Tag: genetics

BRCA1, BRCA2, and Associated Cancer Risks and Management for Male Patients

Mary Pat Campbell

Link: https://jamanetwork.com/journals/jamaoncology/article-abstract/2821594

Excerpt:

Importance  Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been a rapid expansion of US Food and Drug Administration–approved targeted cancer therapies, including poly ADP ribose polymerase (PARP) inhibitors, for breast, pancreatic, and prostate cancers associated with BRCA1/2 PVs.

Observations  This narrative review summarized the data that inform cancer risks, targeted cancer therapy options, and guidelines for early cancer detection. It also highlighted areas of emerging research and clinical trial opportunities for male BRCA1/2 PV carriers. These developments, along with the continued relevance to family cancer risk and reproductive options, have informed changes to guideline recommendations for genetic testing and strengthened the case for increased genetic testing for males.

Conclusions and Relevance  Despite increasing clinical actionability for male carriers of BRCA1/2 PVs, far fewer males than female individuals undergo cancer genetic testing. Oncologists, internists, and primary care clinicians should be vigilant about offering appropriate genetic testing to males. Identifying more male carriers of BRCA1/2 PVs will maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer.

Author(s): Heather H. Cheng, MD, PhD1,2; Jeffrey W. Shevach, MD3; Elena Castro, MD, PhD4; et al

JAMA Oncol. 2024;10(9):1272-1281.

doi:10.1001/jamaoncol.2024.2185

Publication Date: July 25, 2024

Publication Site: JAMA Oncology

23 Tidbits About the Human Operating System

Mary Pat Campbell

Link: https://www.linkedin.com/pulse/23-tidbits-human-operating-system-nate-worrell/

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Excerpt:

1- We Aren’t Totally Human – Almost half of the cells in our body don’t come from us. We have a universe of microorganisms, each of which brings their own DNA into the mix. From a BBC report:

“The human genome – the full set of genetic instructions for a human being – is made up of 20,000 instructions called genes.

But add all the genes in our microbiome together and the figure comes out between two and 20 million microbial genes.

Prof Sarkis Mazmanian, a microbiologist from Caltech, argues: “We don’t have just one genome, the genes of our microbiome present essentially a second genome which augment the activity of our own.

“What makes us human is, in my opinion, the combination of our own DNA, plus the DNA of our gut microbes.”

2- We share DNA with Bananas and Copied Viral DNA: Our closest genetic relative is the chimp, but we are connected to dogs and cats and even fruit flies and yes, bananas.

Author(s): Nate Worrell

Publication Date: 1 Jan 2023

Publication Site: Longevity Assistant at LinkedIn

How your DNA may affect whether you get COVID-19 or become gravely ill

Mary Pat Campbell
How your DNA may affect whether you get COVID-19 or become gravely ill

Excerpt:

Some people can blame their DNA for making them more likely to get COVID-19 or becoming severely ill if they get infected.

A study of more than 45,000 people with COVID-19 has uncovered 13 genetic variants linked to an increased risk of infection with SARS-CoV-2 or a higher chance of developing severe illness, researchers report July 8 in Nature. The team includes more than 3,300 researchers in 25 countries.

Some of the variants had been uncovered in previous studies. For instance, researchers again confirmed a genetic link between blood type and the likelihood of getting infected, but don’t know why people with type O blood may be slightly protected. The study also verified that a variant that disables the TYK2 gene raises the risk of critical illness and hospitalization. That variant is known to protect against autoimmune disease, but leaves people more vulnerable to tuberculosis.   

Author(s): Tina Hesman Saey

Publication Date: 8 July 2021

Publication Site: Science News

Excel autocorrect errors still plague genetic research

Mary Pat Campbell

Link: https://cosmosmagazine.com/science/biology/excel-autocorrect-errors-still-plague-genetic-research/

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Excerpt:

Earlier this year we repeated our analysis. This time we expanded it to cover a wider selection of open access journals, anticipating researchers and journals would be taking steps to prevent such errors appearing in their supplementary data files.

We were shocked to find in the period 2014 to 2020 that 3,436 articles, around 31% of our sample, contained gene name errors. It seems the problem has not gone away, and is actually getting worse.

Author(s): Mark Ziemann, Deakin University and Mandhri Abeysooriya, Deakin University

Publication Date: 27 August 2021

Publication Site: Cosmos magazine

The Science Suggests a Wuhan Lab Leak

Mary Pat Campbell

Link: https://www.wsj.com/articles/the-science-suggests-a-wuhan-lab-leak-11622995184

Excerpt:

In gain-of-function research, a microbiologist can increase the lethality of a coronavirus enormously by splicing a special sequence into its genome at a prime location. Doing this leaves no trace of manipulation. But it alters the virus spike protein, rendering it easier for the virus to inject genetic material into the victim cell. Since 1992 there have been at least 11 separate experiments adding a special sequence to the same location. The end result has always been supercharged viruses.

A genome is a blueprint for the factory of a cell to make proteins. The language is made up of three-letter “words,” 64 in total, that represent the 20 different amino acids. For example, there are six different words for the amino acid arginine, the one that is often used in supercharging viruses. Every cell has a different preference for which word it likes to use most.

In the case of the gain-of-function supercharge, other sequences could have been spliced into this same site. Instead of a CGG-CGG (known as “double CGG”) that tells the protein factory to make two arginine amino acids in a row, you’ll obtain equal lethality by splicing any one of 35 of the other two-word combinations for double arginine. If the insertion takes place naturally, say through recombination, then one of those 35 other sequences is far more likely to appear; CGG is rarely used in the class of coronaviruses that can recombine with CoV-2.

In fact, in the entire class of coronaviruses that includes CoV-2, the CGG-CGG combination has never been found naturally. That means the common method of viruses picking up new skills, called recombination, cannot operate here. A virus simply cannot pick up a sequence from another virus if that sequence isn’t present in any other virus.

Author(s): Steven Quay, Richard Muller

Publication Date: 6 June 2021

Publication Site: Wall Street Journal

A Primer on Insurance Policies and Genetics

Mary Pat Campbell

Link: https://www.soa.org/resources/research-reports/2021/primer-ins-policies-genetics/

Full report: https://www.soa.org/globalassets/assets/files/resources/research-report/2021/primer-ins-policies-genetics-report.pdf

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Excerpt:

A new subset of Somatic non-blueprint information is the growing field of Epigenetics, defined as changes ‘above
the genetics,’ where it has recently been found that lifestyle choices also induce non-heritable physical or chemical
changes directly on a person’s DNA after birth, and can be measured by isolating the DNA and revealing these
features. The U.S. Center for Disease Control states: “Epigenetics is the study of how your behaviors and
environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes
are reversible and do not change your DNA sequence.” (9)


An example of the latter is a finding that the tips of our chromosomes – called telomeres – can shorten or lengthen
in correlation with health status and ‘biological aging,’ a finding that was the subject of a 2009 Nobel Prize (10). An
additional example of epigenetics is in tobacco use, shown below, and generally discussed at the 2020 SOA Health
Conference by Dr. Brian Chen at this link https://webcasts.soa.org/products/actuarial-innovation-and-technologyupdate-on-recent-research#tab-product_tab_speaker_s.

Author(s): James Timmins

Publication Date: March 2021

Publication Site: Society of Actuaries