Category Archives: Genetics

Genetics

New form of EDS identified by mutation in THBS2 gene – Ehlers-Danlos News

A mutation in the gene THBS2 cause a newly defined form of Ehlers-Danlos syndrome (EDS) thats characterized by unusual flexibility as well as prolonged bleeding and blood vessel abnormalities, a new study reports.

The study, Heterozygous THBS2 pathogenic variant causes EhlersDanlos syndrome with prominent vascular features in humans and mice, was published in the European Journal of Human Genetics.

EDS refers to a group of connective tissue disorders that are typically characterized by symptoms including an abnormal range of joint motion and fragile skin. More than a dozen identified types of EDS exist, however, each with different causes and typical manifestations.

The patient at the center of this study is a woman in her late 20s of Ashkenazi Jewish ancestry who sought medical attention for a history of frequent joint dislocations, tendon rupture, easy bruising, and prolonged bleeding when injured. She also reported fatigue in her legs after exercising.

The patients older sister and their mother reported similar symptoms. Imaging studies showed blood vessel abnormalities: the younger sister and her mother both had unusual pooling of blood in veins in the lower legs; the mother also had abnormalities in a heart valve. Of note, the mothers father, who had a history of aneurysms (bulging or swollen blood vessels) while alive, had died of a blood vessel rupture.

The three women underwent EDS-specific genetic testing, but analyses of more than a dozen genes linked to EDS showed no noteworthy findings. A more widespread analysis identified 43 genetic variants that were in both sisters. Most of these were common in people of Ashkenazi Jewish ancestry and were ruled out, and a few others were ruled out by genetic testing of the extended family.

The researchers then zeroed in on a mutation in the THBS2 gene that was found in both sisters, but not their unaffected relatives or in databases of genetic samples from more than 7,000 Ashkenazi Jews.

Everyone inherits two copies of the THBS2 gene, one from each biological parent. In the sisters, just one copy of the gene carried a mutation (called p.Cys896Arg), indicating that this form of EDS is inherited in an autosomal dominant pattern where one mutated copy is sufficient to cause disease.

Our findings demonstrate that the THBS2 p.Cys896Arg variant has a dominant effect, the researchers wrote.

To confirm that this mutation was disease-causing, the researchers generated mice carrying the same mutation in the mouse version of the THBS2 gene. These mice demonstrated excessive flexibility in fact, the researchers said they were able to tie the mices tails into knots without causing the animals any notable distress. The mice also bled excessively when injured.

Upon lab evaluation of the mices tissue, the researchers noted that collagen fibers were disorganized. Collagen is the main protein that gives body tissue its structural integrity, and collagen abnormalities are a defining feature of EDS.

Altogether, these data define a new form of EDS caused by a mutation in the THBS2 gene. The scientists are working on further studies to understand the biological mechanisms of how THBS2 mutations lead to connective tissue abnormalities.

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New form of EDS identified by mutation in THBS2 gene - Ehlers-Danlos News

Genetics

Genetics of estrogen production linked to endometrial cancer risk in postmenopausal women – News-Medical.Net

In a recent study published in eBioMedicine, researchers determine the genetic regulation of blood estrone levels in postmenopausal women to explore associations between their genetic loci and endometrial cancer.

Study:Genome-wide association study identifies genetic regulation of oestrone concentrations and association with endometrial cancer risk in postmenopausal women. Image Credit: Peakstock / Shutterstock.com

Once a woman has gone through menopause, her ovaries no longer produce estrogens, thereby causing her serum estradiol concentrations to be extremely low or undetectable. In Type 1 estrogen-sensitive endometrial cancer, which accounts for over 80% of all endometrial cancers and predominantly affects menopausal women, estrone, the contributing estrogen, is synthesized in non-ovarian tissues like fat. Following the production of estronein these tissues, this hormone is converted into estradiol, a more potent form of estrogen.

Previous studies have shown that obesity is a significant risk factor for Type 1 endometrial cancer. This association may be attributed to the greater amount of total fat mass that facilitates more estrone production.

Alternatively, various genetic factors may lead to increased estrone production after menopause, thereby contributing to an increased risk of endometrial cancer in these women. In fact, one variant in the CYP19A1 gene, which is involved in the aromatization of testosterone to estradiol, has been positively associated with estradiol concentrations and postmenopausal endometrial cancer.

Importantly, studies investigating the relationship between CYP19A1 variants and endometrial cancer risk have been limited due to their small sample size and lack of sensitive analytical methods.

In the present genome-wide association study (GWAS), researchers quantified blood estrone, testosterone, and dehydroepiandrosterone (DHEA) levels with high precision using liquid chromatography-tandem mass spectrometry (LCMS) to identify single nucleotide polymorphisms (SNPs) associated with sex hormone concentrations. The association between hormone-associated SNPs and endometrial cancer was determined from 205,427 white British females between 39 and 71 years of age, 0.9% of whom were diagnosed with endometrial cancer.

The study also included women 70 and older from the Sex Hormones in Older Women (SHOW) and ASPirin in Reducing Events in the Elderly (ASPREE) studies. Non-fasting blood samples were obtained from these study participants to measure sex hormone concentrations through LCMS.

The final analysis cohort comprised 4,951 postmenopausal women of European descent, with a median age of 73.9. No genome-wide signals were observed for testosterone or DHEA, the latter of which is the precursor for both estrone and testosterone. However, the GWAS identified four independent SNPs for estrone concentrations below the genome-wide significance threshold after adjusting for age and BMI.

These SNPs included rs34670419, which may be involved in transcriptional regulation; rs56400819, which contributes to the DNA damage response; rs2846729, which is mapped to a ribonucleic acid (RNA) gene; and rs2414098, which is mapped to CYP19A1. The SNP with the highest prevalence within this study cohort was rs56400819 at 45% as compared to rs34670419, which had the lowest prevalence in this cohort at 4%.

Lower estrone levels were observed for rs34670419, rs2846729, and rs2414098 carriers compared to rs56400819 carriers, who exhibited higher estrone concentrations. Furthermore, rs2414098 carriers had a significantly lower risk of endometrial cancer after adjusting for age at recruitment, BMI, parity, and history of diabetes.

Previous GWAS on endometrial cancer have primarily focused on estradiol concentrations; however, this hormone often cannot be accurately quantified, particularly among postmenopausal women. Comparatively, the current study examined estrone concentrations, in which a dose-response relationship was observed between the identified SNPs and estrone concentrations.

Importantly, the researchers of the current study limited one of their analyses on rs2414098 to women over 58 years of age in an effort to ensure postmenopausal status. These findings confirm that the impact of this SNP on cancer risk can be attributed to estrone and is independent of the effects of circulating estrogens and progesterone.

The current study highlights the importance of measuring estrone levels, in addition to other sex hormones, in postmenopausal women to determine cancer risk. Some important strengths of this study include the confirmation of postmenopausal women in the study cohort, the large sample size, and the use of LCMS, a highly sensitive and precise analytical instrument.

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Genetics of estrogen production linked to endometrial cancer risk in postmenopausal women - News-Medical.Net

Genetics

Cord Blood Registry (CBR) by CooperSurgical and Fulgent Genetics Launch Innovative Genetic Testing – PR Newswire

Testing offers CBR families the opportunity to proactively seek additional information about their child's health

TRUMBULL, Conn. and EL MONTE, Calif., Feb. 9, 2024 /PRNewswire/ -- CooperSurgical, a global leader in fertility and women's health, and Fulgent Genetics, Inc. (NASDAQ: FLGT), a technology-based company with a well-established clinical diagnostic business and a therapeutic development business, today announced that they have partnered to offer families of Cord Blood Registry (CBR) exclusive newborn genetic screening panels.

"We are proud to offer our CBR families additional resources that complement our newborn stem cell services as we continue to deliver personalized, cutting-edge solutions to families nationwide," said Holly Sheffield, President of CooperSurgical.

Utilizing Fulgent's Picture Genetics platform, CBR, the largest private newborn stem cell preservation company in the world, now offers a range of genetic testing options to its families, including:

"Partnering with CBR allows us to help provide more families with actionable information about their newborn's health," said Brandon Perthuis, Chief Commercial Officer of Fulgent Genetics. "Part of our mission is to use our resources and testing to improve the lives of those around us. Newborn genetic analysis serves as an illustration of this commitment, as early intervention may significantly improve health outcomes for many of these conditions."

These Picture Genetic tests are available now exclusively to CBR clients. All three Picture tests evaluate over 30 genes associated with conditions that are potentially treatable with newborn stem cells as part of a stem cell transplant.1

For more information, please visit http://www.cordblood.com/genetic-testing.

About CBRby CooperSurgical

Cord Blood Registry (CBR) is the largest private newborn stem cell company in the world, helping parents store stem cells from cord blood and cord tissue for their children. Founded in 1994, CBR is the #1 choice for parents1 and most recommended by OB/GYNs for newborn stem cell preservation.2 The company has released over 700 samples intended for use in transplant medicine and regulated investigational regenerative medicine applications.1 CBR is here to help expand the possibilities of what newborn stem cell therapies can do for families and give parents the confidence to Bank on CBR. More information can be found at http://www.cordblood.com.

About CooperSurgical

CooperSurgical is a leading fertility and women's healthcare company dedicated to putting time on the side of women, babies, and families at the healthcare moments that matter most in life. CooperSurgical is at the forefront of delivering innovative assisted reproductive technology and genomic solutions that enhance the work of ART professionals to the benefit of families. We currently offer over 600 clinically relevant medical devices to women's healthcare providers, including testing and treatment options.

CooperSurgical is a wholly-owned subsidiary of CooperCompanies (Nasdaq:COO). CooperSurgical, headquartered inTrumbull, CT, produces and markets a wide array of products and services for use by women's health care clinicians. More information can be found atwww.coopersurgical.com.

About CooperCompanies

CooperCompanies (Nasdaq: COO) is a leading global medical device company focused on improving lives one person at a time. The Company operates through two business units, CooperVision and CooperSurgical. CooperVision is a trusted leader in the contact lens industry, improving the vision of millions of people every day. CooperSurgical is a leading fertility and women's health company dedicated to assisting women, babies, and families at the healthcare moments that matter most. Headquartered in San Ramon, CA, CooperCompanies ("Cooper") has a workforce of more than 15,000 with products sold in over 130 countries. For more information, please visitwww.coopercos.com.

About Picture Genetics

Picture Genetics was launched in 2019 as a service of Fulgent Genetics. Picture Genetics offers consumers direct access to Fulgent's advanced genetic testing and analytics capabilities from the ease and comfort of home, at an affordable price point. With multiple tests available to meet the varying needs of consumers, Picture Genetics provides a holistic approach to at-home genetic screening to complement Fulgent's comprehensive genetic testing analysis. Picture Genetics reports provide medically actionable, clinical-level results with professional medical oversight in one easy process. Visit http://www.picturegenetics.comfor more information.

About Fulgent

Fulgent is a technology-based company with a well-established clinical diagnostic business and a therapeutic development business. Fulgent's clinical diagnostic business offers molecular diagnostic testing services, comprehensive genetic testing, and high-quality anatomic pathology laboratory services designed to provide physicians and patients with clinically actionable diagnostic information to improve the quality of patient care. Fulgent's therapeutic development business is focused on developing drug candidates for treating a broad range of cancers using a novel nanoencapsulation and targeted therapy platform designed to improve the therapeutic window and pharmacokinetic profile of new and existing cancer drugs. The company aims to transform from a genomic diagnostic business into a fully integrated precision medicine company.

References

Contact CooperSurgical EvolveMKD [emailprotected]

Fulgent GeneticsMelanieSoloman, The Blueshirt Group [emailprotected]

SOURCE CooperSurgical

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Cord Blood Registry (CBR) by CooperSurgical and Fulgent Genetics Launch Innovative Genetic Testing - PR Newswire

Genetics

Gene Variant Linked to Lower Levels of Hormonal Birth Control – The Scientist

A genetic variant present in 5 percent of the population is tied to substantially lower blood levels of the active ingredient in a hormonal contraceptive implant, researchers reported this week (March 11) in Obstetrics & Gynecology. Two other, more common genetic variations also correlated with lower levels of the hormone, although not by as much. The authors say the finding may help explain why women taking some oral hormonal contraceptives sometimes get pregnant anyway.

The biggest takeaway is that weve assumed for so long that if a woman taking birth control gets pregnant, then she must have done something wrong, coauthor Aaron Lazorwitz, an obstetrician and gynecologist at the University of Colorado, tells Wired. Instead, maybe we need to pay more attention as physicians to other things that might be going on, like genetics, so we can give better, more individualized treatment to women...

Lazorwitz and his colleagues recruited 350 women using a form of birth control that is implanted under the skin, where it slowly releases the hormone etonogestrel into the bloodstream to suppress ovulation. They tested the womens genes and monitored their blood levels of etonogestrel. People with a mutation that keeps the gene CYP3A7, which breaks down hormones, active into adulthood had lower levels of etonogestrel, on average, than those without the variant. Lower levels of etonogestrel were also associated with higher body mass index, a longer length of time women had been using the implant, and to a lesser extent with variants in the genes NR1I2(PXR) and PGR, which code for steroid receptors.

The risk of unintended pregnancy while on birth control for women who carry the CYP3A7 variant cannot be quantified. Not at this point. It's too early, Lazorwitz tells CNN. He says he doesnt think the variant will affect how well the implant works, but that it could possibly affect the action of oral contraceptives, which put lower levels of hormones into circulation in the body. Theres so much we dont know about birth control. There seem to be things outside of a womans control like genetics that could impact how well birth control works, he says. And we need to start taking those things in consideration.

The study provides a glimpse into the next questions we should be asking as to how we can improve care, Anne Davis, an obstetrician and gynecologist at NewYork-Presbyterian/Columbia University Irving Medical Center who was not involved in the work, tells Reuters. Knowing that there is a difference in how people metabolize hormones sets the stage for more research that can help us understand the experiences of women better and that can help us give the right medication to the right patient.

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Gene Variant Linked to Lower Levels of Hormonal Birth Control - The Scientist

Genetics

CooperSurgical, Fulgent partner on genetic screening panels – Medical Device Network

US-based CooperSurgical has partnered with Fulgent Genetics to provide exclusive newborn genetic screening panels to families of the CBR.

The collaboration leverages Fulgents Picture Genetics platform to offer a suite of genetic testing options through CBR, a private newborn stem cell preservation company and a CooperSurgical brand.

Fulgent Genetics chief commercial officer Brandon Perthuis said: Partnering with CBR allows us to help provide more families with actionable information about their newborns health.

Part of our mission is to use our resources and testing to improve the lives of those around us. Newborn genetic analysis serves as an illustration of this commitment, as early intervention may significantly improve health outcomes for many of these conditions.

The testing options include CBR Snapshot, which screens for more than 250 genes related to various disorders in children where early detection could be crucial.

CBR Portrait expands on this by screening for over 600 genes, including those related to rare conditions.

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The most comprehensive test, CBR Landscape, screens for more than 1,500 genes and includes a pharmacogenetic component to predict medication metabolism and potential adverse reactions.

All these Picture Genetic tests are made available exclusively to CBR clients and evaluate genes associated with conditions potentially treatable with newborn stem cells.

CoperSurgical president Holly Sheffield said: We are proud to offer our CBR families additional resources that complement our newborn stem cell services as we continue to deliver personalised, cutting-edge solutions to families nationwide.

A wholly-owned subsidiary of CooperCompanies, CooperSurgical is engaged in producing and marketing products and services for use by womens health care clinicians.

Last year, CooperCompanies acquired certain medical device assets, focused primarily on Doppler monitoring, obstetrics and gynaecology surgery markets, from Cook Medical.

Give your business an edge with our leading industry insights.

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CooperSurgical, Fulgent partner on genetic screening panels - Medical Device Network

Genetics

UM Today | Faculty of Science | The intersection of genetics and advocacy – UM Today

February 12, 2024

Witta Iruvma is a fourth-year genetics student at the University of Manitoba and UMSU Womens Representative. In this interview with her, we learn about her journey in science, her challenges in the field of genetics, how she hopes the Faculty of Science supports students and her advocacy work for the UMSU Womens Centre and Black Student Empowerment Society.

1. Can you share a key moment from your journey in genetics and what sparked your interest in this field? Were there any specific experiences or classes that shaped your passion for genetics?

My interest in science was sparked from a very young age. I am a very curious person and I loved hands-on learning experiences such as science experiments. When I took my first genetics class at university, I discovered an interest in the intricacies of what sets us apart from each other. The Introduction to Human Genetics course not only deepened my understanding but also further shaped my passion for genetic diseases and exploring potential their treatments.

2. Have you faced any obstacles or unique experiences as an undergraduate student in this field? How have you navigated them?

Like many others, I faced challenges attending university online. Commencing my undergraduate journey virtually proved to be especially difficult, as I struggled to adjust to the new experience without the resources that wouldve been readily available in person. Upon transitioning back to in-person classes, I felt behind in both knowledge and experience. Fortunately, relying on my close circle for support proved helpful in navigating the new spaces. I highly recommend seeking guidance from professors or advisors, as I found their support to be incredibly beneficial.

3. How do you think the department, faculty or university could help remove these barriers and provide support?

The university has a lot of great resources; however, it may be challenging to navigate, especially for new students. I believe it wouldve helped me a lot if key resources were pointed out to me when I first started. It was always great to see them highlighted on UM Learn or incorporated into lecture slides. Additionally, I think it would be nice if your department or faculty suggested some student groups or other relevant student accounts you should stay up to date with. This could alleviate feelings of isolation and foster connections with other students in your program.

4. You are the VP for social media and marketing for the UMSU Womens Centre and on the social media team for Black Student Empowerment Society. How do you actively contribute to fostering equity, diversity and inclusion within these roles?

In my role as UMSU Womens Rep, I advocate and promote gender equity and inclusivity on campus through various initiatives. The Womens Centre plan and host events that celebrate womens achievements and contributions. We often collaborate with other student groups to create intersectional events that address the diverse experiences of women. We raise awareness about gendered based issues through campaigns and discussion sessions. On the black empowerment society, the social media team aims to use our platforms to highlight the diverse narratives of our community. We share resources and events that promote understanding and appreciation of diverse Black cultures.

5. How do your studies intersect with and complement your advocacy and leadership roles?

While advancing in my studies, Ive noticed that theres a lack of representation of Black Women within the field of genetics. Promoting diversity and inclusion goes beyond my official roles, my passion for advocacy extends into the science community as well. I believe that representation of individuals from diverse backgrounds in both health care and research ensures that studies do not overlook marginalized communities.

Kimia Shadkami

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UM Today | Faculty of Science | The intersection of genetics and advocacy - UM Today

Genetics

Secrets of human genetics could optimize medical care – Earth.com

In a study that bridges human evolution and modern medicine, researchers have shed light on the genetic marvels of adaptation among high-altitude populations. The research may ultimately pave the way for innovative approaches in treating respiratory diseases.

The study was led by Dr. Tatum Simonson, founder and co-director of the Center for Physiological Genomics of Low Oxygen at the University of California School of Medicine.

In Dr. Simonsons lab at UC San Diego, her team set out to investigate whether there may be a genetic explanation for why some people with sleep apnea or pulmonary diseases such as chronic obstructive pulmonary disease (COPD) fare better than others.

There are people with COPD who breathe a lot and maintain a higher oxygen saturation. Others with the same disease dont breathe as much, and their oxygen saturation is low, said Dr. Simonson.

Researchers suspect there may be genetic differences underlying this variation, similar to the variation we find in pathways important for oxygen sensing and responses underlying natural selection at high altitude.

The research is centered around the discovery of a genetic variant that is prevalent among certain Andean populations. These individuals possess an extraordinary ability to thrive in the oxygen-scarce environments of high altitudes.

The genetic variant, associated with a lower red blood cell count, stands as a testament to human adaptability, revealing how specific populations have evolved to evade the potentially lethal condition known as excessive erythrocytosis (EE). This condition characterized by an overproduction of red blood cells poses significant risks, including increased blood viscosity that can lead to stroke or heart failure.

The researchers analyzed the regulation of the EPAS1 gene, which is instrumental in managing hemoglobin concentrations and the bodys response to low oxygen levels.

The EPAS1 gene is critical for the survival of mountain-dwelling Tibetans against the adverse effects of high altitudes. It has been inherited from ancestors who intermingled with archaic human populations tens of thousands of years ago.

The team has now identified a distinct mutation within the EPAS1 gene that is exclusive to Andeans. By analyzing Andean genomes, the researchers found that the genetic change which alters only a single amino acid in the protein product happened by chance about 9,000 to 13,000 years ago and spread very quickly through hundreds of generations within the Andean population.

Similar to Tibetans, the EPAS1 gene is associated with lower red blood cell count in Andeans. However, it works in a completely different way. The Andean variant alters the proteins genetic makeup rather than its expression levels.

Tibetans have, in general, an average lower hemoglobin concentration, and their physiology deals with low oxygen in a way that doesnt increase their red blood cells to excessively high levels. Now we have the first signs of evidence that Andeans are also going down that path, involving the same gene, but with a protein-coding change. Evolution has worked in these two populations, on the same gene, but in different ways, said Dr. Simonson.

This discovery not only underscores the diverse evolutionary strategies employed by humans to adapt to extreme environments but also highlights the potential for these genetic insights to inform medical practices. By understanding the mechanisms through which these adaptations occur.

This paper shows one gene associated with one particular phenotype, but we think there are many different genes and components of oxygen transport involved, said Dr. Simonson. Its just one piece of that puzzle, and could provide researchers with information relevant to other populations.

In precision medicine, its important to recognize variation in genetic backgrounds, specifically in historically understudied populations.

If we can find some shared genetic factors in populations in an extreme environment, that may help us understand aspects of health and disease in that group and groups more locally. In that way, this study aims to push research forward, and towards comprehensive personalized medicine approaches in clinics here in San Diego.

The study is published in the journal Science Advances.

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Genetics

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever – Nature.com

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Genetics

Significance of genetic mutations in toxic tort cases – Rhode Island Lawyers Weekly

The primary question in many toxic tort cases is what caused the disease? When defending these cases, one necessarily asks: (1) is the product/substance I am defending capable of causing the disease in question; and (2) was the plaintiff exposed to enough of it to have done so.

With cases involving cancer, particularly mesothelioma, genetic science is adding to the mix and providing information that, in the right case, changes the equation entirely.

Generally, cancer is a genetic disease caused by gene mutations that control how cells grow and multiply (NIH The Genetics of Cancer, 2022). While cells are the bodys building blocks, genes are sections of DNA in each cell that provide instructions to make required proteins and control cell growth. Hundreds of DNA and genetic changes (variants, mutations or alterations) have been discovered that help cancer form, grow and spread.

My experience with these issues arises from the defense of asbestos cases. The principles raised, however, may well apply to other toxic torts involving cancer.

It is now recognized that there are multiple causes for malignant mesothelioma, a number of which are unrelated to asbestos. Diffuse malignant mesotheliomas are variably associated with prior asbestos exposure, and the strength of the association varies with anatomical tumor site, gender and asbestos fiber type.

The relationship between asbestos and mesothelioma has also evolved and shows significant geographic variation. The epidemiological evidence correlating time trends, incidence by gender, and commercial asbestos use indicates that a majority of pleural mesotheliomas in women, and almost all peritoneal mesotheliomas in women and men, in the United States, appear unrelated to asbestos.

If not asbestos, then what was the cause?

In July 2019, many of the worlds foremost experts on the subject detailed the current state-of-the-art knowledge on the development of mesothelioma. See Carbone, et al., Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy, CA Cancer J Clin., 69:402-429 (2019).

Among the co-authors of the publication were preeminent researchers and practitioners from the University of Hawaii Cancer Center, Memorial Sloan Kettering Cancer Center, Rutgers Robert Wood Johnson Medical School, Brigham and Womens Hospital, Mayo Clinic, Icahn School of Medicine at Mount Sinai, and MD Anderson Cancer Center. Under a section of the publication entitled The Role of Genetics, the authors state:

Cancer is caused by the accumulation of genetic damage. Genetic damage can be inherited, can develop spontaneously, can be caused by exposure to carcinogens and oncogenic infectious agents, or can be caused by the interplay of a combination of these factors. Currently, there is a very active debate about the relative contribution of these factors to human cancer . [A] growing percentage of cancers are attributed to inherited mutations of DNA repair genes and of other genes that, when mutated, accelerate the accumulation of DNA damage and/or the percentage of cells carrying DNA damage . These concepts apply to mesothelioma.

In broad strokes, there are two types of genetic cases: (1) cases involving somatic or random genetic mutations; and (2) cases involving a germline genetic mutation.

Somatic random mutations develop because of DNA changes that occur during stem cell divisions. These mutations arise naturally and accumulate as a person ages. Age is a significant risk factor for almost all forms of cancer, including spontaneous or naturally occurring mesothelioma.

The basis for age-induced tumorigenesis relates to the hosts generation of critical driver mutations within cells and the subsequent formation of clonally expanded proliferation of mutated cells to form tumors. Stem cell division occurs continuously and requires a faithful replication of the highly complex genetic information contained within the genome and cell nucleus.

Random mistakes or mutations (replication errors) occur continuously and with increasing frequency over time, with the capacity of the host to efficiently identify and correct such mutations diminishing with age.

Because mutation accumulation occurs spontaneously and continuously over time, the risk of spontaneous or naturally occurring mesothelioma, either pleural or peritoneal, increases continuously with age.

Random mutations account for two-thirds of the risk of getting many types of cancer. In such cases, no exposure to an exogenous agent (such as asbestos or therapeutic radiation) is required for tumor initiation. Replicative mutations can be responsible for either initiating the process or driving tumor progression.

The current best available scientific evidence is that some mesotheliomas are linked to inherited germline mutations. Overall, at least 12 percent of mesotheliomas occur in carriers of germline genetic mutations. These germline genetic-induced mesotheliomas typically occur in persons of younger age and are often peritoneal rather than pleural mesotheliomas.

As the cohorts of asbestos workers vanish due to old age, increasing percentages of mesotheliomas, especially peritoneal mesotheliomas, occur in individuals who are not occupationally exposed to asbestos. These mesotheliomas may be caused by environmental exposure, genetic predisposition or both.

When examining a toxic tort/cancer case, it may not always be the environment or the toxin that is the culprit. If a plaintiff has an appropriate family history of cancer, genetic testing may provide a viable defense. Anthony J. Sbarra, Segal McCambridge

Pathogenic germline mutations of BAP1 and, less frequently, of other tumor suppressor genes have also been detected in approximately 12 percent of patients. This subgroup of genetically linked mesotheliomas occurs in younger individuals who rarely report asbestos exposure, and with a M:F ratio of 1:1 and survival ranging from five to 10 or more years.

While heritable gene mutations can predispose an individual to cancer (i.e., lower the amount of exposure necessary to cause disease), they can also be sufficient to cause cancers, including mesothelioma, in and of themselves.

Put another way, the presence of a heritable germline mutation, absent or independent of extrinsic factors such as asbestos exposure, can be a cause of mesothelioma.

While the import of these findings may be largely self-evident, there are some takeaways worth considering. First, when examining a toxic tort/cancer case, it may not always be the environment or the toxin that is the culprit. If a plaintiff has an appropriate family history of cancer, genetic testing may provide a viable defense.

Second, genetic germline mutations do not automatically turn a plaintiff into an eggshell plaintiff. While that argument may work in some cases, given that the mutation can be independently causative, it should not apply in all of them.

Anthony J. Sbarra is a shareholder at Segal McCambridge in Boston and focuses his practice on product liability and toxic tort cases. He can be contacted at [emailprotected].

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Significance of genetic mutations in toxic tort cases - Rhode Island Lawyers Weekly