The WHG Weekly Brief: Issue 2

Stay informed. Stay ahead. Weekly clinical insights.

June 30, 2025 • Estimated Reading Time: 5 minutes

🌟 Editor's Note

Hello!

We are standing at a pivotal moment in medicine, where artificial intelligence is no longer a futuristic concept—it’s an active participant in clinical care. From AI-powered scribes that document patient encounters to algorithms that help detect cancer, the promise of these tools is undeniable. But so is the responsibility to ensure they are safe, explainable, and grounded in evidence. As clinicians, researchers, and innovators, we must approach AI not as a replacement for medical judgment, but as a partner—one that earns our trust through transparency, validation, and ethical design. This issue explores the expanding role of AI in healthcare, and what it means for the future of patient care, clinical decision-making, and professional accountability.

— The WHG Team

A major study published in Nature Medicine has identified nearly 200 genetic loci associated with female reproductive health conditions by analyzing genomic data from over 290,000 women in Estonia and Finland. Researchers found novel risk variants linked to conditions like PCOS, endometriosis, and intrahepatic cholestasis of pregnancy (ICP), many of which had never been studied in this context. Several genes, such as WNT4 and CHEK2, were shown to influence multiple disorders, revealing shared genetic pathways. A new polygenic risk score for ICP demonstrated strong predictive power and was validated in an independent Norwegian cohort. The findings highlight the complexity of reproductive health, showing that many small-effect genetic variants contribute to disease susceptibility. This research could pave the way for personalized risk assessments and earlier, more targeted interventions in women’s healthcare.

✅ The American Medical Association has adopted a new policy calling for greater transparency and oversight of AI tools used in clinical care. The policy emphasizes that AI systems must be explainable—meaning physicians should be able to understand how an algorithm arrived at its conclusions. It also calls for independent third-party evaluation, rather than relying on claims made by developers. Importantly, the AMA states that explainability should not replace traditional safety standards like clinical trials. The policy pushes back against the use of intellectual property as a reason to withhold transparency, especially when patient decisions are at stake. Overall, the goal is to ensure AI supports—not undermines—clinical judgment and patient trust.

🧠 What’s new in research?

June 2025

A study of 121 individuals (ages 18–49) with germline CDH1 pathogenic variants found that 50% reported their diagnosis affected family planning. Nearly 47% faced psychosocial or economic barriers to reproduction, and 12% delayed pregnancy to prioritize cancer risk management (e.g., prophylactic total gastrectomy (PTG) or mastectomy).

Women reported more guilt about passing on the mutation than men. Among those who became pregnant post-PTG, most experienced micronutrient deficiencies and worsening post-gastrectomy symptoms, despite appropriate supplementation. Still, 90% of infants were full-term, and no fetal complications were observed.

🔍 Takeaway: CDH1 carriers face complex reproductive challenges, but healthy pregnancy is possible post-PTG with coordinated care from maternal-fetal medicine and nutrition teams.

June 2025

A cross-sectional survey of 216 Australian patients undergoing genome-wide non-invasive prenatal testing (gwNIPT) revealed that:

  • 74% were referred by a medical doctor

  • 41% received only 5 minutes of pre-screening counseling

  • While most parents showed strong interest in all anomaly types (including those of uncertain significance), only 38% knew they were undergoing genome-wide screening

  • Respondents generally did not understand the variation in accuracy across different anomaly types (p = 0.715)

🔍 Takeaway: Parents want as much genetic information as possible from NIPT, but awareness of what gwNIPT includes — and its limitations — is low.
Pre-test counseling must be strengthened to support truly informed decision-making.

🧬 Gene of the week: CDH1

Primary Breast Cancer + Gastric Cancer

CDH1 (Cadherin-1) is a tumor suppressor gene that encodes E-cadherin, a protein essential for maintaining cell-to-cell adhesion in epithelial tissue. Inherited mutations in CDH1 are most strongly associated with hereditary diffuse gastric cancer (HDGC) and invasive lobular breast cancer (ILC). Individuals with pathogenic CDH1 variants face significantly elevated risks of both cancers, often without a strong family history.

CDH1-related ILC is typically estrogen receptor positive, but may be missed on screening mammography due to its diffuse growth pattern — making MRI-based surveillance critical. Preventive options, including risk-reducing mastectomy and prophylactic total gastrectomy, may be recommended depending on family history.

Because of its dual cancer risk, CDH1 is increasingly included in multi-gene panels for patients with a personal or family history of lobular breast cancer or diffuse gastric cancer.

Absolute risk: A woman with a pathogenic CDH1 mutation has a 39% to 55% lifetime risk of developing lobular breast cancer.

Till next time,

The WHG Team