Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women

Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU nabs (44.80 ± 11.50; n = 6) in comparison to colon (29.03 ± 2.49; n = 33) and breast (35.86 ± 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 ± 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 ± 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 ± 2.86; n = 55) did not significantly differ from those of the controls (19.41 ± 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 ± 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and <0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5- 6 years after the initial blood donation developed breast or colorectal cancer.