Lung cancer Genetic and Racial Disparities

 2.3. Genetic and Racial

 Disparities and Lung Cancer Susceptibility

Lung cancer risk is influenced significantly by

 different racial and ethnic disparities.

 Individuals with African ancestry (AA) have

 higher mortality rates and incidence of lung cancer development at an earlier age compared to individuals with European ancestry (EA) due to disparities in preventive screening monitoring and treatment disparities [39,40].

 In addition, there is a significant disparity in the metabolic pathways and how the body processes nicotine between AA and EA groups, as AA has lower levels of cotinine glucuronidation [41]. 

Non-Hispanic AA males show the highest rates of mortality and lung cancer incidence compared to all race-ethnicities [42,43]. 

Similarly, Primm et al. showed persistent disparities in NSCLC incidence between AA and EA men [44]. 

Interestingly, despite disparities in diagnosis and treatment, AA and Asian NSCLC patients demonstrate better outcomes for the same-stage cancer compared to EA patients [45].

 The cause for disparities is genetic ancestry, as AA populations with LUSC have more genomic instability and aggressive molecular traits, while AA patients with LUAD have a higher frequency of PTPRT and JAK2 gene mutations [46,47].

 Additionally, the Asian population demonstrates a higher frequency of STK11, TP53, and EGFR gene mutation [48],

 but they have longer survival rates and higher chemotherapy responses in comparison to EA patients [49]. 

Ok Another study linked TP53, KRAS, and KEAP1 gene mutations with worse overall survival, whereas EGFR gene mutations are associated with a higher chance of survival [50].

Recent studies found that EA patients have higher mortality rates compared to Hispanics and Asians, and they have a higher susceptibility to lung cancer due to higher frequencies in smoking-related loci [51,52].

 Many studies have revealed racial disparities in the genetic mutation profile of lung cancer patients. Compared to Japanese patients, EA-LUSC patients present a higher frequency of mutations in TP53, PIK3CA, KEAP1, and NFE2L2 genes [53]. 

On the contrary, EA-LUAD patients exhibit a significantly lower occurrence of EGFR mutation but an increased frequency of mutation in the PIK3CA, KEAP1, KRAS, TP53, BRAF, NF1, STK11, RBM10, and MET genes.

 Weiner and Winn reported a higher prevalence

 of EGFR gene mutation in the East Asian population and more predominant KRAS and STK11 gene alterations in EA and AA populations [54]. 

Generally, the disparities in survival rates between EA and AA populations are noticeable in patients who are young and have localized tumors [55].

 The disparities also exist in histological subtype, stage, and tumor grade. Asian or Pacific Islander (API) exhibit a higher frequency of adenocarcinoma (ADC) compared to AA, EA, and American Indian/Alaska Native (AIAN) patients [56].

Ref

International Journal of Molecular Sciences logo

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur Kratzke