Impact of X Chromosome Genes in Explaining the Excess Risk of Cancer in Males

Abstract

The authors examined cancer incidence sex ratios in Denmark for 1943–2003 by age group. At nongenital/nonbreast sites, incidences were consistently higher in males. While environmental factors dominate cancer risk, the authors hypothesized that the higher risk in males might be explained by unspecified X chromosome genes’ protecting female cells from genotoxic damage. If so, cancer susceptibility would be passed from parent to offspring differently by sex. The authors compared relative risks in offspring of parents with and without cancer histories. For all comparisons, relative risks were similar in offspring of fathers with cancer (relative risk (RR) = 1.14, 95% confidence interval: 1.08, 1.20). Risks in offspring were higher for parents diagnosed before age 50 years and for cancers at the same site rather than different sites. Genital cancer risks were increased in same-sex offspring of parents with genital cancers. Breast cancer risks were high in both daughters (RR = 2.37) and sons (RR = 4.63) of mothers with breast cancer and in daughters (RR = 5.96) of fathers with breast cancer. Thus, X chromosome genetic factors were not responsible for the excess risk of cancer in males. Susceptibility to genital cancer was increased in same-sex offspring, and breast cancer risks were increased in both sons and daughters when either parent had had breast cancer.

Keywords: genetics, neoplasms, risk factors, sex factors, sex ratio, X chromosome