Carcinogenic Interactions For Ingested Arsenic

Numerous factors have been or might be hypothesized to interact with arsenic ingested from drinking water in increasing the risk of, or altering susceptibility to, cancer. Table 4 summarizes these. Below, we review evidence for such effect modifiers.

Genetic Susceptibility: Methylation Capacity

Methylation capacity has been hypothesized to play a role in susceptibility to arsenic-induced carcinogenicity. Hsueh et al. (1997) classified subjects from a Taiwanese study according to the percent of arsenic excreted as monomethyl arsonic acid (MMA) in urine and also by cumulative arsenic exposure. These authors found that the multivariate adjusted odds ratios for skin cancer differed in these four groups. Within the low cumulative arsenic exposure group, those with a higher percentage of urinary MMA showed a relative risk of 3.0 compared to those with a lower percentage (<26.7%). Among those with a low excretion of MMA, a higher cumulative arsenic exposure was associated with an 8-fold increased risk of skin cancer. However, when comparing the highly exposed, high MMA excreters to those with low exposure and low MMA excretion, the OR was 24. These findings suggest that methylation capacity could substantially alter the additive impact of arsenic exposure, i.e., the number of excess cases in a population. Since arsenic exposure was simply dichotomized into low and high cumulative exposures, and since these were fairly high levels, studies are needed with a finer stratification of arsenic exposure and perhaps of methylation capacity. Further data are needed to determine whether these interactive effects are linear or not.

Genetic make-up of a population or individual is likely to modify the carcinogenic effect of arsenic exposure, and methylation capacity is one primary suspect for genetic control. Chiou et al. (1997) present data from Taiwan suggesting that both GST-T1 and GST-M1 may alter methylation capacity. Other data related to possible genetic factors are reported by Hopenhayn-Rich et al. (1996). In a study of Chileans in the Atacama Desert, those of European descent had an increased ratio of excreted MMA : DMA as compared with native populations (Atacamerios) who have lived in the local area for centuries.

Nutritional Factors

Hsueh et al. (1997) report on nutritional status of their study population. They found that in a three-year follow-up, participants with a higher intake of beta-carotene had lower risk

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