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Study Suggests a Link Between Tattoos and Lymphoma 

Scientists have reported a possible correlation between having tattoos and getting lymphoma later in life. However, multiple caveats apply [1].

Looks cool, but what about safety?

Tattoos are a popular form of self-expression, and in recent years, they are becoming more prevalent, probably due to the loosening of social taboos. Current, effective techniques of tattoo removal also encourage people to get one because they don’t feel it’s permanent. However, tattoos are, in essence, an invasive procedure that involves being injected with various chemicals of questionable regulation. Hence, questions about health effects of tattoos are quite valid, and they are indeed abundant online. Amazingly, there is very little actual research that looks into that.

In a new study, researchers from the Lund University in Sweden leveraged their country’s robust system of medical records to shed some light on the issue. Among the people who had completed a vast medical questionnaire in 2021, they picked out all the cases of lymphoma and added three age- and sex-matched controls to each one. This design is known as a “matched case-control study.”

The researchers then looked at how cases of lymphoma correlated with tattoos in people aged 20-60, when this disease is the most prevalent. Lymphoma is a cancer of the lymphatic system that, unlike many other types of cancer, affects many young people. However, it is also one of the least deadly cancers.

A possible connection

At the beginning of their paper, the authors offered a tentative explanation to the possible link between tattoos and lymphoma. Tattoos are made using a cocktail of inks that may contain compounds such as primary aromatic amines (PAA) and polycyclic aromatic hydrocarbons along with toxic metals, including arsenic, chromium, cobalt, lead, and nickel. “A significant and concerning number of them,” according to the paper, are classified as carcinogens [2].

“We already know that when the tattoo ink is injected into the skin, the body interprets this as something foreign that should not be there and the immune system is activated,” said Christel Nielsen, the lead investigator. “A large part of the ink is transported away from the skin, to the lymph nodes where it is deposited.”

21% increase in risk

After controlling for several confounding variables, including sex, age, educational attainment, smoking status, hazardous occupation, and taking immunosuppressive drugs, the scientists found that people with tattoos had 21% more risk of getting a lymphoma. However, there is a lot to unpack in this result.

Most glaringly, it did not quite reach statistical significance, with a p-value of 0.067 (the commonly used threshold is 0.05). In matched case-control studies, the two main types of analysis are matched and unmatched. In the former, the matching that is performed at the design stage, where each case was matched to one or more controls, is preserved at the analysis stage. This controls better for possible confounding variables, but it also weakens the statistical power and widens the confidence interval. Still, it is considered the golden standard in such studies.

Unmatched analysis ignores the design-stage matching, increasing the statistical power but weakening the control over possible confounders. In this study, the fully adjusted unmatched analysis showed a statistically significant (p=0.04) 18% increase in the risk of lymphoma for people with tattoos.

Is removing tattoos even less safe?

The study reports several other interesting results. Most importantly, no correlation between lymphoma incidence and the overall tattooed area size was found. This surprised the researchers, who offered a following possible explanation: since there were usually several years between the time of assessing the tattoo status and the time of the lymphoma diagnosis, it is possible that during that time, some respondents acquired more tattoos, which would lead to misclassification. However, another possible explanation, Nielsen said, is that “a tattoo, regardless of size, triggers a low-grade inflammation in the body, which in turn can trigger cancer.”

Alarmingly, laser removal of tattoos showed an even stronger positive correlation with lymphoma incidence. Speculating about possible causes, the researchers cite reports that certain compounds in tattoo inks can be transformed by laser irradiation into other, more carcinogenic, compounds [3].

This study is the most rigorous to date to analyze the possible link between tattoos and lymphoma, but its findings are far from definitive. In addition to the questionable statistical significance of the results, populational studies can only demonstrate correlation but not causation. As the authors themselves note, more rigorous studies are needed. However, it is also common sense that having tattoos is less safe than not having them.

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Literature

[1] Nielsen, C., Jerkeman, M., & Jöud, A. S. (2024). Tattoos as a risk factor for malignant lymphoma: a population-based case–control study. EClinicalMedicine, 72.

[2] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC Monographs on the evaluation of carcinogenic risks to humans, 92, 1.

[3] Hauri, U., & Hohl, C. (2015). Photostability and breakdown products of pigments currently used in tattoo inks. Curr Probl Dermatol, 48, 164-169.

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Turn Bio Signs Agreement with HanAll Biopharma

Turn Biotechnologies, a developer of novel mRNA medicines and enabling technologies, today announced an exclusive global licensing agreement with pharmaceutical manufacturer HanAll Biopharma to develop groundbreaking medicines for the treatment of age-related eye and ear conditions.

The agreement, potentially exceeding $300 million in value for the first of multiple planned products, significantly expands the relationship between the companies. HanAll originally invested in Turn Bio in 2022.

A New Frontier in Age-Related Therapies

Products resulting from this collaboration will utilize Turn Bio’s Epigenetic Reprogramming of Age (ERA™) technology and its novel eTurna™ delivery platform. These cutting-edge technologies aim to restore optimal gene expression, combatting the effects of aging at the cellular level to treat and potentially cure chronic conditions.

“This partnership is a milestone for Turn Bio,” said company CEO Anja Krammer. “With HanAll’s support, we are accelerating the development of transformative therapies for eye and ear indications, which can benefit patients around the world. The potential impact on patients’ lives is enormous, and this is just the beginning.”

HanAll has closely monitored Turn Bio’s progress since its initial investment, recognizing the revolutionary potential of its epigenetic reprogramming technology.

“Turn Bio’s innovative approach to epigenetic reprogramming aligns closely with HanAll’s mission to explore innovative medicines to expand our therapeutic area,” said Sean Jeong, M.D., MBA, CEO of HanAll Biopharma. “Together, we are poised to pioneer new treatments that address critical unmet needs, particularly in aging-related diseases.”

Expanding Horizons in Regenerative Medicine

The partnership expands Turn Bio’s development, which had primarily focused on dermatology and immunology, to two other organs most commonly affected by age-related conditions. This means Turn Bio is working on therapies to treat and potentially cure most diseases caused by aging.

“The power of ERA™ technology is that it can rejuvenate cells in virtually any organ in the body,” said Turn Bio Co-founder Vittorio Sebastiano, the company’s head of research. “This agreement enables us to accelerate our development on multiple fronts to reverse the damage caused by aging and improve the quality of life for older patients.”

About Turn Biotechnologies

Turn Bio is a pre-clinical-stage company focused on repairing tissue at the cellular level and developing transformative drug delivery systems. The company’s proprietary mRNA-based ERA™ reprogramming technology aims to restore optimal gene expression by combatting the effects of aging in the epigenome. This potentially restores cells’ ability to prevent or treat disease and heal or regenerate tissue and helps to fight incurable chronic diseases. Its eTurna™ delivery platform uses unique formulations to precisely deliver cargo to specific organs, tissues, and cell types.

The company is completing pre-clinical research on tailored therapies targeting indications in dermatology and immunology, and developing therapies for ophthalmology, osteo-arthritis, and the muscular system. For more information, see www.turn.bio.

About HanAll Biopharma

HanAll Biopharma (KRX: 009420.KS) is a global biopharmaceutical company with presence in Korea, the USA, Japan, and Indonesia with the mission of making meaningful contributions to patients’ lives by introducing innovative, impactful medicines to address severe unmet medical needs. HanAll has been operating a portfolio of pharmaceutical products in the therapeutic areas of endocrine, circulatory, and urologic diseases for over 50 years.

HanAll has also expanded its focus to immunology, oncology, neurology, and ophthalmology to discover and develop innovative medicines for patients with diseases for which there are no effective treatments. One of its lead pipeline asset, HL161 (INN: batoclimab), an anti-FcRn antibody, is being developed in Phase 3 and Phase 2 trials across the world for the treatment of autoimmune diseases including generalized myasthenia gravis (gMG), thyroid eye disease (TED), chronic inflammatory demyelinating polyneuropathy (CIDP), and Graves’ disease (GD). Another lead asset, HL036 (INN: tanfanercept), a TNF inhibitor protein, is being evaluated in Phase 3 clinical studies in the US and is also being evaluated in China for the treatment of dry eye disease. HL161ANS, an anti-FcRn antibody targeting multiple indications, and HL192 (ATH-399A), a Nurr1 activator currently targeting Parkinson’s Disease, are also being evaluated in Phase 1 clinical studies (healthy volunteers). For further information, visit our website and connect with us on LinkedIn. For any media inquiries, please contact HanAll PR/IR (pr@hanall.comir@hanall.com).

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An Animal Without an Observed Mortality Increase

The researchers of a previous controversial paper on the naked mole-rat’s impressive longevity have returned, publishing data in GeroScience that bolsters their original findings.

A darling of longevity

The naked mole-rat, an unusually long-lived rodent species that lives in large colonies, has long been a mystery of gerontology, and investigations into its biology have yielded some surprising findings. Despite their small size, these hairless, wrinkled rodents are uniquely resistant to cardiac dysfunction [1] and cancer [2].

Five years ago, these three researchers published a paper detailing the naked mole-rat’s general resistance to all age-related causes of mortality, reporting that this animal’s risk of death does not increase with age [3]. However, as a previous comment [4] and these researchers note, most of the animals in that study were relatively young.

Missing death records, which originated prior to these researchers’ analysis, may have introduced bias into the study. The researchers responded by re-analyzing their data with left-censorship, a statistical technique that labels data gathered from before a certain point, which also occurs in this study and many other long-term survival studies [5]. Right-censorship, a statistical technique that labels data after a certain point (for example, if an animal is transferred away or is simply still alive), is also used in this study.

The same colonies, half a decade later

These researchers have continued the same animal husbandry practices among the same populations of animals as they did in their original 2018 paper [3]. Data from a total of 7,536 animals is included in this analysis, with complete birth and death (or right-censorship) information being available for 6,949. All of these animals were microchipped in order to verify individual identity. Much of the original data had to be updated in some way, but vital data for 3,222 of the previous paper’s animals was consistent between these studies.

One of the potential mortality-related factors that these researchers analyzed was colony size. Naked mole rats, like many insect species, are eusocial animals; in nature, they only leave to form new colonies of their own, and can never join other colonies because existing colonies act violently against intruders. Non-breeding animals in the smallest colonies had statistically greater mortality, particularly males, although this was not consistent from year to year. Larger animals also had a greater chance of survival. These differences are ascribed to social dynamics and violence rather than aging.

The researchers also analyzed mole rats from the Fukomys genus using the same statistical methods. These animals are somewhat similar to the naked mole-rat (Heterocephalus glaber), but they begin to die with age. Like with nearly other animal, their chances of death can be observed to increase over time. These species’ maximal lifespan is a bit over 20 years.

Naked mole rats, on the other hand, do not have this decreasing survival curve. While the animals do die over time, this rate seems to be unaffected by age. One animal died when it was nearly 31 years old, but the oldest animal that the researchers had at the time of data collection was just over 35 years old, and these researchers state that this is still not close to these animals’ median lifespan. These findings were confirmed whether or not they included data from the original 2018 paper.

We therefore maintain our original conclusion: that unlike every other species studied to date where mortality risk begins to increase long before median lifespan, naked mole-rat mortality hazard does not increase with age.

We still cannot know exactly how long a naked mole-rat lives on average under these researchers’ optimized animal husbandry practices. It may be that the naked mole rat does have a true median lifespan of 50, 60, or even beyond, when it dies of age-related diseases much later than other animals. Only time, or extremely advanced biological analysis, will tell. Meanwhile, researchers will continue to investigate this exceptionally long-lived animal and determine what of its abilities can be brought to human beings.

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Literature

[1] Can, E., Smith, M., Boukens, B. J., Coronel, R., Buffenstein, R., & Riegler, J. (2022). Naked mole-rats maintain cardiac function and body composition well into their fourth decade of life. Geroscience, 44(2), 731-746.

[2] Hadi, F., Smith, E. S. J., & Khaled, W. T. (2021). Naked mole-rats: Resistant to developing cancer or good at avoiding it?. The extraordinary biology of the naked mole-rat, 341-352.

[3] Ruby, J. G., Smith, M., & Buffenstein, R. (2018). Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age. elife, 7, e31157.

[4] Dammann, P., Scherag, A., Zak, N., Szafranski, K., Holtze, S., Begall, S., … & Platzer, M. (2019). Comment on ‘Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age’. Elife, 8, e45415.

[5] Ruby, J. G., Smith, M., & Buffenstein, R. (2019). Response to comment on ‘Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age’. Elife, 8, e47047.