Abstract

Dietary exposure to 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) in cooked meats maybe responsible for the high burden of Esophageal squamous cell carcinoma (ESCC) in southwestern Uganda.We conducted a pilot case-control study among 31 histologically confirmed ESCC cases and 54 age, gender, and residence matched healthy community controls sampled from the general population at the time of accrual of each case in southwestern Uganda. We collected data including smoking, alcohol consumption, diet, and scalp hair samples analyzed for normalized PhlP (adjusted per gram of melanin). We used logistic regression to determine the association of PhlP and ESCC.Overall, the mean normalized PhIP (ng/g melanin) was 44.79 (SD 148.08), higher among women compared to men (130.68 vs. 9.00, p = 0.03), lowest among healthy men [8.31 (SD 8.52) ng/g melanin] and highest among healthy women 158.39 (SD 288.75) ng/g melanin.In fully adjusted models, covariates associated with greater odds of ESCC included ever smoking 2 to 3 pack years of cigarettes (aOR 7.75 (95% CI 1.90, 31.50) and those 3 or more pack years (aOR5.82, 95%CI 1.25, 27.11), drinking 3 to 4 alcoholic drinks daily (aOR8.00, 95%CI 2.31, 27.74), and normalized PhIP above 75th percentile (8.65 ng/g of melanin) (aOR4.27, 95%CI 1.12, 16.24).In conclusion, high PhIP levels maybe associated with ESCC in a rural Uganda, a high ESCC burden setting. Further study with larger sample with a wider geographical representation is needed to validate scalp hair PhIP for assessment of ESCC risk.

Highlights

  • In Asia and East Africa where Esophageal Squamous Cell Carcinoma (ESCC) - a subtype of esophageal cancer that accounts for at least 80 % of all global esophageal cancers [1,2,3] - is common, known risk factors such as alcohol use and smoking explain just a fraction of disease causation [4,5] compared to high income settings [6,7]

  • Among the 92 samples that were assayed by Liquid Chromatography-Mass Spectrometry (LC-MS), 3 did not have the melanin content measured though crude PhIP levels were assayed

  • There was an increase in the odds of ESCC with 3 to 4 drinks of alcohol daily (Table 3 model 3). This is the first human study reporting an increased risk of ESCC associated with higher scalp hair 2-amino-1-methyl- 6-phenylimidazo [4,5-b] pyridine (PhIP) levels

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Summary

Introduction

In Asia and East Africa where Esophageal Squamous Cell Carcinoma (ESCC) - a subtype of esophageal cancer that accounts for at least 80 % of all global esophageal cancers [1,2,3] - is common, known risk factors such as alcohol use and smoking explain just a fraction of disease causation [4,5] compared to high income settings [6,7]. For other cancers of the breast, colorectum, and prostate, there is conflicting epidemiological evidence with some studies reporting an increased risk with consumption of welldone cooked meat [11,12], and others have shown no associations [10,13,14]. This uncertainty is partly due to the reliance on self-reports of diet which are prone to measurement error in addition to the recall bias and an inability to disentangle effects from other dietary and lifestyle factors

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