Cancer genes in lung cancer: racial disparities: are there any?

Abstract

Cancer is now known as a disease of genomic alterations. Mutational analysis and genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent "oncogenic drivers" in the processes of tumorigenesis and progression. In this review, we will highlight the key driver oncogenic gene mutations and fusions identified in lung cancer. The review will summarize and report the available demographic and clinicopathological data as well as molecular details behind various lung cancer gene alterations in the context of race. We hope to shed some light into the disparities in the incidence of various genetic mutations among lung cancer patients of different racial backgrounds. As molecularly targeted therapy continues to advance in lung cancer, racial differences in specific genetic/genomic alterations can have an important impact in the choices of therapeutics and in our understanding of the drug sensitivity/resistance profile. The most relevant genes in lung cancer described in this review include the following: EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1. Commonly identified genetic/genomic alterations such as missense or nonsense mutations, small insertions or deletions, alternative splicing, and chromosomal fusion rearrangements were discussed. Relevance in current targeted therapeutic drugs was mentioned when appropriate. We also highlighted various targeted therapeutics that are currently under clinical development, such as the MET inhibitors and antibodies. With the advent of next-generation sequencing, the landscape of genomic alterations in lung cancer is expected to be much transformed and detailed in upcoming years. These genomic landscape differences in the context of racial disparities should be emphasized both in tumorigenesis and in drug sensitivity/resistance. It is hoped that such effort will help to diminish racial disparities in lung cancer outcome in the future.

Keywords: cancer gene; lung cancer; racial disparities; targeted therapy.

Figure 1.

Age-specific SEER lung cancer incidence rates in the United States: 2000-2008. Reproduced with permission from the National Cancer Institute‥

Figure 2.

Spectrum of EGFR oncogenic driver mutations among different racial groups with NSCLC. The different color shades represent EGFR mutational rates reported by different studies. Data on the African American and Latin American cohorts are based on a limited number of studies available.^,- Data on the Asian and white cohorts are abundant over recent years, and several representative studies were selected for graphical representation here.^,,,,,,

Figure 3.

Spectrum of oncogenic driver mutations in Asian never smokers with lung adenocarcinoma.^- The data were collected from 3 different studies to represent the mutational frequency range of different genes among the same population. N/A = not available.

Figure 4.

Spectrum of KRAS oncogenic driver mutations among different racial groups with NSCLC. The different color shades represent KRAS mutational rates reported by different studies. Data on the African American and Latin American cohorts are based on a limited number of available studies.^,-, Data on the white cohort are based on multiple studies including 2 meta-analyses of 22 studies with 1,470 NSCLC patients.^,,,- Data on the Asian cohort are based on studies conducted in the Chinese and Korean populations.^-

Figure 5.

Spectrum of MET mutations among different racial groups with NSCLC. The frequency of MET mutations is presented in accordance of the findings with the histological subtypes of lung cancer and racial groups.

Figure 6.

Spectrum of LKB1 oncogenic mutations among different racial groups with NSCLC.^-, The different color shades represent LKB1 mutational rates reported by different studies.

Figure 7.

Spectrum of EML4-ALK oncogenic driver fusions among different racial groups with NSCLC.^,,,,,, The different color shades represent EML4-ALK rates reported by different studies. Data among human populations other than white and Asian are lacking thus far.