KCA-funded research shows how family genetics impact kidney cancer

I’m excited to highlight a new study spearheaded by Dr. Ritesh Kotecha from Memorial Sloan Kettering Cancer Center that describes how renal cell carcinoma (RCC) patients’ genetic ancestry (GA) – which is the information about people who are biologically related – is correlated with clinical, histological, and molecular data across different ancestral groups.

A better understanding of these population-level genetics might reveal new patterns about who RCC affects and what kinds of treatment and survival outcomes these individuals may have.

Dr. Kotecha received a KCA Young Investigator Award in 2020 that allowed him to complete this research. The study, published in the journal Cancer, is called “Genomic ancestry in kidney cancer: Correlations with clinical and molecular features.”

The Challenge of Health Disparities in Kidney Cancer:

Kidney cancer has long shown its varying impacts across different racial and ethnic groups. While socioeconomic factors undeniably play a role, there’s a growing belief that genetic ancestry might offer deeper insights into these disparities. Dr. Kotecha’s research is a beacon in this direction, aiming to unravel these genetic determinants and their implications for disease biology and treatment.

The Study:

Dr. Kotecha and his research collaborators embarked on a comprehensive analysis of 953 kidney cancer patients. The study used both self-reported race and GA classification methods to determine the race category of patients. The GA classification provided a more detailed and accurate representation of the patients’ genetic background, which was crucial for the study’s objectives. They meticulously correlated their genetic ancestry with a plethora of data points, including clinical, histologic, and molecular data. This endeavor stands tall as the largest study of its kind, intertwining genetic ancestry with a rich tapestry of clinical and molecular data.

Key Findings:

The study revealed that the majority of the participants, about 78%, were of European ancestry. Other ancestries, such as African, East Asian, South Asian, and Native American, made up the remainder. Intriguingly, patients of African ancestry often had different types of kidney cancer, presented with more advanced stages of the disease, and unfortunately, had worse outcomes compared to their European ancestry counterparts. This was evident in the survival rates, where African ancestry patients had a median survival of 2.5 years compared to 5.7 years for European ancestry patients.

On the genetic front, differences in genetic profiles were observed based on ancestry. African ancestry patients, for instance, showed fewer of the common kidney cancer-associated gene alterations but had a higher frequency of certain other mutations. Further, using data from The Cancer Genome Atlas, the study discerned that kidney tumors from African ancestry patients exhibited distinct gene activation patterns, which could have profound implications for treatment.

Study Limitations:

While the study is a treasure trove of insights, it’s paramount to acknowledge its boundaries. The majority of participants were of European ancestry, emphasizing the pressing need for more diverse and inclusive research. Being conducted at a single institution, the research might be influenced by referral and geographic biases, which could affect the diversity and heterogeneity of the cohort. Additionally, nonbiological factors, such as socioeconomic status, could play a role in the disparities observed in health care outcomes. Lastly, the study’s reliance on existing reference genomes for calculating GA categories means that incorporating more diverse reference genomes in the future might refine the insights further.

Implications and Future Directions:

These revelations underscore the importance of considering GA in kidney cancer care. Recognizing these genetic nuances can pave the way for more tailored treatment strategies, ensuring better outcomes for patients. The Kidney Cancer Association is proud to have funded this research and remains steadfast in its commitment to support top-notch studies through its grant program.

You can access Dr. Kotecha’s full research article here.