Category: Research

MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1

Our study has shown that while the genetic predisposition for many early onset ovarian cancers is still unknown, MSH2 is the most important EOC predisposition gene at age <35 years.

The cumulative likelihood of an EOC in MSH2 heterozygotes would appear to be >2% by 35, with this likelihood still below 0.5% for BRCA1 and rare for BRCA2; indeed, two-thirds of cases identified in BRCA2carriers may not have been driven by HRD.

This increased incidence despite the good long-term survival in MSH2 should prompt awareness of the increased risk and consideration for early risk-reduction strategies.

(Flaum N, Crosbie EJ, Woodward ER, et al MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1 Journal of Medical Genetics  Published Online First: 09 March 2023. doi: 10.1136/jmg-2022-109055)

https://jmg.bmj.com/content/early/2023/03/08/jmg-2022-109055.share

Priorities for Research in Psycho oncology

“We are hosting a workshop to identify priorities for research in #psychooncology across Ireland. This will ensure our research is responsive to the needs and priorities of the Irish cancer community.”

Let us know what you think. https://nuigalwaybusiness.fra1.qualtrics.com/…/SV…

Womb Cancer Genomics – Research and Patient Benefit

Peaches Womb Cancer Trust is proud to present part one of their womb cancer genomics webinar. Originally aired in November 2022.

With Dr Neil Ryan, who shares his wealth of expertise in Lynch Syndrome.

Note: Can be viewed on You Tube

For more information on the topics discussed, please visit:

https://peachestrust.org/

https://peachestrust.org/peaches-pati…

https://www.lynch-syndrome-uk.org/

https://www.genomicsengland.co.uk/

Immunotherapy and… Nothing Else? Studies Test Potential Paradigm Shift in Cancer Treatment

The leaders of those trials and other experts stressed that much more research is needed before this treatment approach becomes part of everyday cancer care. But they agreed that the findings so far are highly encouraging.

The most recent results come from a 35-patient clinical trial conducted at MD Anderson Cancer Center. Most patients in the trial had locally advanced colorectal cancer. Perhaps most important, however, was that all participants’ tumors had specific genetic changes—known as MSI-high or dMMR—that make them particularly good candidates for immunotherapy.

https://www.cancer.gov/news-events/cancer-currents-blog/2023/neoadjuvant-immunotherapy-only-treatment?cid=eb_govdel&fbclid=IwAR26afNcex5ZbX6ocR6wmUfu-rD1T-Ieys82znoFWEYqjvrxOPu1YoigZB0

Harvard Model Identifies Women at High-Risk For Endometrial Cancer

Endometrial cancer is the most common form of uterine cancer and the fourth most frequent cancer diagnosis in women throughout the United States. A new study shines a light on recognizing high-risk individuals.

Key takeaways:

  • Endometrial cancer is the most common gynecological malignancy in the U.S., with mortality rates on the rise.
  • New research has produced a model that identifies those at increased risk of acquiring endometrial cancer.
  • Individuals with Lynch syndrome are more at risk of developing endometrial cancer.

https://healthnews.com/news/harvard-model-identifies-women-at-high-risk-for-endometrial-cancer/

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender(2021)

Results

Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome‐associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided.

Conclusion

The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.

https://academic.oup.com/bjs/article/108/5/484/6287132?login=false

thisisGO – Lynch Syndrome

thisisGO.ie is an online personalised resource for you and yours who have been impacted by a gynaecological cancer.

Also an excellent resource for Lynch Syndrome.

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MyLynch: A Patient-Facing Clinical Decision Support Tool for Genetically-Guided Personalised Medicine in Lynch Syndrome

Lynch syndrome (LS) is associated with varying cancer risks depending on which of the five causative genes harbors a pathogenic variant; however, lifestyle and medical interventions provide options to lower those risks.

“We developed MyLynch, a patient-facing clinical decision support (CDS) web application that applies genetically-guided personalized medicine (GPM) for individuals with LS. MyLynch informs LS patients of their personal cancer risks, educates patients on relevant interventions, and provides patients with adjusted risk estimates depending on the interventions they choose to pursue. MyLynch can improve risk communication between patients and providers while also encouraging communication among relatives with the goal of increasing cascade testing. As genetic panel testing becomes more widely available, GPM will play an increasingly important role in patient care, and CDS tools offer patients and providers tailored information to inform decision-making. MyLynch provides personalised cancer risk estimates and interventions to lower these risks for patients with LS.”

https://www.mdpi.com/2072-6694/15/2/391

“The MyLynch risk estimates and their clinical utility should be validated on larger samples of patients in future studies. We also plan to produce a mobile compatible version of the app as well as incorporate risk uncertainty into the estimates.”

Trials Test Vaccines for Prevention or Delay of Cancers Associated with Lynch Syndrome

Researchers have recruited the first vaccine candidates to one of two new prevention trials that seek to immunize high-risk individuals against Lynch syndrome, the most common cause of hereditary colorectal cancer. Individuals who inherit the condition have an estimated lifetime risk as high as 80% for developing one of these malignancies, as well as an above-average risk for cancers arising in other organs, often at an early age, and regardless of race or gender.

The Nous-209 vaccine—named partially for the number of neoantigens or “new” antigens it contains, and in part for the Switzerland-based company (Nouscom) that developed it—employs what investigators call “a brute force” approach. The vaccine contains 209 bits and pieces of cancer-specific neoantigens expressed only in premalignant or malignant tissues of individuals with Lynch syndrome that researchers hope will stimulate a robust immune-system attack that stops cancer progression at its origin.

In comparison, the Tri-Ad5 vaccines, developed through the National Cancer Institute’s (NCI’s) intramural program, rely on three tumor-associated antigens that are overexpressed in cancer cells, but are also found to a lesser degree in healthy tissues. Because early studies suggested that the approach with only the MUC-1 antigen showed promise, investigators added two other antigens (CEA and brachyury) in the Tri-Ad5 vaccines, which will be combined with an Interleukin-15 (IL-15) “superagonist,” a vaccine stimulant, to increase the vaccine’s potential for destroying premalignant lesions or early tumors.

 “Right now, we are focused on helping high-risk populations, and they, in turn, are teaching us how to develop better cancer preventive vaccines for the future.”

https://prevention.cancer.gov/news-and-events/blog/trials-test-vaccines?fbclid=IwAR2tAZ9dnoQG5wV9sqQG7IkCS-xn0c7er5BbdKrEdlhX3OcCnKDYCyU3Gko#.Y-UkYVtB9fY.facebook