Cancer excess after arsenic exposure from contaminated milk powder

Abstract

Objectives Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality. Methods We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/ kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals. Results Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent. Conclusions Although dilution is present in these cohortbased data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

Pancreatic cancer risk and levels of trace elements

“…Regarding its association with pancreatic cancer risk, little has been published. However, a potential relation between childhood exposure to milk powder contaminated with arsenic and an almost twofold excess mortality due to pancreatic cancer was recently reported 7 8. Some studies on the relationship between arsenic exposure and type 2 diabetes, which is a potential risk factor for pancreatic cancer, obtained conflicting results 22 23.…”

“…High levels of cadmium have been associated with an increased risk of EPC 5 6. Recently, a potential link between pancreatic cancer mortality and childhood exposure to milk powder contaminated with arsenic has also been suggested 7 8. The objective of the present study was to assess the risk of EPC associated with concentrations of selected trace elements measured in toenails.…”

Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

“…7 In Japan, a cohort study in Okayama Prefecture of infants that were potentially exposed to high levels of arsenic from contaminated milk powder had significantly higher cancer mortality rates compared with infants born in the same area 1 to 5 y after the contaminated infant formula was recalled. 8 Finally, in Bangladesh, a prospective cohort study reported that infants who were exposed to higher levels of arsenic in utero had a greater risk of infectious diseases in the first year of life compared with infants with lower arsenic exposure. 9 While it is not fully understood how early life exposure to arsenic would lead to increased susceptibility to disease later in life, experimental studies have shown that in utero exposure to arsenic alters DNA methylation in offspring.…”

Height and blood chemistry in adults with a history of developmental arsenic poisoning from contaminated milk powder

“…While chronic arsenic exposure is associated with an increased diabetes incidence (Maull et al 2012), this disease is apparently less likely to be triggered by early-life exposure to arsenic. On the other hand, this conclusion must remain tentative at this point, as the population examined represents survivors that may not reveal the full range of adverse effects induced by arsenic poisoning in infancy (Dakeishi et al 2006;Yorifuji et al 2011). …”

“…Approximately 13,000 children were affected and manifested skin pigmentation, diarrhea, and fever; more than 100 died from acute poisoning (Hamamoto 1957). Unfortunately, long-term follow-up studies of the victims have not been carried out, and the absence accessible registries hampers any follow-up studies (Yorifuji et al 2011).…”