Acrylamide and Glycidamide Hemoglobin Adduct Levels and Breast Cancer Risk in Japanese Women: A Nested Case–Control Study in the JPHC

Abstract

Background: Acrylamide (AA) is classified as “probably carcinogenic to humans (Class 2A)” by the International Agency for Research on Cancer. AA causes cancer owing to its mutagenic and genotoxic metabolite, glycidamide (GA), and its effects on sex hormones. Both AA and GA can interact with hemoglobin to hemoglobin adducts (HbAA and HbGA, respectively), which are considered appropriate biomarkers of internal exposure of AA. However, few epidemiological studies reported an association of HbAA and HbGA with breast cancer (BC). Methods: We conducted a nested case-control study within the Japan Public Health Center-based Prospective Study cohort (125 cases and 250 controls). Cases and controls were categorized into tertiles (Lowest, Middle, and Highest) using the distribution of HbAA or HbGA levels in the control group and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. Results: No association was observed between HbAA (ORHighest vs. Lowest, 1.34, 95% CI, 0.69-2.59), HbGA (ORHighest vs. Lowest, 1.46, 95% CI, 0.79-2.69), their sum HbAA+HbGA (ORHighest vs. Lowest, 1.36, 95% CI, 0.72-2.58) and BC; however, some evidence of positive association was observed between their ratio, HbGA/HbAA, and BC (ORHighest vs. Lowest, 2.19, 95% CI, 1.11-4.31). Conclusions: There was no association between biomarkers of AA and BC. Impact: It is unlikely that AA increases BC risk; however, the association of AA with BC may need to be evaluated, with a focus not only on the absolute amount of HbAA or HbGA but also on HbGA/HbAA and the activity of metabolic genes.

Exposure to environmental chemicals and cancer risk: epidemiological evidence from Japanese studies

“…These findings are in general agreement with recent meta-analyses [94,95]. Meanwhile, we recently measured hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA) in erythrocytes collected from 125 breast cancer cases and 250 controls in a nested case-control study within the JPHC Study [96]. We found no statistically significant positive association for either HbAA or HbGA, but a positive association between HbGA/HbAA ratio and risk of breast cancer.…”

Association between Toothbrushing and Cancer Risk

“…Regarding alcohol consumption, a study of Japanese men found that those who consumed ≥ 46 g and ≥ 69 g of alcohol per day had a respective 40% and 60% higher risk of developing cancer than those who consumed < 23 g of alcohol per day [ 5 ]. Diet, physical activity, and body weight control are suggested as important factors based on epidemiological evidence [ 6 - 9 ]. In Japan, the population-attributable fraction of cancer due to preventable factors is estimated to be about 55% for male and about 30% for female.…”