skin cancer

Skin cancer risk in red-heads

This is quite interesting to a degree. I mean, we already know there is a strong genetic component to skin cancer, independent of sun-exposure.

Redhead Pigment Boosts Skin-Cancer Risk

From Nature magazine

Fair-skinned, red-haired folks know — sometimes through painful experience — that they are more susceptible to the damaging effects of the Sun’s ultraviolet (UV) rays, including sunburn, skin ageing and a higher risk of skin cancers. But a study published today in Nature suggests that in mice, the pigment responsible for this colouring has a role in the development of melanoma.

“There is something about the redhead genetic background that is behaving in a carcinogenic fashion, independent of UV,” says David Fisher, a cancer biologist at Massachusetts General Hospital in Boston, who led the study. “It means that shielding from UV would not be enough.”

Compared to people with darker skin, those with fair, freckly skin and red hair produce a different form of the pigment melanin. This red–yellow form, called pheomelanin, is less effective at protecting the skin from UV damage than the darker form, eumelanin. The difference is caused by a mutation in the gene MC1R.

But for a number of years there have been hints that UV exposure alone might not account entirely for the risk of melanoma in redheads. Fisher and his team wanted to investigate the molecular backdrop for this increased risk.

The researchers looked at how melanomas develop in mouse models of olive-skinned, ginger and albino colouring. The last group had the same genetic background as the dark-skinned mice but lacked the enzyme needed to synthesize melanin. The researchers also tweaked each group’s genes to be more susceptible to developing benign moles, which Fisher says is a probable first step in the development of melanoma.

No sunlight needed
The researchers planned to expose the mice to UV light and monitor differences in melanoma development. But before they got to that part of the experiment, about half the ginger mice had developed melanomas. Fisher says that he and his team were shocked. “The first thing we needed to do was bring a UV meter into the animal room to be sure there wasn’t some inadvertent UV being radiated out of the light bulbs or something,” he says. “And it turned out there was not.”

The result suggested that the pigment itself was a cause of melanoma. The researchers suggest that the increased melanoma risk could have something to do with the pigment-production process, or a by-product of it, in melanin-containing cells called melanocytes.

Eugene Healy, a clinical dermatologist at the University of Southampton, UK, says that although the mechanism is interesting, it is probably a less common trigger of melanoma than UV radiation. Indeed, in the UK, 8 out of 10 cases of melanoma are due to UV exposure. In humans, most melanomas develop on skin that sees the sun. “You almost never see melanoma, for example, on the buttocks,” says Healy.

To complicate the picture, one of Healy’s own studies, published in 2010, suggested that pheomelanin was protective against the effects of UV radiation in another type of skin cell, the keratinocyte.

The sun-safety message does not change because of the latest results. “UV is very tightly and convincingly linked to the formation of most non-melanoma types of skin cancer,” Fisher says. “One of the most important messages from this is to avoid an assumption that this takes UV off the hook.” It is possible that UV exposure worsens the carcinogenic mechanism of the red pigment, he adds.

Healy is keen to avoid alarming people with fair complexions. “Whatever risk was there, was always there. But we don’t see lots of spontaneous melanomas in redheads. We shouldn’t be sending out a worrying message for them.”

This article is reproduced with permission from the magazine Nature. The article wasfirst published on November 2, 2012.

PDT for Basal Cell Carcinoma: A Long-Term Follow-Up

This was in journal watch. Does anyone use DMSO?



Long-term results show 5-aminolevulinic acid photodynamic therapy to be beneficial for basal cell carcinomas when surgery is not a good option.

Although surgical removal is the mainstay of basal cell carcinoma (BCC) therapy, additional options are desirable in some situations. One alternative is 5-aminolevulinic acid photodynamic therapy (ALA-PDT), but data are scarce concerning which BCC types are amenable to this treatment and long-term outcomes. In this study, investigators treated 60 BCCs in 44 patients with one or two sessions of ALA-PDT and followed them for 10 years. Morpheaform and pigmented BCCs were excluded from treatment, but recurrent lesions were included. The protocol involved debulking of the tumor, treatment with the drug penetration enhancer dimethylsulfoxide (DMSO) for 5 minutes, followed by ALA-PDT. ALA was activated by a broadband light unit with an emission spectrum in the 550–700 nm range.

The 10-year complete response rates were 87% with two treatment sessions and 60% with one session. All recurrences developed within 3 years of treatment. At 10 years, 90% of the primary tumors were recurrence free, but ALA-PDT was effective for only two of the five recurrent tumors. Recurrences were more likely in men. Physician evaluators considered the cosmetic outcome to be excellent or good in 90% of treated sites at 1 year and in 100% at 10 years.

Comment: Long-term results with 5-aminolevulinic acid photodynamic therapy for basal cell carcinomas are very positive — comparable to other nonsurgical interventions. Longer-wavelength light sources in the 625-nm range (as used in this study) are probably the best choice for BCC treatment, because they penetrate more deeply into the skin than shorter-wavelength blue lights. The authors speculate that DMSO may have contributed to efficacy by augmenting conversion of ALA to its active metabolite. Dermatologists may wish to consider ALA-PDT for primary BCCs when surgical procedures should be avoided.

 Craig A. Elmets, MD

Published in Journal Watch Dermatology June 15, 2012


Christensen E et al. High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: A prospective, clinical and histological 10-year follow-up study. Br J Dermatol 2012 Jun; 166:1342.

Basal Cell Carcinoma at a Young Age: Another Consequence of Tanning Beds

Tanning bed users younger than 40 developed early-onset BCCs significantly more often than nonusers.

Over the past 4 decades, the incidence of basal cell carcinoma (BCC) has increased markedly, particularly in women under the age of 40. This increase coincides with the more frequent use by the public of tanning beds for cosmetic purposes. Estimates suggest as many as one third of teenagers in the U.S. have used tanning beds at least once, and 40% regularly use this means of tanning. Although good epidemiological evidence associates tanning bed use with cutaneous squamous cell carcinomas (SCCs) and melanomas, the effect on BCCs has been less certain. Investigators examined the development of BCCs in young tanning bed users.

The researchers compared interview responses by 376 patients with prior history of biopsy-proven BCC and 390 patients with other dermatological conditions (age, <40 in both groups). Men and women who had used indoor tanning beds at least once were significantly more likely than never-users to have early-onset BCC (BCC that develops before age 40; odds ratio, 1.69). The association between tanning bed use and early-onset BCC was greater in women than in men and greater in patients with multiple BCCs than in those with single BCCs. In multivariate analysis, this association grew stronger with increasing years of use. Researchers also identified a strong association between early-onset BCC and having had a tanning bed–induced burn. Compared with nonusers, tanning bed users were nearly four times more likely to have BCCs on the extremities and more than twice as likely to have BCCs on the trunk. Tanning bed users had no observable increase in BCCs on the head and neck, areas subject to considerably more ambient sun exposure. The authors estimated the percentages of early-onset BCCs that could have been prevented by tanning bed avoidance at 27% overall and 43% among women alone.

Comment: Few studies have evaluated the association between tanning bed exposure and basal cell carcinoma, and the results of existing studies are inconclusive because most included older individuals in the study population. This well-designed study was limited to assessment of the under-40 population that is most likely to use tanning beds. The observation that tanning bed use was associated with BCCs of the trunk and extremities highlights the importance of complete examinations of frequent tanning bed users, not only for BCCs but also for melanomas and squamous cell carcinomas of the skin.

 Craig A. Elmets, MD

Published in Journal Watch Dermatology February 3, 2012


Ferrucci LM et al. Indoor tanning and risk of early-onset basal cell carcinoma. J Am Acad Dermatol2011 Dec 8; [e-pub ahead of print]. (


FDA approves vismodegib for basal cell cancers

Hi All

This is very interesting. I am unaware of any other such treatment for BCC.  Although this is only for advanced tumours at this point,  it does point towards new treatment options in the future.




The Food and Drug Administration has approved the groundbreaking, first-in-class drug Erivedge (vismodegib, Genentech) to treat adult patients with advanced and metastatic basal cell cancers.

Cleared under the FDA’s priority review program — which allows an expedited six-month evaluation of drugs that may offer major treatment advances — Erivedge is intended for use in patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and for patients whose cancer has metastatized.

Erivedge is taken in pill form once a day. It works by inhibiting the Hedgehog pathway, which is active in most basal cell cancers and only a few normal tissues, such as hair follicles, according to the FDA website.


See for more about this.

Risk of melanoma with other cancers

Hi All

Happy new year

I found this interesting



Cutaneous Melanoma Risk Higher Among Cancer Survivors
A study published in the December issue of the Archives of Dermatology, one of theJAMA/Archives journals reveals that, cancersurvivors have a higher chance of developing cutaneous melanoma (CM), one of the most aggressive forms of skin cancer. Individuals with previously diagnosed melanoma are at the highest risk.

In the United States, CM is the fifth most commonly diagnosed cancer among men and the seventh among women. The number of CM cases is rising, while mortality rates from the disease have not considerably decreased. UV radiation exposure is the greatest risk factor for the development of CM, although this risk is affected by individuals’ genetics and race.

In order to understand the risk of CM in cancer survivors, Geoffrey B. Yang, B.S., a medical student at Case Western Reserve School of Medicine, Cleveland, Ohio, and his team examined data from the Surveillance, Epidemiology, and End Results database from 1988 to 2007. 70,819 individuals diagnosed with CM as a first primary cancer (median age of 54 years at the time of diagnosis) were included in the investigation, as well as 6,353 cancer survivors with CM (median age 70 years at time of melanoma diagnosis).

The researchers discovered that individuals with a previous melanoma diagnosis were at higher risk of developing melanoma – a discovery consistent with other investigations. Among individuals under 45 years at initial cancer diagnosis, 777 developed cutaneous melanoma.

The risk of developing CM was considerably higher among patients with previous CM, other skin cancer, Kaposi sarcomalymphoma and female breast cancer. Individuals aged 45+ at initial cancer diagnosis had a considerably higher risk of developing CM following first CM diagnosis, other skin cancers, female breast cancer, lymphoma, leukemiaocular melanoma, and prostate cancer.

The researchers explain:
“Characteristics associated with better survival in both cohorts included female sex, age younger than 45 years at melanoma diagnosis, being married, being white vs. black, decreasing Breslow depth [how deeply tumor cells have invaded], lack of tumor ulceration, no nodal involvement, and absence of metastases [the spread of cancer from the primary tumor to other locations in the body.”

They conclude:
“Given that cutaneous melanoma is the most common second primary cancer in patients with first CM (a risk that remains elevated for over 15 years), our results suggest the need for continued skin surveillance in melanoma survivors.”

Protein May Make UV Exposure Safer In Morning – from Scientific American

I found this facsinating.




Levels of a DNA repair protein naturally rise in the morning and fall later in the day, which may make exposure to UV safest early.

The early bird gets the worm—and may avoid skin cancer. Because a new mouse study suggests that, for humans, tanning in the mornings may be less likely to permanently damage DNA and cause skin cancer.

A mouse’s levels of the DNA-repairing protein XPA are different from ours—they peak in the morning and bottom out in the evening. Researchers exposed mice to UV radiation when their XPA was at its minimum level, around 4 a.m., and others to the same rays around 4 p.m., when XPA levels peaked.

Mice who tanned while low on the repair protein developed skin cancer faster and five times more frequently than their evening-tanning counterparts. The study is in the Proceedings of the National Academy of Sciences. [Shobhan Gaddameedhi et al, Control of skin cancer by the circadian rhythm]

Unlike mice, humans are not nocturnal, so their XPA levels rise and fall at different times. In people, XPA is at prime DNA-repairing levels in the morning, which thus looks the safest time for UV exposure. So if you want to avoid skin cancer, probably go to the tanning salon early—or better yet, don’t go at all

Anti-sleeping sickness (trypanosomiasis) drug prevents BCC

Hi All

I found this interesting




An antiparasitic agent used to treat African sleeping sickness was shown to reduce incidence of skin cancer in follow-up results from a phase 3, randomized, double blind, prospective study.

In the original study, 291 men and women with a history of basal cell carcinoma or squamous cell carcinoma were assigned to 500 mg/m2 daily alpha-difluoromethylornithine (DFMO) or a placebo for 4 to 5 years. Researchers observed a significantly reduced incidence of skin cancers associated with DFMO.

In this follow-up study, Howard H. Bailey, MD, professor of medicine with the University of Wisconsin School of Medicine and Public Health, said researchers found that participants assigned to DFMO developed 163 basal cell carcinomas compared with 243 for those assigned to placebo. The annual event rate was 0.28 basal cell carcinomas per person for DFMO vs. 0.4 for placebo (P=.03).

“We found there is still evidence that the men and women assigned to DFMO for 5 years continued to have a lower incidence of nonmelanoma skin cancers compared with people assigned to placebo,” Bailey said in a press release. “What we saw was that the presumed benefit that people got in taking DFMO appeared to persist for years after stopping it.”

The results were presented at the 2011 AACR International Conference on Frontiers in Cancer Prevention Research.

DFMO did not appear to have a similar protective effect against squamous cell carcinoma. Researchers observed 95 squamous cell carcinomas in the DFMO group compared with 115 in the placebo group. Annual event rate for DFMO was 0.15 squamous cell carcinomas per person compared with 0.19 for placebo (P=.56).

DFMO was associated with few adverse events. Some patients developed ototoxicity, but that did not lead to a “noticeable reduction in hearing,” Bailey said.

“Our data suggest that the protective event that we saw in our prospective study appears to continue, and there was no evidence of any rebound effect,” he said. “We did not find any evidence that the people who received DFMO were harmed other than the original ototoxicity

Skin cancer vaccine hope

From the Sun-Hearld

CANCER expert Prof Ian Frazer is on the verge of a major breakthrough in skin cancer – he hopes to develop a vaccine within a year.

The former Australian of the Year and creator of the world’s first cervical cancer vaccine, Gardasil, has developed a world-first strategy to combat the insidious disease that affects two out of three Australians.

“In my lifetime we should be able to remove the threat of skin cancer from the next generation,” the 57-year-old immunology professor said.

“The smoking gun evidence is there is a virus or viruses that cause it.”

Prof Frazer believes people can “catch” cancer from a virus.

He proved his theory by identifying the human papilloma virus (HPV) as the cause of cervical cancer and then developing a vaccine against the virus to rid the female population of the cancer.

Now he is using a similar tactic to try to combat skin cancer, including malignant melanomas.

“This group of cancers caused by virus infection present a great opportunity because the idea of vaccinating to prevent a cancer is enormously appealing,” he said.

Prof Frazer said the problem was two-fold.

“Genetics and variations in people’s immune systems may expose some people to greater risk of skin cancer after sun exposure,” he said.

“If you take away the body’s defence systems, skin cancer becomes more common.”

His theory is that some viruses – particularly the wart virus or HPV – are embedded in the layers of the skin, which then pose a skin cancer risk for people with damaged immune systems.

“The technology now exists for me to test my theory,” Prof Frazer said.

“It is very powerful but also very expensive.

“Using this tool, we will go hunting for the fingerprints of the virus or viruses present.”

Prof Frazer’s team will input all the sequenced genetic information on skin cancer – which will take six months – and then get an answer.

“We will know if a virus causes skin cancer and what virus it is,” he said.


Review of sun-exposure in kids

Hi All

Have a look at this commentary and abstract. Obviously something we knew already. Fascinating the stats about the current risk of melanoma (in USA obviously) vs 1935. I can get you a copy of the article if you would like.

Baby’s Sun Exposure Could Mean Cancer Later.

According to a review in the July issue of Pediatrics, it could be setting a child up for melanoma or other skin cancers later in life. UV radiation can suppress the immune system and damage skin cells – a process that may happen more quickly in babies than in adults, the authors note.

Young skin is delicate and thinner. It produces less melanin, a skin protecting pigment. UV rays can reach the pigment producing melanin cells, called melanocytes, and damage them. Damage to those cells is a “precursor to melanoma,” says Robin Gehris, M.D., the chief of pediatric dermatologic surgery at the Children’s Hospital of Pittsburgh. “Infant skin may be even more prone to sun damage than we had thought, and that might be important later on for melanoma and other cancer risk,” says Gehris, who was not involved in the new review.

Sun exposure earlier in life, from infancy through adolescence, seems to be associated with different cell changes and an earlier diagnosis of melanoma than exposure in the adult years, the article points out. One study cited in the review has projected that 1 in 33 babies born today will develop melanoma during their lives, versus 1 in 1,500 babies born in 1935.

The American Academy of Pediatrics (AAP), which publishesPediatrics, advises parents to keep children 6 months or younger out of the sun completely. For older babies, the AAP recommends dressing infants in brimmed hats and sun-protective clothing, applying sunscreen to any small patches of exposed skin, and minimizing sun exposure during the midday hours, when the sun is at its hottest.

Significance of mitotic rate in melanoma prognosis

Have a look at this abstract which is the importance of mitotic rate (and lack of importance of Clark level)

J Clin Oncol. 2011 Apr 25. [Epub ahead of print]

Prognostic Significance of Mitotic Rate in Localized Primary Cutaneous Melanoma: An Analysis of Patients in the Multi-Institutional American Joint Committee on Cancer Melanoma Staging Database.


Melanoma Institute Australia; and the University of Sydney, Sydney, New South Wales, Australia; University of Pennsylvania, Philadelphia, PA; Memorial Sloan-Kettering Cancer Center, New York, NY; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Michigan, Ann Arbor, MI; John Hopkins Medical Institutions, Baltimore, MD; and University of Alabama at Birmingham, Birmingham, AL.


PURPOSE The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma. METHODS From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available. Results Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm(2) to 48% for those with ≥ 20/mm(2) (P < .001). Mean number of mitoses/mm(2) increased as the primary melanomas became thicker (1.0 for melanomas ≤ 1 mm, 3.5 for 1.01 to 2.0 mm, 7.3 for 3.01 to 4.0 mm, and 9.6 for > 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had ≥ 5 mitoses/mm(2) compared with 16% of nonulcerated melanomas (P < .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (χ(2) = 104.9; P < .001), mitotic rate (χ(2) = 67.0; P < .001), patient age (χ(2) = 48.2; P < .001), ulceration (χ(2) = 46.4; P < .001), anatomic site (χ(2) = 34.6; P < .001), and patient sex (χ(2) = 33.9; P < .001). Clark level of invasion was not an independent predictor of survival (χ(2) = 3.2; P = .37). CONCLUSION A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness.