Zinc dipropionate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment Used in risk assessment for ZnO

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Zinc supplement use and risk of prostate cancer

Author:

Leitzmann MF, Stampfe MJ, Wu K, Colditz GA, Willett WC & Giovannucci EL

Year:

2003

Bibliographic source:

J. Nat. Can. Inst. 95(13): 1004-1007

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was conducted to determine the relationship between supplemental zinc intake and prostate cancer risk among the participants in the Health Professionals Follow-Up Study.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Zinc

EC Number:

231-175-3

EC Name:

Zinc

Cas Number:

7440-66-6

Molecular formula:

Zn

IUPAC Name:

zinc

Constituent 2

Reference substance name:

Reference substance 001

Details on test material:

- Name of test material (as cited in study report): Zinc

Method

Type of population:

general

Ethical approval:

confirmed, but no further information available

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study): High zinc intakes may be positively associated with prostate cancer risk


METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other: - Dietary intake was assessed in 1986 with the use of a 131-item semiquantitative food-frequency questionnaire

- Details: Requested detailed information on the amount and duration of supplement use, including questions on the brand of multivitamin used and the use of vitamins A, C, and E, zinc, iron, and calcium. The Pearson correlation coefficient between zinc intake reported in this questionnaire and in two 1-week dietary records was 0.71, indicating reasonable validity of the questionnaire-based assessment of zinc intake.

- On each follow-up questionnaire, participants were asked to report whether they had been diagnosed with prostate cancer during the previous 2 years.
- Requested permission from men who reported a prostate cancer diagnosis (or from the next of kin for decedents) to obtain medical records and pathology reports, which were used to confirm the diagnosis and to determine the stage of the cases of prostate cancer.



STUDY PERIOD: Study was initiated in 1986, a 14-year follow up was done in the study


SETTING: Harvard School of Public Health


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 51,529 U.S. male health professionals
- Selection criteria: Family history of prostate cancer, age, body mass index, history of type II diabetes, smoking habits, physical activity and dietary intake of nutrients
- Total number of subjects participating in study: 46,974
- Sex/age/race: Male, aged 40-75 years
- Smoker/nonsmoker: Exact number not specified
- Total number of subjects at end of study: 46,974


HEALTH EFFECTS STUDIED
- Disease(s): Risk of cancer in prostate was studied

Details on exposure:

- Dietary supplementation: Among the men in study population, supplemental zinc provided 32% of total zinc intake and thus represented by far the major source of zinc. Other sources of zinc included beef and breakfast cereals, which provided 11% and 5%, respectively, of zinc intake. The median value of the highest category of supplemental zinc intake (reported by approximately 1% of the study population) was 143 mg/day.

- Exposure levels: 0, 10, 44, 82 and 143 mg/d for 35,121, 7,479, 3,117, 845 and 412 participants, respectively

Statistical methods:

Cox proportional hazards model was used for computing multivariable relative risks (RRs). All statistical tests were two-sided.

Results and discussion

Results:

- Compared with nonusers, men who consumed supplemental zinc also consumed more multivitamins, supplemental calcium, supplemental vitamin E, lycopene, copper, iron, folate, and fish, but had lower intakes of red meat, and were slightly less likely to have had a history of prostate specific
antigen screening.
- Non significant associations were found between supplemental zinc intakes at doses less than or equal to 100 mg/d and the risk of prostate cancer- Compared to nonusers, men who consumed more than 100 mg/d of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; P trend = .003)
- Men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; Ptrend <.001).

Confounding factors:

Residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use cannot be ruled out, so the finding that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation.

Strengths and weaknesses:

Not reported

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Supplemental zinc intake at doses of up to 100 mg/d was not associated with prostate cancer risk. However, excessively high supplemental zinc intake may be associated with an increased risk of advanced prostate cancer.

Executive summary:

A study was conducted to determine the relationship between supplemental zinc intake and prostate cancer risk among the participants in the Health Professionals Follow-Up Study. The study was approved by the institutional review board on the use of human subjects in research of the Harvard School of Public Health.   Follow-Up study was initiated in 51,529 male health professionals aged 40 to 75 years and follow-up questionnaires mailed biennially to cohort members to update information on newly diagnosed illnesses.Dietary intake was assessed with the use of a 131-item semi quantitative food-frequency questionnaire. Supplemental zinc provided 32% of total zinc intake representing the major source of zinc.   Compared with nonusers, men who consumed supplemental zinc also consumed more multivitamins, supplemental calcium, supplemental vitamin E, lycopene, copper, iron, folate, and fish, but had lower intakes of red meat, and were slightly less likely to have had a history of prostate specific antigen screening. Non significant associations between supplemental zinc intakes at doses less than or equal to 100 mg/d and the risk of prostate cancer. However, compared with nonusers, men who consumed more than 100 mg/d of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; Ptrend = .003), and men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; Ptrend <.001).Residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use cannot be ruled out, so the finding that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation. Supplemental zinc intake at doses of up to 100 mg/d was not associated with prostate cancer risk. However, excessively high supplemental zinc intake may be associated with an increased risk of advanced prostate cancer.