Etiological study of esophageal cancer in Chinese population – With special reference to dietary factors and genetic polymorphisms

  • Topic:
  • Institution: The Chinese University of Hong Kong
  • Country: Hong Kong
  • Status: Completed

Scientific abstract

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Background

Aetiology of esophageal squamous cell carcinoma (ESCC) has not been clearly documented. This study was conducted to identify etiological factors for ESCC in Chinese population and examine the interactions among environmental factors and/or genetic polymorphisms on ESCC susceptibility.

Methods

A population-based case-control study was carried out in Yanting County, which is one of the several areas in China with the highest risk of ESCC. A total of 942 incident ESCC cases aged between 40 and 70 years old with pathological confirmation were recruited; meanwhile, 942 sex and age-matched controls were selected from the local residents by using a multi-stage sampling method. A semi-quantitative food frequency questionnaire (FFQ) was developed and used to collect detailed dietary data. In addition, a structured questionnaire was administered to collect data on:

  1. Basic demographic characteristics
  2. Family cancer history
  3. Detailed smoking and alcohol drinking habits, and tea drinking habits

Furthermore, genomic DNA was isolated from blood cells and extracted by using phenol-chloroform method. A total of 1771 DNA samples were obtained and successfully genotyped with Sequenom genotyping method, reaching an overall call rate > 95% for 93 loci on 41 candidate genes. Logistical regression was applied to assess the associations between individual factors and ESCC and odds ratios (OR) and 95% CI were derived, while other relevant covariates or confounding factors were adjusted. Principle component factor analysis was adopted to derive dietary patterns based on individual food items.

Data on single nucleoid polymorphisms (SNP) for each locus was managed and analyzed by PLINK 1.9. Possible interactions among/between environmental factors and genetic polymorphisms were examined by estimating synergy index (SI) and by including main effects of variables and their product term in the logistical regression models.

Results

Both cases and controls had a mean age of 60 years old, and 71% of them were males. The food items that were found to be associated with an increased risk included salt processed foods, (such as salted meat, pickled vegetables, salted eggs), staple foods including corn and tubecrops. In addition, fast eating habit, preference to fried, hot and spicy food, and hot tea drinking significantly increased the risk of ESCC. More intakes of fresh vegetables, fruits, fresh meat, soy products and nuts were related to a lower risk. Consistently with the individual food items, the prudent pattern and vegetable-fruit pattern were associated with a decreased risk, while the processed food pattern and alcohol drinking pattern were associated with an increased risk.

Alcohol drinking, tobacco smoking were confirmed to be strong risk factors for ESCC. Moreover, the two factors were found to interact with salted meat intake, showing a significant synergic effect on ESCC. SNPs on genes of MTHFR, GSTT1, GSTM1, ADH7, CHRNA6, IGF, PLCE1, and RANKL were significantly associated with the individual’s susceptibility to ESCC. In the interaction analyses, consumption of fresh vegetables/fruits and alcohol drinking were found to modify the effects of genetic polymorphisms of MTHFR, ALDH2, and GSTP1 on ESCC. In addition, statistical epistasis of several loci on different genes possibly modified the individual’s susceptibility.

The study suggested that multi-factors, including dietary factors, individual behaviors and genetic polymorphisms, and their complicated interactions might all involve in the development of ESCC. Education and advocating changes in dietary habits and individual lifestyles are of importance to effectively reduce the risk of ESCC.

Plain language abstract

Background

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is a very common cancer in developing countries including China. However, what cause this cancer have not been clearly known yet. This study was conducted to identify modifiable factors and genetic predisportion to ESCC in a Chinese population and examine possible interactions among the different factors on ESCC.

Methods

The study was conducted in Yanting County, which is one of the areas with the highest risk of ESCC in China. The study subjects were 942 newly diagnosed ESCC cases aged between 40 and 70 years old, 942 sex- and age-matched controls selected from the area. A semi-quantitative food frequency questionnaire (FFQ) was used to collect detailed dietary data from the subjects. In addition, a structured questionnaire was administered to collect data including basic demographic characteristics, family cancer history, detailed smoking and alcohol drinking habits, and tea drinking habits. Furthermore, blood samples were drawn to extract DNA (a genetic material), and analyze genotypes. Data analysis focused on assessing the associations between different variables of interest and ESCC by using multivaritate models where relevant confounding factors were adjusted. In addition, dietary patterns based on individual food items were derived by using principle component factor analysis to see whether and which dietary pattern(s) was/were related to the risk of ESCC.

Key findings

Both cases and controls had a mean age of 60 years old, and 71% of them were males. The food items that were found to be associated with an increased risk included salt processed foods, (such as salted meat, pickled vegetables, salted eggs), staple foods including corn and tubecrops. In addition, fast eating habit, preference to fried, hot and spicy food, and hot tea drinking significantly increased the risk of ESCC. More intakes of fresh vegetables, fruits, fresh meat, soy products and nuts were found to be protective against ESCC. Consistently with the individual food items, the prudent pattern and vegetable-fruit pattern were associated with a decreased risk, while the processed food pattern and alcohol drinking pattern were associated with an increased risk. Alcohol drinking, tobacco smoking were confirmed to be strong risk factors for ESCC. Moreover, the two factors were found to enhance the effect of salted meat intake on ESCC.

Genetic variations on several genes (MTHFR, GSTT1, GSTM1, ADH7, CHRNA6, IGF, PLCE1, and RANKL) were found to be significantly associated with the individual’s susceptibility to ESCC. Consumption of fresh vegetables/fruits and alcohol drinking were found to change the effects of genetic variations of MTHFR, ALDH2, and GSTP1 on ESCC. In addition, different genetic variations on several genes possibly affected each other on the individual’s susceptibility to ESCC.

Conclusions

The study suggests that multi-factors, including dietary factors, individual behaviours and genetic variations, and their complex interactions may all involve in the development of ESCC. Therefore, education and advocating of changes in dietary habits and individual behaviours/lifestyles may be important and effective to reduce the risk of ESCC.

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