What causes esophageal squamous cell carcinoma in a non-smoking, teetotaler female?

From the Guidelines

Esophageal Squamous Cell Carcinoma Causes in a Non-Smoking, Teetotaler Female

The primary cause of esophageal squamous cell carcinoma (OSCC) in a non-smoking, teetotaler female is likely due to genetic predisposition, dietary factors, and recurrent thermal injury 1.

Key Risk Factors

• Genetic predisposition: Inherited genetic variants, such as those found in the PLCE1, TMEM173, and ATP1B2 genes, can increase the risk of OSCC 1.
• Dietary factors: A diet lacking in fruits, vegetables, and dairy products, with low intakes of vitamins A, C, and riboflavin, has been shown to predispose to OSCC 1.
• Recurrent thermal injury: Ingestion of high-temperature beverages, such as tea, may contribute to the development of OSCC 1.
• Low socioeconomic status: OSCC is more common in economically deprived groups and regions 1.

Molecular Characterization

The molecular progression from dysplasia to invasive OSCC involves dysregulation of TP53 and cell cycle regulators, which may be detected in precursor lesions 1. Abnormal P53 protein accumulation has been demonstrated in oesophagitis adjacent to dysplasia and carcinoma 1.

Prevention

Public health education programs should encourage a diet rich in fruits and vegetables, with up to five servings per day, to reduce the risk of OSCC 1. Additionally, reduction in gastro-oesophageal reflux may be achieved by suppressing gastric secretion pharmacologically or by surgery, although its effect on reducing the risk of OSCC is not yet fully understood 1.

From the Research

Risk Factors for Esophageal Squamous Cell Carcinoma

• Older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) are independently associated with the occurrence of ESCCs in non-drinker, non-smoker females 2
• Genetic factors, such as CDKN2A driver alterations, are more frequent in non-drinker, non-smoker females with ESCC, while KMT2D alterations are less frequent 2
• Other potential risk factors for ESCC include:
  • Dietary and nutrition factors 3
  • Gastric atrophy 3
  • Infection and microbiome 3
  • Metabolic factors 3
  • Epidemiological and environmental factors 3
  • Rare diseases such as Fanconi anemia, lichen planus, and tylosis 4

Clinicopathological Characteristics

• ESCC lesions in non-drinker, non-smoker females are predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, and the aspect ratio of the lesion >2 (vertical/horizontal) 2
• Endoscopic keratinization is a common feature of ESCC lesions in non-drinker, non-smoker females 2

Global Incidence and Mortality

• Esophageal squamous cell carcinoma is a major cause of cancer-related morbidity and mortality worldwide, with high incidence rates in Central and Southeast Asia, Eastern and Southern Africa, and South America 5, 6
• Despite a slight decrease in global incidence, ESCC remains a significant public health concern, with 456,000 incident cases each year 6