Case-Control Information

Methods

Study

Subjects

This case-control study was conducted in New York, NY, from 1994 to 1998. Participants have been described in detail elsewhere [17].

Briefly, women >/= 18 yr of age who were US residents and diagnosed with histopathologically confirmed, invasive epithelial ovarian cancer within the past year were recruited from Memorial Sloan-Kettering Cancer Center (n = 122) and New York Hospital (n = 46).

Controls were not population based, since the cases tend to represent a more affluent clientele. As a result, we used a design intended to select controls of similar socioeconomic characteristics. Two types of community controls were obtained.

One type (n = 81) was recruited from the same neighborhood as cases, frequency matched for age, using a standard method of random-digit dialing. The second type (n = 78) was recruited from microneighborhoods defined by Zip + 4 postal codes.

We combined the two community control groups, inasmuch as they were similar in age, race, income, education, and risk factors for ovarian cancer. A third group of "convenience" hospital-based controls (n = 92) was recruited from friends of patients and visitors at the two hospitals. We excluded controls with a history of bilateral oophorectomy.

Diet and Supplement Assessment

We interviewed women about the known and putative risk factors for epithelial ovarian cancer. Usual intake of antioxidants from diet and supplements was measured using a self-administered food frequency questionnaire (FFQ) developed by Gladys Block, modified to include specific questions on supplements and some other foods.

Additional questions were included to assess use of multivitamins and individual vitamins and minerals. To assess supplement use, the respondents were first asked whether they took any vitamins or minerals in the year before the reference date (date of diagnosis for cases and date of interview for controls) regularly, not on a regular basis, or not at all.

Those who used vitamins or minerals were asked whether they took a multi-vitamin supplement and, if so, the type (one-a-day, stress-tab, or therapeutic Theragram type), the number of tablets (1-2, 3-5, or > 5), and whether they were taken daily, weekly, or monthly.

For individual supplements including vitamins A, C, and E, beta-carotene, and selenium, we asked the number of tablets taken (1-2, 3-5, or > 5), dose, and whether they were taken daily, weekly, or monthly. For each individual supplement, respondents chose from a list of three or four common doses. We calculated the daily intake of these antioxidants from individual supplements and multivitamins.

Nutrient intakes from individual vitamin or mineral supplements (vitamins A, C, and E, beta-carotene, and selenium) were computed by multiplying the number of tablets taken by dose in milligrams or international units by frequency of use. For vitamin E, doses specified in international units were converted to milligrams, where 1 IU = 0.67 mg.

Consistent with previous literature, we reported vitamin A, beta-carotene, and lycopene in international units. To the total intake from individual supplements, we added the daily intake of each vitamin or mineral from the specified type of multivitamin used. For example, total daily vitamin C was computed by multiplying frequency by dose (mg/day) for a vitamin C supplement and adding this to the estimated vitamin C content from the multivitamins (mg/day).

For each antioxidant supplement, the reference group was nonusers, and two levels of consumption were analyzed using median cut points in the control population. For each food item, participants chose one of nine categories ranging from "never or < 1/mo" to " >/= 2/day" to indicate the frequency of their usual consumption and indicated the portion size. Average daily intake in milligrams for each vitamin and mineral from foods was computed using HHHQDietSys software (version 4.0, National Cancer Institute Applied Research Program, Bethesda, MD).

The algorithm used by this software for food items is as follows: [portion size (g) [lozenge] nutrient content (100 g) [lozenge] reported food frequency]/100. The level of consumption of each antioxidant was divided into thirds using cut points based on the distribution in the control population. Three variables for each individual antioxidant were then available for analysis: anti-oxidant intake from supplements, antioxidant intake from diet, and antioxidant intake from diet and supplements combined.

The HHHQ-DietSys software did not include a value for selenium from foods, and lycopene was not available from supplements. Vitamins A, C, and E and beta-carotene levels were available from supplements and diet. We report odds ratios (ORs) for antioxidants from supplements, diet, and supplements and diet combined. Statistical AnalysisWomen were excluded from the analysis if, on the dietary supplement questions, dose and/or frequency was left blank (n = 5), the FFQ was incomplete (i.e., >/= 30 food items were left blank, n = 41), or their energy intakes were implausibly low or high ( < 500 or > 5,000 kcal/day, n = 3).

After these exclusions, of the 419 enrolled participants, 375 women were included in the analysis. All five women who were missing information about supplements also had incomplete FFQs. Because the hospital-based convenience controls differed from the community controls with respect to antioxidant use and other factors, the data were analyzed including and excluding this control group. We used unconditional logistic regression in SAS (SAS Institute, Cary, NC) to estimate relative risks, adjusting for confounders, using ORs and 95% confidence intervals (CIs).

The following potential confounders did not have an effect on the associations studied: education, income, age at menarche and menopause, smoking (ever/never), talc use, and breast-feeding history (ever/never). Age (10-yr intervals), parity (nulliparous, 1-2 live births, and > 2 live births), use of oral contraceptives (ever/never), family history of breast and/or ovarian cancer in a first-degree relative (no/yes), total daily caloric intake ( < 2,000 and > 2,000 kcal/day), and an overweight body mass index ( > 25.0 kg/m 2 ) proved to be confounders. These factors were controlled for in the multi-variate analyses.

We compared the means (t-test) of antioxidant intake from diet among users and nonusers of supplements to examine whether supplement users consume higher quantities of antioxidants from foods than nonusers.

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