With summer upon us many are hitting the beach or pool and taking in some rays. Of course we&#8217;re also slathering <img loading="lazy" decoding="async" class="alignright size-medium wp-image-24157" src="https://blog-api.23andme.com/wp-content/uploads/2016/07/Sun-262x300.jpg" alt="Sun" width="262" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2016/07/Sun-262x300.jpg 262w, https://blogcms.23andme.com/wp-content/uploads/2016/07/Sun.jpg 508w" sizes="auto, (max-width: 262px) 100vw, 262px" />on sunscreen, since with sun exposure comes risk for skin cancer.


In the largest-to-date study of the most common form of skin cancer, basal cell carcinoma,  researchers at Stanford University School of Medicine identified 31 genetic associations for the disease, 14 of which were identified for the first time.

<h6>Types of Skin Cancer</h6>

Skin cancer is the most common type of cancer and there are three main types – basal cell carcinoma, squamous cell carcinoma, and melanoma, all named after the affected cell types. Basal cell carcinoma, the most common, affects more than <a href="http://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma">four million people</a> annually in the United States alone – and although it can be disfiguring it is rarely life-threatening.
Squamous cell carcinoma  affects more than <a href="http://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma">one million people</a> annually and leads to about nine thousand deaths each in year in the United States. Melanoma is extremely rare, but it is also deadly.

<h5>Basal Cell Study</h5>
The new basal cell study follows <a href="https://blog.23andme.com/23andme-research/new-genetic-associations-found-for-one-of-the-most-common-skin-cancers/">another recent study</a> by the same group at Stanford that focused on squamous cell carcinoma. Both studies were carried out in a similar two stage fashion. In collaboration with 23andMe, scientists first conducted a large genome-wide association study using 23andMe customers who consented to participate in research and had reported having either basal cell carcinoma or squamous cell carcinoma. Then, a confirmatory genome-wide association study was performed using data from a different cohort of research participants, either from the Nurses’ Health Study or the Health Professionals Follow-Up Study.


Roughly 17,000 cases and nearly 290,000 controls were included in the new basal cell study. The researchers confirmed 17 previously reported genetic associations and identified 14 novel susceptibility regions. Some of the genetic associations are with genes or gene regions thought to regulate skin cells. Other regions are involved in maintaining telomeres – the ends of chromosomes that either become too long or too short in many cancers – regulating the immune system, and tumor progression.
<h6>Other Factors</h6>
The 31 genetic associations identified in this study are estimated to explain almost 11 percent of the familial relative risk for basal cell carcinoma.
Interestingly, many of the regions associated with basal cell carcinoma appeared to exert a bigger effect in younger individuals, which suggested that environmental factors for basal cell carcinoma might become more influential with age. When the scientists tested for interactions between the genetic markers and UV exposure, hair color, number of sunburns, and tanning ability, they found a significant interaction between a genetic marker in a gene called LPP and hair color, specifically light brown and dark brown/black hair groups.
This finding suggests that the LPP marker is exerting a bigger effect on risk for basal cell carcinoma in people with brown or black hair.
Overall, the new basal cell carcinoma study expands our knowledge of the genetic factors that contribute to the most common form of skin cancer. Understanding what drives cancer, both the genetic and environmental factors, and the combination of the two, will ultimately help researchers predict who is at risk, make diagnoses quicker, and develop more precise treatments.


The study appeared in the journal <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992160/" target="_blank" rel="noopener noreferrer">Nature Communications.</a>

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23andMe Blog Team

New genetic variants found to influence risk of most common skin cancer

Using data from 23andMe, researchers at<img loading="lazy" decoding="async" class="alignright size-medium wp-image-2744" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/sun-300x222.jpg" alt="sun" width="300" height="222" /> associated with one of the most common forms of skin cancer, squamous cell carcinoma.


In a study published in <a href="https://www.nature.com/articles/ncomms12048">Nature Communications </a>researchers were able to single out entirely new variants associated with the cancer and they were also able to confirm some previously identified genetic associations. n finding these new associations, the study also uncovered previously unknown biological mechanisms that trigger this form of squamous cell carcinoma.
“Given the large-scale and novel findings of this study, we anticipate that it will be well-received by the scientific community,” said Kavita Sarin, M.D. and Ph.D., who is an assistant professor of dermatology at Stanford and a co-author the paper.

The study is also one of the first genome wide association studies ever done for cutaneous squamous cell cancer. In their work the researchers found 11 genetic variants associated with this form of cancer – four of those have never been seen before.
Squamous cell carcinoma is the second most common skin cancer after basal cell carcinoma.
In the United States about 10 percent of those with European ancestry will have some form of squamous cell carcinoma in their lifetime. Men, people with lighter skin, or those living near the equator, are at higher risk for the disease.
The seven previously known associations are all considered low-to-moderate penetrance sequence variants and are in genes or gene regions related to skin pigmentation, red hair and facial pigmentation– MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. The variant that lies near the gene BNC2 has been implicated in skin cancer as well as freckling and age spots.
The four newly identified variants are in genes or gene regions that influence not only pigmentation, but freckling, age-related pigmentation spots, and skin color. Taken together the 11 genetic associations identified in this study are estimated to explain over 18 percent of the familial relative risk for squamous cell carcinoma.


For this study researchers looked at data from about 300,000 individuals. More than 286,000 of those are 23andMe customers who consented to research. Among those individuals, 6,000 reported having had squamous cell carcinoma and another 280,000 individuals said they’d never had the disease and were used as controls. The researchers followed that initial work by conducting a genome-wide association study using data from about 12,000 people involved in Harvard’s<a href="https://www.hsph.harvard.edu/hpfs/"> Nurses’ Health Study and Health Professionals Follow-Up Study</a>.
This second stage of the study allowed the researchers to further confirm their findings.
This study was led by scientists at Stanford University’s School of Medicine’s Department of Dermatology, and it included contributions from scientists at 23andMe, Indiana University, and Harvard Medical School.
The same group – working with researchers at Brown, and at Tianjin Medical University Cancer Hospital and Institute in China – is also working on research into another very common form of skin cancer,  basal cell carcinoma.

New Genetic Associations Found for Common Skin Cancer

<img loading="lazy" decoding="async" class="alignright size-medium wp-image-6638" title="freckles_moles" src="https://blog-api.23andme.com/wp-content/uploads/2010/06/freckles_moles-300x199.jpg" alt="" width="300" height="199" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/06/freckles_moles-300x199.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2010/06/freckles_moles.jpg 425w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Melanoma is a rare but deadly form of skin cancer. Known risk factors include pale skin, large numbers of moles (also known as nevi), and prolonged sun exposure. Nevus count has a strong genetic component and researchers have already identified some genetic variants that influence the trait. In a new study published in <a href="http://www.cell.com/AJHG/abstract/S0002-9297(10)00265-X">American Journal of Human Genetics</a>, an international team of scientists led by David Duffy and Grant Montgomery reports a genetic variant newly associated with nevus count and melanoma risk, but with an interesting twist.
When Duffy’s team examined data from about 2,000 adolescents of European ancestry living in Australia, they found that each copy of a T at variant was associated with a significant increase in numbers of “flat” nevi (the most common type of nevus). When they looked at data from the parents of the adolescents, however, they saw no such effect. In fact, the data suggested that the C version of — not the T version — was associated with higher nevus counts in older people. Comparing these results with data from thousands of individuals from the UK confirmed the differing age-dependent effects of .
To investigate whether also influences risk for melanoma, the researchers analyzed data from approximately 3,500 individuals with melanoma and over 5,000 healthy individuals, all of European ancestry. The C version of was associated with 1.15 times higher odds of disease, but when they restricted the analysis based on the location of the melanoma, the association was only significant for melanomas on the trunk (main torso). Each copy of a C led to about 1.3 times higher odds of truncal melanoma.
The mechanisms connecting to melanoma risk are not yet fully understood. While the T version of has been associated with traits typically considered risk factors for melanoma (pale skin, dark hair, and freckling), this study suggests that the T version actually protects against the disease. The observation of age-dependent effects on nevus counts adds more wrinkles to the story. Duffy and his colleagues posit that individuals with a T at are more likely to develop large numbers of moles early in life, but that these moles tend to disappear with age. More research will be needed to determine the relationship between age-dependent patterns of nevus counts and melanoma risk.

Genetic Variant Contributing to Melanoma Risk has Different Effects on Mole Count Depending on Age

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3220" title="skincancer" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/skincancer.jpg" alt="" width="320" height="211" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/03/skincancer.jpg 320w, https://blogcms.23andme.com/wp-content/uploads/2009/03/skincancer-300x198.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" />
Melanoma, a rare but potentially deadly form of skin cancer, is more common in women under 40 than in men in the same age group.   After age 45, the tables are turned: men are more likely to be diagnosed with melanoma.
Between the ages of 40 and 50 happens to be when many women enter menopause or perimenopause, a time of declining estrogen levels.   This has prompted some researchers to suggest that estrogen exposure may play a part in melanoma risk.
In a report published last week in Clinical Cancer Research, researchers show that a genetic variation previously associated with several other cancers may be the link between estrogen and melanoma in younger women.   The riskier version of the variation increases the odds a woman will be diagnosed with melanoma before age 40 more than fourfold.
“Potentially, we have a genetic test that might identify pre-menopausal women who are at higher risk for melanoma.   And if that’s the case, then we might want to have increased surveillance of those patients including more frequent visits to the doctor, more rigorous teaching of skin self-examination, and other preventive steps,” said Dr. David Polsky, the study’s lead author, in a statement.
In a sample of 227 people with melanoma — 93 women and 134 men — researchers found that women with two Gs at a specific SNP in the MDM2 gene were diagnosed with the disease 13 years earlier than those with GT or TT at this SNP.   In men, there was no effect of on age at diagnosis.
About 52% of women with GG at this SNP were diagnosed with melanoma before age 50 — and 38% between ages 30 and 39.   Only about 22% of women with GT or TT were diagnosed before age 50. Although those figures are dramatic, it is important to remember that the SNP was not shown to affect melanoma risk generally, but the age at which people who do develop it are diagnosed.
Laboratory experiments have shown that the G version of this SNP causes the MDM2 gene to be turned on at higher levels in response to estrogen than the T version.
Higher levels of MDM2 protein may be relevant to melanoma, as well as other cancers, because its role in cells is to regulate a tumor suppressor protein called p53.   More MDM2 means less p53, which in turn can reduce a cell’s protection against turning into a cancer cell.
More research will be needed to confirm that there is an interaction between estrogen and the G version of SNP that affects melanoma risk.   The authors caution that their study was small, lacked information about the menopausal status of the women they studied and did not include a group of people without melanoma for comparison.
More work will also be needed to understand how the MDM2 gene and the protein it encodes affect cancer risk in general.   The G version of SNP has been associated with earlier onset for some cancers, including soft tissue sarcoma, diffuse large B-cell lymphoma, colorectal cancer, ovarian cancer and non-small cell lung cancer in women, and decreased survival in people with stomach and kidney cancer.   But there is evidence for improved survival in women with ovarian cancer who have the G version of this SNP.   Paradoxically, higher levels of the MDM2 protein (as would be expected with the G version of SNP shown to lead to earlier melanoma onset in the current study) have been associated with improved survival for melanoma.

Genetic Variation May Explain Why Young Women Are At Greater Risk For Melanoma Compared to Young Men

<img loading="lazy" decoding="async" class="alignright size-full wp-image-1651" title="skincancer" src="https://blog-api.23andme.com/wp-content/uploads/2008/10/skincancer.jpg" alt="" width="320" height="211" srcset="https://blogcms.23andme.com/wp-content/uploads/2008/10/skincancer.jpg 320w, https://blogcms.23andme.com/wp-content/uploads/2008/10/skincancer-300x198.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" />
Basal cell carcinoma is not only the most common form of skin cancer in the United States — it’s the most <a href="http://www.nlm.nih.gov/medlineplus/ency/article/000824.htm" target="_blank" rel="noopener noreferrer">common cancer overall</a>. Close to a million new cases are diagnosed each year. Luckily, this type of cancer is easily treated and unlikely to spread. It can, however, cause extensive damage to surrounding tissue and bone if it’s not removed.
The biggest risk factor for basal cell carcinoma (BCC), as well as several other types of skin cancer, is sun exposure. People with light skin, hair, and eyes — who have low levels of the protective skin pigment melanin — are at especially increased risk. It’s therefore not surprising that many of the genetic variants associated with skin cancer are also linked to fair pigmentation.
A new study, published online Sunday in <a href="https://dx.doi.org/10.1038/ng.234" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, has identified two SNPs on chromosome 1 that increase the risk of BCC, but are not linked to a person’s coloring.

After studying more than 2,000 people with BCC and close to 36,000 controls from Iceland and Eastern Europe, Stacey et al found that each A at rs7538876 and each G at rs801114 increased the odds of developing BCC 1.28 times over those with two Gs or two Ts, respectively. 
 (23andMe customers can check their data by clicking on the links above that lead to our Browse Raw Data feature)
The authors of the study estimate that about 1.6% of people with European ancestry have two copies of the riskier versions at both of these SNPs, and that these people have 2.98 times the odds of BCC compared to people who have no risky copies.
The researchers then looked at the DNA of people with two other types of skin cancer that, like BCC, are related to sun. But in about 400 people with squamous cell carcinoma and about 2,000 with cutaneous melanoma, they saw no association with the SNPs.
“One unifying theme may be that genes associated with fair pigmentation confer cross-risk of all three skin cancer types because of their roles in protection from the shared risk factor of UV light, whereas the more specifically associated variants may act through different pathways,” the authors write in their report.
To investigate this idea further, the researchers looked to see if the two new BCC-associated SNPs were related to pigmentation at all. In a sample of about 5,000 Icelandic people they found that neither SNP was linked to eye or hair color, nor were either of them linked to a propensity to freckle or sun sensitivity.
“Taken together, these data suggest that the [SNPs] act through pathways other than those related to UV-susceptible pigmentation traits,” the authors write.

Skin Cancer — Page 2

New genetic variants found to influence risk of most common skin cancer

New Genetic Associations Found for Common Skin Cancer

Genetic Variant Contributing to Melanoma Risk has Different Effects on Mole Count Depending on Age

Genetic Variation May Explain Why Young Women Are At Greater Risk For Melanoma Compared to Young Men

Two DNA Variants Linked to Basal Cell Carcinoma, the Most Common Form of Skin Cancer

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