Gender differences in chemical carcinogenesis in National Toxicology Program 2-year bioassays

Differences in cancer incidences between men and women are often explained by either differences in environmental exposures or by influences of sex hormones. However, there are few studies on intrinsic gender differences in susceptibility to chemical carcinogens. We have analyzed the National Toxicology Program (NTP) database for sex differences in rat responses to chemical carcinogens. We found that the odds that male rat bioassays were assigned a higher level of evidence than female rat bioassays was 1.69 (p < .001). Of 278 carcinogenic chemicals in the database, 201 (72%) exhibited statistical gender differences (p ≤ .05) in at least one nonreproductive organ. One hundred thirty of these 201 chemicals induced gender-specific tumors in male rats and 59 in female rats. Sixty-eight chemicals induced tumors in males but no tumors in females. Less than one third (i.e., 19 chemicals) induced tumors in females but not males. Male-specific tumors included pancreatic and skin tumors, and female-specific tumors included lung tumors. For some tumor sites, these differences in gender susceptibility can be associated with literature data on sex hormone receptor expression. In conclusion, gender-specific tumors were common. The male dominance is in line with recent human data, and the male susceptibility to carcinogens should be further studied.