoking habits.

The present meta-analysis included 29 published Mendelian randomization studies and 123 separate analyses conducted from publicly available genome-wide association studies.

“An important strength of Mendelian randomization studies is that common biases inherent in observational studies, including confounding and reverse causation, are diminished because the exposure (e.g., smoking) of interest is proxied by genetic variants that are usually unrelated to other risk factors and are not changed by the development of disease,” the investigators explained.

Nevertheless, they acknowledged that their results were based on several statistical assumptions and were subject to potential competing risk bias.

Filed under: General Problems