Skin cancer is the most common form of cancer in the United States.

Melanoma accounts for just 1% of skin cancer cases, but it causes the majority of deaths from this type of disease.

There are an estimated 96,480 new melanoma diagnoses each year in the United States, and according to the authors of a recent study, the rates of malignant melanoma are rising faster than those of any other cancer.

In the U.S. there were 8,650 deaths due to melanoma in 2009 — and despite improved treatments and better 5-year survival rates, there were around 10,130 deaths from this cause in 2016.

Although scientists have identified risk factors associated with melanoma, such as fair skin, family history, and sun exposure, it is not clear why incidence rates are rising.

Because obesity is a risk factor for certain cancers, some researchers have asked whether it might also raise melanoma risk. However, to date, studies have failed to find a clear-cut association.

Revisiting old data

A Swedish study from 2009 found that women with obesity who undergo bariatric surgery have a reduced risk of cancer. When the results were published, there was not enough data to assess whether weight loss surgery impacted skin cancer risk, specifically.

However, researchers have continued to follow the participants in the original study, now for an average of 18.1 years. A team recently revisited the dataset in an effort to “investigate the association between bariatric surgery and skin cancer, including melanoma.”

In total, the new analysis included data from 2,007 individuals with obesity who underwent bariatric surgery and 2,040 matched control participants who had obesity but who only received conventional treatment, such as lifestyle advice, at their primary healthcare centers. The scientists recently published their findings in the journal JAMA Dermatology.

Individuals in the bariatric surgery group, at the 15-year follow-up, had lost an average of 47.6 pounds (21.6 kilograms). Those in the control group had remained at a relatively constant weight, with an average loss or gain that never exceeded 6.6 pounds (3 kilograms).

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Overall, 23 individuals in the surgery group had developed malignant skin cancer — squamous cell carcinoma or malignant melanoma. In the control group, 45 individuals had developed this type of disease.

The researchers found that the largest difference between the two groups concerned malignant melanoma. In the control group, there were 29 cases of the disease, while in the surgery group, there were just 12 cases. This equates to a 57% reduction in malignant melanoma risk.

Why does obesity increase risk?

Scientists will need to carry out more research to understand the mechanisms that underpin the relationship between obesity and skin cancer. However, the authors outline several factors that could be involved.

One theory concerns inflammation; they explain that “Obesity leads to chronic systemic inflammation, which could provide a permissive environment for tumor growth.”

Lifestyle factors, such as changes to diet following surgery, might also help explain this link.

Similarly, obesity is associated with a sedentary lifestyle — itself linked with increased cancer incidence and mortality. Following bariatric surgery, individuals may increase their levels of physical activity, thereby reducing cancer risk.

The current study has a number of strengths, including the long follow-up duration and the use of matched controls. However, there are also certain limitations; for instance, the scientists did not use randomization.

In an ideal world, it is best to assign participants to the control or experimental groups randomly. For this study, it was not possible, primarily because when the study began in the 1980s, the mortality rate for weight loss surgery was relatively high, so randomization would have been unethical.

It is also worth noting that, although the melanoma rates between the two groups were significantly different, the overall number of cases was small — in total, there were just 41 cases of melanoma. Scientists will need to continue this line of investigation to gather more evidence. For now, the authors conclude:

“These findings suggest that melanoma incidence is significantly reduced in patients with obesity after bariatric surgery and may lead to a better understanding of melanoma and preventable risk factors.”

The post Weight loss surgery reduces skin cancer risk appeared first on MyMedicPlus.

The cell polarity protein Par3 controls mechanic changes in the skin and plays an important role in cell division. Malfunction can lead to DNA damages. The balance of the system is of great importance: while too much differentiation leads to loss of stem cells and therefore premature aging, too many cell divisions can be a cause of skin cancer. The new study by a team around Sandra Iden about how polarity regulators control cellular mechanics in the skin was now published in Nature Communications.

The skin serves as a crucial barrier to the outside world. Its task is not only to keep pathogens or toxic chemicals out of the body, but also to keep water inside and maintain hydration. In order to function properly, the skin epidermis constantly needs to keep a balance of cells it sheds off and new cells that replenish the lost ones. The skin epidermis is made up of several layers with different functions. Skin stem cells are responsible for the self-renewing capacity of the skin.

In a previous study, the researchers showed that inactivation of the polarity protein Par3 resulted in a decline of stem cells, impaired skin homeostasis and premature skin aging. Back then, however, the underlying mechanisms remained unclear. ‘We were now able to show that Par3 has a direct influence on the homeostasis of the skin by controlling the mechanical properties of keratinocytes, the main skin epithelial cell,’ said leading scientist of the study Dr Sandra Iden. The polarity protein Par3 controls the mechanical properties of the main skin epithelial cells, called keratinocytes. It has functions that are conserved from worms and flies to mammals. Par3 also regulates barrier function and cell division orientation.

The recent work started with two separate approaches. One of the first authors, Martim Dias Gomes, said: ‘We realized that inactivating Par3 leads to failures in cell divisions, resulting in DNA damage responses.’ At the same time, his colleague and co-first author Soriba Letzian was working on another project: ‘We challenged mouse skin with UV light – but observed an unexpected DNA damage response already in absence of the harmful light, when Par3 was missing. That was the moment we realized that the DNA damage response and the aberrant cell divisions might be tightly linked,’ he said. Based on these results, they teamed up and together examined possible causes of these mitotic failures.

As they now show, Par3 is an important regulator of contractility of keratinocytes, which is required to maintain the accuracy of cell division events. The absence of Par3 led to mitotic errors, causing an alert signal and a cascade of DNA damage responses that then fuelled premature differentiation, and potentially the skin stem cell decline. These findings were surprising, as during the development of epithelial tissues Par3 was considered to serve tissue function rather through orienting mitotic spindles.

These new findings thus revealed that core polarity proteins like Par3 steer mechanochemical networks essential to keep a healthy self-renewal capacity. ‘We are glad that we were able to contribute a piece of the puzzle of how the skin epithelium is maintained intact, and hope that this will serve future medical applications,’ Sandra Iden concludes.

The post Skin in balance: Joint forces of polarity and cell mechanics appeared first on MyMedicPlus.