SERUM AUTO ANTIBODIES RECOGNIZING 5-HYDROXYMETHYL-2'-DEOXYURIDINE, ANOXIDIZED DNA-BASE, AS BIOMARKERS OF CANCER RISK IN WOMEN

Human sera contain anti-5-hydroxymethyl-2'deoxyuridine (HMdU; an oxidi zed thymidine) autoantibodies (aAbs), which are significantly higher i n chronic inflammatory diseases, The intent of this study was to estab lish whether anti-HMdU aAbs can serve as predictors of breast and colo rectal cancer risk, Sera of 169 women were analyzed by ELISA, Women he althy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMd U aAbs over the age-matched controls (P = 0.028 and P < 0.001, respect ively). Subjects diagnosed with rectal cancer had the highest levels o f anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.0 3 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers, Indivi duals with benign breast disease also had elevated anti-HMdU aAb (35.1 2 +/- 8.77; n = 10), with a borderline statistical significance (P = 0 .095), whereas those with benign gastrointestinal tract diseases had t hose 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 t he controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral diseas e) 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 s tability over a period of 6 years, with a low (14%) intraindividual va riance, Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise he althy women who had a family history of breast cancer; in those who ha d benign breast disease or benign gastrointestinal tract diseases; and , most importantly, in those who at 0.5-6 years after the initial bloo d donation developed breast or colorectal cancer.