Zinc Supplements in Lowering Cadmium Levels in Smokers

OBJECTIVES:

- Determine whether zinc supplements reduce cadmium levels in smokers.

- Measure serum levels of cotinine (a biomarker of smoking), zinc (a marker of
compliance), and cadmium (the dependent variable) at 3 pre-supplementation visits and
at 6 supplementation visits.

- Determine whether serum cadmium levels (adjusted for serum levels of cotinine) decrease
during supplementation with VisiVite Smoker's Formula.

- Determine if increased cadmium levels in the blood of cigarette smokers can be
correlated with decreased mismatch repair.

- Determine if administration of zinc-containing supplements reverses cadmium-induced
inhibition of mismatch repair.

OUTLINE: This is an open-label, nonrandomized study.

Patients receive oral zinc supplements once daily for 12 weeks in the absence of
unacceptable toxicity.

Blood, serum, and urine are collected once weekly for 3 weeks before beginning treatment and
in weeks 5, 6, 9, 12, 15, and 17 for biomarker/laboratory analysis. Samples are examined for
cadmium, zinc, and cotinine levels by atomic absorption spectrophotometry, expression of
mismatch repair proteins (MSH2, MSH6, MSH3, MLH1, and PMS2), levels of messenger RNA by
reverse transcriptase-polymerase chain reaction, and microsatellite instability by gel
electrophoresis.

After completion of study therapy, patients are followed for 5 weeks.

DISEASE CHARACTERISTICS:

- Currently smoking ≥ 1 pack (20 cigarettes) per day

- Baseline cadmium level ≥ 0.5 μg/L

PATIENT CHARACTERISTICS:

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known gastrointestinal upset due to zinc vitamins or lozenges

PRIOR CONCURRENT THERAPY:

- At least 2 weeks since prior and no other concurrent vitamins and zinc supplements