Abstract
Background/Objectives: Background: The International Agency for Research on Cancer has classified arsenic as a group 1 carcinogen of the lung, skin and bladder. Arsenic has been implicated in the pathogenesis of breast, prostate, and colorectal cancers; however, existing evidence is limited and inconsistent. Prospective studies, particularly those employing blood-based quantification of arsenic, remain scarce. This study aimed to address this gap by investigating the association between serum arsenic levels and breast, prostate, and colorectal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC) Heidelberg case-cohort. Methods: Serum arsenic levels were measured using inductively coupled mass spectrometry in 5360 participants aged 35-65 years, recruited between 1994 and 1998. Over a median follow-up of 18 years (IQR: 17-19), 685 incident cases of breast, 597 of prostate, and 284 of colorectal cancer occurred. Prentice-weighted Cox proportional hazards regression models with age as the underlying time scale were used to estimate hazard ratios and confidence intervals for associations between serum arsenic levels and cancer risk. Results: No statistically significant association was found between serum arsenic levels and breast cancer, either overall with HR 1.04 (95% Cl: 0.96-1.35) or in subgroups based on pre- and post-menopausal status, estrogen/progesterone status, or BMI. Similarly, serum arsenic levels were not statistically associated with prostate cancer of HR 0.91 (95% Cl: 0.72-1.14). In contrast, a significant association with colon cancer emerged in the second quartile with HR 0.12 (95% Cl: 0.02-0.61) and third quartile with HR 0.19 (95% Cl: 0.05-0.73) compared to the first quartile but not in rectal cancer. Conclusions: More comparative studies on the different arsenic media and arsenic speciation should be conducted to determine the impact of arsenic on these cancers.