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. 2013 Feb 5;105(3):219–236. doi: 10.1093/jnci/djs635

Table 5.

Pooled multivariable relative risks (95% confidence interval) of breast cancer by estrogen receptor status for a 300g/day increment in fruit and vegetable intake by other risk factors*

Effect modifiers No. of case patients Total fruits and vegetables RR (95% CI) P interaction† Total vegetables RR (95% CI) P interaction† Total fruits RR (95% CI) P interaction†
Subgroup results
    Menopausal status
        ER−
         Premenopausal‡,§ 956 1.00 (0.91 to 1.10) .41 0.85 (0.66 to 1.04) .35 1.07 (0.96 to 1.21) 0.09
         Postmenopausal|| 2809 0.96 (0.92 to 1.00) 0.91 (0.83 to 1.00) 0.97 (0.92 to 1.03)
        ER+
         Premenopausal‡,§ 2276 0.98 (0.92 to 1.05) .44 0.93 (0.83 to 1.05) .08 1.01 (0.92 to 1.11) .85
         Postmenopausal 13 450 1.01 (0.98 to 1.03) 1.06 (1.02 to 1.10) 1.00 (0.96 to 1.03)
    Postmenopausal hormone use¶
        ER−
         Never# 1696 0.94 (0.88 to 1.00) .18 0.88 (0.77 to 1.00) .35 0.93 (0.84 to 1.03) .30
         Ever** 1374 1.00 (0.94 to 1.06) 0.97 (0.85 to 1.10) 1.02 (0.95 to 1.10)
        ER+
         Never# 6128 1.01 (0.98 to 1.04) .55 1.08 (1.01 to 1.16) .14 0.98 (0.94 to 1.03) .92
         Ever†† 7160 1.00 (0.97 to 1.03) 1.03 (0.98 to 1.09) 1.00 (0.95 to 1.05)
    Oral contraceptive use ‡‡
        ER−
         Never 2029 0.93 (0.87 to 0.99) .67 0.86 (0.74 to 0.99) .49 0.94 (0.87 to 1.03) .88
         Ever 2337 0.95 (0.90 to 1.00) 0.91 (0.81 to 1.01) 0.96 (0.90 to 1.03)
        ER+
         Never 9658 0.99 (0.98 to 1.00) .04 1.00 (0.9801.02) .15 0.99 (0.97 to 1.01) .08
         Ever 8860 1.01 (1.00 to 1.01) 1.02 (1.00 to 1.04) 1.00 (0.99 to 1.02)
    Multivitamin use§§
        ER−
         No|||| 2131 0.97 (0.90 to 1.04) .75 0.91 (0.79 to 1.04) .50 0.98 (0.90 to 1.07) .87
         Yes¶¶ 1702 0.94 (0.89 to 0.99) 0.84 (0.75 to 0.95) 0.96 (0.90 to 1.03)
        ER+
         No 8708 1.01 (1.00 to 1.01) .22 1.01 (0.99 to 1.03) .57 1.01 (1.00 to 1.02) .15
         Yes 7594 1.00 (0.99 to 1.01) 1.01 (0.99 to 1.03) 0.99 (0.98 to 1.01)
    Alcohol consumption ##
        ER−
         Never 1518 0.92 (0.87 to 0.98) .49 0.88 (0.75 to 1.02) .18 0.94 (0.86 to 1.02) .81
         <1 drink/day*** 2422 0.96 (0.91 to 1.01) 0.93 (0.84 to 1.04) 0.97 (0.91 to 1.03)
         ≥1drink/day††† 475 0.91 (0.80 to 1.02) 0.72 (0.56 to 0.93) 0.95 (0.83 to 1.10)
        ER+
         Never 6569 1.00 (0.99 to 1.01) .94 1.01 (0.99 to 1.03) .74 1.00 (0.98 to 1.02) .96
         <1 drink/day‡‡‡ 10 256 1.00 (0.99 to 1.01) 1.00 (0.98 to 1.02) 1.00 (0.98 to 1.01)
         ≥1drink/day§§§ 2474 0.99 (0.97 to 1.01) 1.02 (0.99 to 1.05) 0.99 (0.97 to 1.01)
Smoking status||||||
        ER−
         Never 2303 0.94 (0.90 to 0.99) .71 0.89 (0.80 to 0.99) .55 0.95 (0.90 to 1.02) .86
         Past¶¶¶ 1277 0.97 (0.90 to 1.04) 0.94 (0.80 to 1.09) 0.98 (0.90 to 1.06)
         Current### 701 0.93 (0.84 to 1.02) 0.82 (0.66 to 1.02) 0.96 (0.83 to 1.12)
        ER+
         Never 9228 1.00 (0.99 to 1.01) .89 1.01 (1.00 to 1.03) .18 1.00 (0.98 to 1.01) .68
         Past**** 6069 1.00 (0.99 to 1.02) 1.02 (1.00 to 1.04) 1.00 (0.98 to 1.02)
         Current**** 2107 1.00 (0.98 to 1.01) 0.98 (0.95 to 1.01) 1.00 (0.98 to 1.03)
Body mass index
        ER−
         <25kg/m2 2572 0.94 (0.89 to 0.98) .58 0.88 (0.79 to 0.99) .97 0.95 (0.89 to 1.01) .59
         ≥25kg/m2 2163 0.96 (0.89 to 1.04) 0.89 (0.77 to 1.02) 0.97 (0.89 to 1.06)
        ER+
         <25kg/m2 10 380 1.00 (0.99 to 1.00) .24 1.01 (0.99 to 1.02) .40 0.99 (0.98 to 1.00) .32
         ≥25kg/m2 9289 1.00 (0.99 to 1.01) 1.01 (0.99 to 1.03) 1.00 (0.99 to 1.02)
Age at diagnosis
        ER−
         <64 y 2981 0.93 (0.88 to 0.98) .22 0.87 (0.78 to 0.97) .52 0.94 (0.89 to 1.00) .23
         ≥64 y†††† 1803 0.97 (0.92 to 1.03) 0.91 (0.78 to 1.06) 0.99 (0.93 to 1.06)
        ER+
         <64 y 9323 1.00 (0.99 to 1.01) .86 1.00 (0.99 to 1.02) .22 1.00 (0.99 to 1.01) .30
         ≥64 y‡‡‡‡ 10 080 1.00 (0.99 to 1.01) 1.02 (0.99 to 1.04) 1.00 (0.98 to 1.01)
    Family history of breast cancer§§§§
        ER−
         No 3783 0.96 (0.93 to 1.00) .23 0.92 (0.83 to 1.02) .14 0.98 (0.93 to 1.03) .92
         Yes|||||||| 583 0.90 (0.81 to 1.00) 0.75 (0.56 to 1.01) 0.97 (0.85 to 1.11)
        ER+
         No 15 759 1.00 (0.99 to 1.01) .45 1.01 (0.99 to 1.02) .99 1.00 (0.99 to 1.01) .38
         Yes¶¶¶¶ 2732 1.00 (0.97 to 1.02) 1.01 (0.97 to 1.04) 0.99 (0.96 to 1.02)
Race ####
        ER−
         White***** 3875 0.94 (0.91 to 0.98) .71 0.87 (0.80 to 0.95) .20 0.96 (0.91 to 1.01) .99
         Black††††† 359 0.95 (0.84 to 1.07) 0.81 (0.58 to 1.14) 0.97 (0.84 to 1.11)
         Other‡‡‡‡‡ 276 1.01 (0.84 to 1.21) 1.11 (0.73 to 1.69) 0.97 (0.81 to 1.16)
        ER+
         White***** 17 439 1.01 (0.99 to 1.03) .47 1.03 (0.98 to 1.07) .73 1.01 (0.97 to 1.04) .59
         Black§§§§§ 666 1.03 (0.88 to 1.20) 1.09 (0.88 to 1.35) 0.99 (0.83 to 1.18)
         Other|||||||||| 961 0.96 (0.89 to 1.04) 0.99 (0.86 to 1.15) 0.95 (0.86 to 1.05)

* The relative risks were adjusted for ethnicity (White, African-American, Hispanic, Asian, others), family history of breast cancer (yes, no), personal history of benign breast disease (yes, no), alcohol consumption (nondrinkers, >0 to <5, 5 to <15, 15 to <30, ≥30g/day), smoking status (never, past, current), education (<high school, high school, >high school), physical activity (low, medium, high), age at menarche (<11, 11 to 12, 13 to 14, ≥15 years), body mass index (<23, 23 to <25, 25 to <30, ≥30kg/m2), height (<1.60, 1.60 to <1.65, 1.65 to <1.70, 1.70 to <1.75, ≥1.75 m), oral contraceptive use (never, ever), menopausal status (premenopausal women, never user of hormone replacement therapy among postmenopausal women, past user of hormone replacement therapy among postmenopausal women, and current user of hormone replacement therapy among postmenopausal women), energy intake (kcal/day, continuous), combination between parity (0, 1 to 2, ≥3) and age of first birth (≤25, >25 years). Age in years and year of questionnaire return were included as stratification variables. The effect modifiers was not included as a covariate in the models evaluating that effect modifier. All statistical tests were two-sided. RR = relative risk; CI = confidence interval; ER = estrogen receptor.

† P, test for interaction was calculated by using a mixed-effects meta-regression.

‡ The Beta-Carotene and Retinol Efficacy Trial, Iowa Women’s Health Study, Netherlands Cohort Study, and Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial were not included in this analyses because all case patients were postmenopausal women.

§ The National Institutes of Health–AARP Diet and Health Study, Breast Cancer Detection Demonstration Project Follow-up Study, CLUE II: Campaign Against Cancer and Heart Disease and Cancer Prevention Study II Nutrition Cohort were not included in this stratum because few case patients (n < 15) were premenopausal women.

|| The Nurses’ Health Study II and Women’s Lifestyle and Health Study were not included in this stratum because few case patients (n < 15) were postmenopausal women.

¶ The Beta-Carotene and Retinol Efficacy Trial, Japan Public Health Center-Based Prospective Study I, and New York University Women’s Health Study were not included in this analysis because this variable was not measured.

# The Nurses’ Health Study II was not included in this stratum because few case patients (n < 15) were never users of postmenopausal hormones.

** CLUE II: Campaign Against Cancer and Heart Disease, Nurses’ Health Study II, Prospective Study on Hormones, Diet and Breast Cancer, and Women’s Lifestyle and Health Study were not included in this stratum, because few case patients (n < 15) were ever users of postmenopausal hormones.

†† The Women’s Lifestyle and Health Study were not included in this stratum, because few case patients (n < 15) were ever users of postmenopausal hormones.

‡‡ The Beta-Carotene and Retinol Efficacy Trial, Japan Public Health Center-Based Prospective Study I, and New York University Women’s Health Study were not included in these analyses, because this variable was not measured.

§§ The Canadian National Breast Screening Study, Prospective Study on Hormones, Diet and Breast Cancer, Swedish Mammography Cohort, and Women’s Lifestyle and Health Study were not included in these analyses because data on multivitamin use were not available at baseline in these studies.

|||| The Beta-Carotene and Retinol Efficacy Trial and the CLUE II: Campaign Against Cancer and Heart Disease were not included in this stratum, because few case patients (n < 15) were nonusers of multivitamins.

¶¶ The Japan Public Health Center-Based Prospective Study I was not included in this stratum, because few case patients (n < 15) were using multivitamins.

## The Black Women’s Health Study and New York University Women’s Health Study were not included in these analyses because data on alcohol consumption were not available in our database or was not measured at baseline, respectively.

*** The Japan Public Health Center-Based Prospective Study I and the Beta-Carotene and Retinol Efficacy Trial were not included in this stratum, because few case patients (n < 15) drank alcohol.

††† The Beta-Carotene and Retinol Efficacy Trial, Japan Public Health Center-Based Prospective Study I, CLUE II: Campaign Against Cancer and Heart Disease, Swedish Mammography Cohort, and Women’s Lifestyle and Health Study were not included in this stratum, because few case patients (n < 15) drank at least one alcoholic beverage a day.

‡‡‡ The Japan Public Health Center-Based Prospective Study I was not included in this stratum, because few case patients (n < 15) drank alcohol.

§§§ The Japan Public Health Center-Base Prospective Study I and CLUE II: Campaign Against Cancer and Heart Disease were not included in this stratum because few case patients (n < 15) drank at least one alcoholic beverage a day.

|||||| The New York University Women’s Health Study and Swedish Mammography Cohort were not included in these analyses because smoking status was not measured at baseline.

¶¶¶ The Beta-Carotene and Retinol Efficacy Trial, CLUE II: Campaign Against Cancer and Heart Disease, Japan Public Health Center-Based Prospective Study I, and the Prospective Study on Hormones, Diet and Breast Cancer were not included in this stratum, because few case patients (n <15) were past smokers.

### CLUE II: Campaign Against Cancer and Heart Disease, Japan Public Health Center-Based Prospective Study I and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were not included in this stratum because few case patients (n < 15) were current smokers.

**** Japan Public Health Center-Based Prospective Study I was not included in this stratum because few case patients (n < 15) were past or current smokers.

†††† The Beta-Carotene and Retinol Efficacy Trial, Canadian National Breast Screening Study, Japan Public Health Center-Based Prospective Study I, Nurses’ Health Study (a), the Prospective Study on Hormones, Diet and Breast Cancer, and Women’s Lifestyle and Health Study were not included in this stratum, because few case patients (n < 15) were older than 64 years.

‡‡‡‡ The Nurses’ Health Study II, Women’s Lifestyle and Health Study, Japan Public Health Center-Based Prospective Study I, and The Canadian National Breast Screening Study were not included in this stratum, because few case patients (n < 15) were at least 64 years.

§§§§ The CLUE II: Campaign Against Cancer and Heart Disease and Melbourne Collaborative Cohort Study were not included in these analyses because this variable was not measured.

|||||||| The Beta-Carotene and Retinol Efficacy Trial, Japan Public Health Center-Based Prospective Study I, and the Prospective Study on Hormones, Diet and Breast Cancer were not included in this stratum because few case patients (n <15) had a family history of breast cancer.

¶¶¶¶ The Japan Public Health Center-Based Prospective Study I was not included in this stratum because few case patients (n < 15) had a family history of breast cancer.

#### The Canadian National Breast Screening Study was not included in these analyses because this variable was not measured.

***** The Black Women’s Health Study and The Japan Public Health Center-Based Prospective Study I were not included in this stratum because none of the participants were white.

††††† The Beta-Carotene and Retinol Efficacy Trial, The CLUE II: Campaign Against Cancer, The Japan Public Health Center-Based Prospective Study I, Melbourne Collaborative Cohort Study, Netherlands Cohort Study, Prospective Study on Hormones, Diet and Breast Cancer, Swedish Mammography Cohort, and Women’s Lifestyle and Health Study were not included in this stratum because few case patients (n < 15) were African-American.

‡‡‡‡‡ The Black Women’s Health Study, The Beta-Carotene and Retinol Efficacy Trial, The CLUE II: Campaign Against Cancer, Iowa Women’s Health Study, Melbourne Collaborative Cohort Study, Netherlands Cohort Study, Prospective Study on Hormones, Diet and Breast Cancer, Swedish Mammography Cohort, and Women’s Lifestyle and Health Study were not included in this stratum because few case patients (n < 15) were Hispanic, Asian, or other races.

§§§§§ The Breast Cancer Detection Demonstration Project Follow-up Study, The Beta-Carotene and Retinol Efficacy Trial, The CLUE II: Campaign Against Cancer, Cancer Prevention Study II Nutrition Cohort, California Teachers Study, Canadian National Breast Screening Study, Iowa Women’s Health Study, The Japan Public Health Center-Based Prospective Study I, Melbourne Collaborative Cohort Study, Nurses’ Health Study(a), Nurses’ Health Study II, Netherlands Cohort Study, Prospective Study on Hormones, Diet and Breast Cancer, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Swedish Mammography Cohort, Women’s Health Study, and Women’s Lifestyle and Health Study were not included in this stratum because few case patients (n < 15) were African-American.

|||||||||| The Breast Cancer Detection Demonstration Project Follow-up Study, the Black Women’s Health Study, The Beta-Carotene and Retinol Efficacy Trial, The CLUE II: Campaign Against Cancer, Cancer Prevention Study II Nutrition Cohort, Iowa Women’s Health Study, Melbourne Collaborative Cohort Study, Nurses’ Health Study II, Netherlands Cohort Study, New York University Women’s Health Study, Prospective Study on Hormones, Diet and Breast Cancer, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Swedish Mammography Cohort, Women’s Health Study, and Women’s Lifestyle and Health Study were not included in this stratum because few case patients (n < 15) were Hispanic, Asian, or other races.