Epidermal growth factor receptor variants in patients from Myanmar with lung adenocarcinoma

Of the 40 cases of adenocarcinoma of the lung, EGFR sequence variants were detected in 15 accounting for 38%. To date, EGFR variant status has been determined in 151 studies worldwide. There is substantial variation between studies even when grouped by geographical region. The Asia-Pacific NSCLC/adenocarcinoma subgroup had the highest frequency of EGFR variation (47%) and the lowest occurred in the Oceania NSCLC/adenocarcinoma subgroup (12%). Among our neighboring countries, EGFR variant frequency was found to be 48% in China, 45% in Japan, 54% in Thailand, 64% in Vietnam, 52% in Philippines, and 45% in Malaysia [10]. The highest frequency was seen in Vietnam (64%) and lowest in Singapore (40%). The overall frequency was 47%. These figures in the Asia-Pacific countries appear consistent with the frequency detected in our patients from Myanmar. The high frequency in these Asia-Pacific countries highlights the need for EGFR testing in all patients with NSCLC/adenocarcinoma. In Europe, the frequency is much lower, e.g., 15% in France, 12% in the UK, and 15% overall. In North America, the frequency is 22%. The frequency in the Indian subcontinent (26%) was also found to be lower than it was in Myanmar. In Africa, the frequency is 21% [10].

The most frequent variant types found in this study were exon 19 deletion and exon 21 L858 R substitution each accounting for 6 cases (40%). This finding was similar to that in a study in mainland China that found the most common variants to be exon 19 deletion and L858R substitutions [11]. In that study, EGFR variant frequency was 50%. A similar finding was reported by Li et al. in which 71% of patients had exon 19 deletions and 29% had exon L858R substitutions [12]. In Japan, Kobayashi et al. found exon 19 deletion (43%) and L858R substitutions (30.5%) as the most prevalent variant types [13]. These 2 variants account for about 90% of all EGFR variants in NSCLC. Screening for these variants in patients with NSCLC can be used to predict which patients will respond to EGFR-TKIs. Different types of EGFR variants may lead to different levels of tyrosine activation and associate with different oncogenic potential. Common EGFR variants that are found at high frequencies such as L858R substitution and exon deletions, as in our study, might be more oncogenic and thus highly selected for therapy [14].

One case of exon 20 S7681 insertion was found in our study. There were also cases of double variation, i.e., 1 case of exon 21 L858R and exon 18 G719X, and 1 case of exon 20 S7681 and exon 18 G719X. Both cases of double variants in our study were in female patients. In a study in China, double variants were also found to be more common in female patients [15]. The oncogenic potential of the less common variants and double variants is largely unknown, and there is a suggestion that these types confer resistance to therapy such as gefitinib [14].

In our patients with EGFR variants, 5 (26%) were male and 10 (48%) were female. The difference was not statistically significant, but, in the present study, variants were more common in female than male patients. This finding is consistent with the literature reports of high EGFR variant frequency in Asian women. In Japan, EGFR variants were more frequently observed in female patients (76.3%) [16]. In the regions where data were available, EGFR variant frequency in NSCLC/adenocarcinoma is higher in women than men: Europe 22% vs. 9%; Asia-Pacific 60% vs. 37%; Indian subcontinent 31% vs. 23%; Africa 48% vs. 8%; and North America 28% vs. 19%. Only in Bangladesh, is the frequency higher in men (26% vs. 14%) [10].

EGFR variants were most frequently seen in those aged ≤40 years, but we found no significant association with age. Cancer of the lung in general occurs most often between ages 40 and 70 years, with a peak incidence in people in their 50s or 60s. Only 2% of all cases appear before the age of 40 years. It is noteworthy that EGFR variants tend to occur around this younger age.

There were altogether 38 patients from the Bamar ethnic group with cases of adenocarcinoma and EGFR variants were seen in 15 (39%). There were 2 patients with Kayin ethnicity and they showed no EGFR variants.

There was a higher frequency of EGFR variants in never-smokers and ex-smokers, and EGFR variants were not detected in regular smokers from our group. This is consistent with a systemic review [10], which found that EGFR variant frequency is higher in never-smokers compared with ever-smokers: Europe 35% vs. 8%; Asia-Pacific 64% vs. 33%; Indian subcontinent 32% vs. 17%; Africa 41% vs. 6%; and North America 28% vs. 19%. However, in Bangladesh and Taiwan, EGFR variation was slightly higher in ever smokers compared with nonsmokers (24% vs. 22% in Bangladesh and 57% vs. 53% in Taiwan). There was also no significant association between nonexposure to chemicals or dust and EGFR variants. In the present study, EGFR variants were detected in 14 of 31 patients with adenocarcinoma of the lung (45%) who were not exposed to chemicals.

Limitations of our study include the limitations of the EGFR Mutation Test [9] and the small sample size compared with other studies. The logical validity of χ² tests is limited by sample size. Nevertheless, we were able to obtain sufficient data to present a preliminary study of EGFR variant status in patients from Myanmar.

Adenocarcinoma dominates the histological types of lung cancer of the patients from Myanmar whom we tested. EGFR sequence variants were detected in 38% cases, and among them 80% had exon 19 or 21 variants, 7% had an exon 20 insertion, and 13% had compound variants. There were more female than male patients with EGFR variants, but we found no significant association in the small sample size included in the present study. A significant association was found between never-smokers and EGFR variants. Knowledge of EGFR variant status in patients from Myanmar is encouraging for their effective cancer treatment. Further studies are warranted to support clinicians to reduce the mortality and morbidity of patients with lung cancer that remains a major health concern in Myanmar.