OS Disparity, Driver Gene Variations by Race and Ethnicity Seen in CRC

Racial and ethnic disparities in overall survival (OS) persist in colorectal cancer (CRC), according to a study published in JAMA Oncology.¹ These disparities were greatest in patients with metastatic disease, and socioeconomic factors had the largest contribution to these disparities.

CRC is the second leading cause of cancer death worldwide.² Previous studies have demonstrated an association between poor OS and race, with Black individuals having a worse OS and 5-year survival compared with their White, Hispanic, and Asian counterparts. Targeted therapies are usually used for CRC, but variations in KRAS, BRAF, and NRAS, which are more common in Black patients, have made treatment response less predictable.

The study aimed to find and analyze the differences in molecular, socioeconomic status (SES), and clinical factors in the context of racial and ethnic groups. Disparities in OS by race and ethnicity was also investigated to determine the relative association of each covariable.¹

The Foundry software system was used to collect data from January 1, 1973, to March 1, 2023, about patients who had a histologically confirmed colorectal adenocarcinoma. All data were collected from the MD Anderson electronic health records and Cancer Registry. All patients included were Asian, Black, Hispanic, or White, as other racial groups had low numbers in the database.

Racial and ethnic disparities affect overall survival in patients with colorectal cancer | Image credit: Sebastian Kaulitzki - stock.adobe.com

The Area Deprivation Index (ADI) was used to determine the ranking of neighborhood groups by SES using ZIP codes. All neighborhoods were considered either micro- or metropolitan areas, with micropolitan areas those with less than 50,000 residents. Kaplan-Meier analyses stratified to 5-year time periods were used to investigate the temporal change in OS differences. The MD Anderson pharmacy databases were used to collect details on chemotherapy administration. OS was defined as time between diagnosis and death, with the most recent follow-up censored.

There were 47,178 patients included in this study, of which 43.4% were women with a median (IQR) age of 57.0 (17.0) years at diagnosis. The majority of the participants were White (79.4%), followed by Hispanic (8.8%), Black (8.7%), and Asian (3.0%) participants.

Racial disparities were found for OS, with Black patients having a significantly shorter OS compared with White patients (median, 73 vs 62 months; HR, 1.16; 95% CI, 1.09-1.24). OS was longer in both Asian (median, 148 months; HR, 0.66; 95% CI, 0.59-0.74) and Hispanic patients (median, 89 months; HR, 0.86; 95% CI, 0.81-0.92) had longer OS compared with White patients. All stages of CRC had significant differences in OS when assessed along racial and ethnic groups. The median OS was 64, 32, 45, and 40 months for Asian, Black, Hispanic, and White patients with stage 4 disease, respectively.

Metastatic CRC was found in 41% of Black patients compared with 38% of Hispanic, 35% of Asian, and 37% of White patients. Early onset CRC had the highest rate of occurrence in Asian patients (37%) compared with Hispanic (34%), Black (28%), and White (25%) patients. Black patients also had the worst performance status at diagnosis. Black and Hispanic patients made up the largest percentage of patients living in deprived neighborhood quintiles at 43% and 36%, respectively.

Black patients had more frequent variations of APC (OR, 1.40; 95% CI, 1.11-1.76), KRAS (OR, 1.70; 95% CI, 1.42-1.95), and PIK3CA (OR, 1.41; 95% CI, 1.14-1.75) compared with White patients. However, they had less frequent variations on BRAF (OR, 0.35; 95% CI, 1.14-1.75), and KIT (OR, 0.30; 95% CI, 0.14-0.66) compared with White patients. More frequent variation of TP53 (OR, 1.37; 95% CI, 1.01-1.87) was seen in Asian patients.

There were some limitations to this study. Patients who identified as Native American/Alaska Native or Hawaiian or other Pacific Islander were not included due to a small sample size. All participants self-reported their race and ethnicity, which could have failed to capture genetic heterogeneity. The study was also limited to 15 CRC driver genes because clinical targeted sequencing was used to capture racial and ethnic differences. Health insurance and alcohol or tobacco use were not accounted for in the analysis. The study was also conducted at a single center, which could limit generalizability. The median age at diagnosis skewed younger than the national average.

The results of the study confirm that there are still substantial racial and ethnic disparities when it comes to OS among patients living with CRC, the authors concluded. Patients with metastatic CRC had the highest disparities not associated with the stage of the disease. Future strategies on addressing CRC through interventions can be formulated using this data.

References

1. Yousef M, Yousef A, Chowdhury S, et al. Molecular, socioeconomic, and clinical factors affecting racial and ethnic disparities in colorectal cancer survival. JAMA Oncol. Published online September 12, 2024. doi:10.1001/jamaoncol.2024.3666
2. Colorectal cancer: key facts. World Health Organization. July 11, 2023. Accessed September 16, 2024. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer