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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

A Prospective Study on Dietary Acrylamide Intake and the Risk for Breast, Endometrial, and Ovarian Cancers

Kathryn M. Wilson, Lorelei A. Mucci, Bernard A. Rosner and Walter C. Willett
Kathryn M. Wilson
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Lorelei A. Mucci
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Bernard A. Rosner
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Walter C. Willett
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DOI: 10.1158/1055-9965.EPI-10-0391 Published October 2010
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    Figure 1.

    Food contributors to acrylamide intake, 1998.

Tables

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  • Table 1.

    Age standardized characteristics of the study population in 1990

    Quintile of calorie-adjusted acrylamide intake
    Q1 (low)Q2Q3Q4Q5 (high)
    Age in 19905858575655
    Acrylamide intake (μg/d)913161926
    Acrylamide by body weight (μg/kg/d)0.130.200.240.300.42
    BMI2626262626
    Height (in)6465656564
    Current smokers (%)13%13%15%19%26%
    Physical activity (met-h/wk)1716161513
    Diabetes (%)3.6%3.0%2.8%2.8%2.4%
    Hypertension (%)19%19%18%16%16%
    Age at menarche < 13 (%)50%48%50%49%48%
    Nulliparous (%)7%7%6%6%6%
    Ever lactated (%)55%58%58%56%51%
    Premenopausal (%)21%23%23%23%23%
    Age at menopause (among postmenopausal)4747474747
    Current PMH use (% among postmenopausal)32%34%35%34%30%
    Tubal ligation (%)16%17%17%18%18%
    Hysterectomy (simple) (%)31%31%31%31%32%
    Double oophorectomy (%)16%16%15%16%16%
    Family history of breast cancer (%)9%10%10%11%10%
    Family history ovarian cancer (%, 1992)2.3%2.8%2.5%2.7%2.6%
    History of benign breast disease (%)39%41%41%41%39%
    Nutrient Intakes (per day)*
        Energy intake (kcal)1,7111,7761,7771,7531,674
        Alcohol (g)5.75.65.45.14.6
        Total fat (g)5656575860
        Animal fat (g)3432323233
        Trans fat (g)2.42.62.72.93.3
        Carbohydrates (g)195197197196192
        Glycemic index5252535353
        Folate (μg)447431422410389
        Caffeine (mg)155214261321421
    Intakes of high acrylamide foods (servings per day)
        Coffee1.01.82.22.83.4
        Breakfast cereal0.30.30.40.40.4
        French fries0.010.030.040.060.11
        Potato chips0.040.10.10.10.2
        Potatoes (baked, roasted, mashed)0.30.30.30.30.3
        Baked goods†0.50.70.80.80.8

    NOTE: Data (except for age) were directly standardized to the age distribution of the entire cohort. Means or percentages are shown as indicated. Characteristics of the population for breast cancer analysis is shown. Women were censored at the time of double oophorectomy for the ovarian cancer analysis, and women were censored at the time of hysterectomy for the endometrial cancer analysis.

    • ↵*All nutrients except alcohol are adjusted for total energy intake using the residual method.

    • ↵†Cookies, brownies, donuts, cake, sweet rolls, pie.

  • Table 2.

    Relative risk (and 95% confidence interval) of breast, endometrial, and ovarian cancers by quintile of calorie-adjusted acrylamide intake, 1980 to 2006

    Quintile of calorie-adjusted acrylamide intakeP for trend
    Q1 (low)Q2Q3Q4Q5 (high)
    Median intake (μg/d)8.712.715.719.025.1
    Breast cancer
            No. of cases1,2821,2801,3311,2871,121
            Person-years405,391404,518404,349404,769405,644
            Age-adjusted RR*1.000.94 (0.87-1.02)0.99 (0.92-1.07)0.99 (0.91-1.07)0.94 (0.87-1.02)0.36
            MV RR†1.000.93 (0.86-1.01)0.98 (0.91-1.06)0.98 (0.90-1.06)0.95 (0.87-1.03)0.50
        Never smokers only
            No. of cases652610582516392
            Person-years210,666198,085187,783171,665151,532
            Age-adjusted RR*1.000.94 (0.84-1.05)0.96 (0.86-1.08)0.96 (0.85-1.08)0.90 (0.80-1.03)0.21
            MV RR†1.000.91 (0.81-1.02)0.93 (0.83-1.05)0.94 (0.84-1.06)0.89 (0.78-1.02)0.18
    Endometrial cancer
            No. of cases8810010610288
            Person-years277,776277,073276,839277,409277,789
            Age-adjusted RR*1.001.07 (0.80-1.43)1.17 (0.88-1.56)1.15 (0.86-1.54)1.12 (0.83-1.52)0.41
            MV RR‡1.001.12 (0.83-1.50)1.31 (0.97-1.77)1.35 (0.99-1.84)1.41 (1.01-1.97)0.03
        Never smokers only
            No. of cases5347595642
            Person-years144,400135,320128,534116,601102,813
            Age-adjusted RR*1.000.93 (0.63-1.39)1.30 (0.89-1.90)1.37 (0.93-2.01)1.31 (0.86-2.00)0.06
            MV RR‡1.000.97 (0.64-1.46)1.35 (0.90-2.02)1.47 (0.97-2.24)1.43 (0.90-2.28)0.04
    Ovarian cancer
            No. of cases8775958178
            Person-years246,187245,523245,327245,667246,155
            Age-adjusted RR*1.000.85 (0.62-1.16)1.10 (0.81-1.47)0.95 (0.70-1.29)1.00 (0.73-1.37)0.78
            MV RR§1.000.93 (0.68-1.29)1.29 (0.94-1.76)1.17 (0.84-1.64)1.25 (0.88-1.77)0.12
        Never smokers only
            No. of cases4038312423
            Person-years126,888118,416112,475101,84991,082
            Age-adjusted RR*1.001.03 (0.65-1.63)0.92 (0.57-1.48)0.82 (0.49-1.37)0.92 (0.54-1.55)0.53
            MV RR§1.001.17 (0.72-1.88)1.04 (0.63-1.74)1.11 (0.63-1.94)1.19 (0.66-2.15)0.63

    Abbreviations: RR, relative risk; MV, multivariable.

    • ↵*Age-adjusted models are adjusted for age in months and calendar year.

    • ↵†Breast cancer multivariable models additionally adjusted for smoking (never, past <25 cigarettes per day, past ≥25 cigarettes per day, current <25 cigarettes per day, current ≥25 cigarettes per day), BMI (<18.5, 18.5 to <20, 20 to <22.5, 22.5 to <25, 25 to <30, ≥30 kg/m2), height (quartiles), menopausal status/age at menopause/PMH use (premenopausal; uncertain status; postmenopausal and age at menopause <45, 45-52, or >52 y; and PMH use never, former, current <5 y, or current ≥5 y), parity and age at first birth (nulliparous, parity 1-2 and age at first birth <25 y, parity 1-2 and age at first birth 25 to <30 y, parity 1-2 and age at first birth ≥30 y, parity 3-4 and age at first birth <25 y, parity 3-4 and age at first birth 25 to <30 y, parity 3-4 and age at first birth ≥30 y, parity ≥5 and age at first birth <25 y, parity ≥5 and age at first birth ≥25 y), family history of breast cancer (yes/no), benign breast disease (yes/no), age at menarche (<13, 13, ≥14 y), physical activity (≤18 or >18 MET-h/wk), folate, glycemic index, and animal fat intake (quintiles), alcohol (continuous; grams per day), and energy intake (continuous; kilocalories per day).

    • ↵‡Endometrial cancer multivariable models additionally adjusted for smoking (see categories for breast cancer), BMI (<20, 20 to <21, 21 to <22, 22 to <23, 23 to <24, 24 to <25, 25 to <27, 27 to <29, 29 to <30, 30 to <32, 32 to <35, 35 to <40, ≥40 kg/m2), age at menarche (<13, 13, ≥14 y), menopausal status/age at menopause/PMH use (see categories for breast cancer), parity (nulliparous, 1-2, 3-4, ≥5), oral contraceptive use (never, 0-3, >3 to <5, ≥5 y of use), high blood pressure (yes/no), diabetes (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day).

    • ↵§Ovarian cancer multivariable models additionally adjusted for smoking (see categories for breast cancer), BMI (see categories for breast cancer), parity (see categories for endometrial cancer), oral contraceptive use (see categories for endometrial cancer), menopausal status and PMH use (premenopausal, uncertain status, postmenopausal and never used PMH, postmenopausal and former PMH, postmenopausal and current PMH use), tubal ligation (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day).

  • Table 3.

    Relative risk (and 95% confidence interval) of breast, endometrial, and ovarian cancers by quintile of calorie-adjusted acrylamide intake according to menopausal status and BMI, 1980 to 2006

    Quintile of calorie-adjusted acrylamide intakeP for trendP for interaction
    Q1 (low)Q2Q3Q4Q5 (high)
    By menopausal status
        Breast cancer
            Postmenopausal (n)1,0511,0791,1151,012822
            MV RR*1.000.92 (0.84-1.00)0.97 (0.89-1.06)0.93 (0.85-1.01)0.93 (0.84-1.02)0.22
            Premenopausal (n)1651411482012270.27
            MV RR*1.000.96 (0.76-1.21)0.96 (0.76-1.21)1.17 (0.94-1.46)1.07 (0.87-1.33)0.23
        Endometrial cancer
            Postmenopausal (n)7487968865
            MV RR†1.001.11 (0.80-1.53)1.36 (0.98-1.88)1.38 (0.98-1.94)1.29 (0.89-1.89)0.11
            Premenopausal (n)1212911210.15
            MV RR†1.001.09 (0.46-2.62)1.00 (0.39-2.58)0.85 (0.32-2.26)2.27 (0.96-5.40)0.05
        Ovarian cancer
            Postmenopausal (n)6856716152
            MV RR‡1.000.90 (0.62-1.30)1.30 (0.91-1.87)1.19 (0.81-1.76)1.16 (0.76-1.78)0.28
            Premenopausal (n)14161619250.30
            MV RR‡1.001.10 (0.51-2.41)1.48 (0.69-3.17)1.32 (0.61-2.86)1.63 (0.76-3.46)0.19
    By BMI
        Breast cancer
            BMI < 25 kg/m2 (n)636629614593541
            MV RR*1.000.96 (0.85-1.07)0.96 (0.85-1.07)0.95 (0.84-1.06)0.92 (0.81-1.03)0.17
            BMI ≥ 25 kg/m2 (n)6466517176945800.60
            MV RR*1.000.92 (0.82-1.02)1.01 (0.90-1.13)1.01 (0.90-1.13)0.97 (0.86-1.09)0.87
        Endometrial cancer
            BMI < 25 kg/m2 (n)2032384031
            MV RR†1.001.70 (0.94-3.09)2.08 (1.15-3.77)2.41 (1.32-4.38)2.51 (1.32-4.77)0.004
            BMI ≥ 25 kg/m2 (n)68676862570.20
            MV RR†1.000.92 (0.64-1.32)1.07 (0.74-1.54)0.99 (0.67-1.46)1.08 (0.72-1.64)0.62
        Ovarian cancer
            BMI < 25 kg/m2 (n)4447483852
            MV RR‡1.001.27 (0.82-1.97)1.56 (1.00-2.43)1.47 (0.92-2.36)1.84 (1.14-2.97)0.01
            BMI ≥ 25 kg/m2 (n)44294243290.45
            MV RR‡1.000.66 (0.40-1.08)1.01 (0.64-1.61)0.95 (0.58-1.54)0.84 (0.49-1.44)0.86
    • ↵*Breast cancer multivariable models adjusted for age in months, calendar year, smoking (never, past <25 cigarettes per day, past ≥25 cigarettes per day, current <25 cigarettes per day, current ≥25 cigarettes per day), BMI (<18.5, 18.5 to <20, 20 to <22.5, 22.5 to <25, 25 to <30, ≥30 kg/m2), height (quartiles), parity and age at first birth (nulliparous, parity 1-2 and age at first birth <25 y, parity 1-2 and age at first birth 25 to <30 y, parity 1-2 and age at first birth ≥30 y, parity 3-4 and age at first birth <25 y, parity 3-4 and age at first birth 25 to <30 y, parity 3-4 and age at first birth ≥30 y, parity ≥5 and age at first birth <25 y, parity ≥5 and age at first birth ≥25 y), family history of breast cancer (yes/no), benign breast disease (yes/no), age at menarche (<13, 13, ≥14 y), physical activity (≤18 or >18 MET-h/wk), folate, glycemic index, and animal fat intake (quintiles), alcohol (continuous; grams per day), and energy intake (continuous; kilocalories per day). Postmenopausal model adjusted for joint age at menopause and PMH use variable (age at menopause <45, 45-52, or >52 y, and PMH use never, former, current <5 y, or current ≥5 y). BMI models adjusted for joint menopausal status, age at menopause, and PMH use variable (premenopausal; uncertain status; postmenopausal and age at menopause <45, 45-52, or >52 y; and PMH use never, former, current <5 y, or current ≥5 y).

    • ↵†Endometrial cancer multivariable models adjusted for age in months, calendar year, smoking (see categories for breast cancer), BMI (<20, 20 to <21, 21 to <22, 22 to <23, 23 to <24, 24 to <25, 25 to <27, 27 to <29, 29 to <30, 30 to <32, 32 to <35, 35 to <40, ≥40 kg/m2), age at menarche (<13, 13, ≥14 y), parity (nulliparous, 1-2, 3-4, ≥5), oral contraceptive use (never, 0-3, >3 to <5, ≥5 y of use), high blood pressure (yes/no), diabetes (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day). Postmenopausal model adjusted for joint age at menopause and PMH use variable (see categories for breast cancer). BMI models adjusted for joint menopausal status, age at menopause, and PMH use variable (see categories for breast cancer).

    • ↵‡Ovarian cancer multivariable models adjusted for age in months, calendar year, smoking (see categories for breast cancer), BMI (see categories for breast cancer), parity (see categories for endometrial cancer), oral contraceptive use (see categories for endometrial cancer), tubal ligation (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day). Postmenopausal model adjusted for PMH use (never, former, or current). BMI models adjusted for joint menopausal status and PMH use variable (premenopausal, uncertain status, postmenopausal and never PMH use, postmenopausal and former PMH use, and postmenopausal and current PMH use).

  • Table 4.

    Relative risk (and 95% confidence interval) of breast cancer and ovarian cancer subtypes by quintile of calorie-adjusted acrylamide intake

    Quintile of calorie-adjusted acrylamide intakeP for trend
    Q1 (low)Q2Q3Q4Q5 (high)
    Breast cancer
        ER+/PR+ (n)520594606580505
        MV RR*1.000.98 (0.87-1.10)0.99 (0.88-1.12)0.99 (0.87-1.11)0.99 (0.87-1.13)0.99
        ER+/PR− (n)136161173148119
        MV RR*1.001.09 (0.87-1.38)1.20 (0.95-1.51)1.08 (0.85-1.37)1.04 (0.80-1.34)0.88
        ER−/PR+ (n)2823203532
        MV RR*1.000.78 (0.45-1.37)0.66 (0.37-1.20)1.18 (0.70-1.98)1.09 (0.63-1.87)0.35
        ER−/PR− (n)178159175174153
        MV RR*1.000.86 (0.69-1.07)0.94 (0.76-1.17)0.95 (0.77-1.19)0.88 (0.70-1.11)0.52
    Ovarian cancer
        Invasive (n)7266887166
        MV RR†1.000.98 (0.69-1.38)1.45 (1.03-2.03)1.28 (0.89-1.83)1.31 (0.89-1.92)0.09
        Borderline (n)1497912
        MV RR†1.000.74 (0.31-1.77)0.57 (0.22-1.51)0.74 (0.29-1.87)0.99 (0.40-2.46)0.92
        Serous (n)4046545253
        MV RR†1.001.11 (0.71-1.73)1.43 (0.92-2.22)1.39 (0.88-2.20)1.58 (0.99-2.52)0.04
        Serous Invasive (n)3339484443
        MV RR†1.001.14 (0.70-1.86)1.59 (0.99-2.57)1.52 (0.92-2.51)1.67 (0.99-2.81)0.04

    Abbreviation: cum. avg., cumulative average.

    • ↵*Breast cancer models adjusted for age in months, calendar year, smoking (never, past <25 cigarettes per day, past ≥25 cigarettes per day, current <25 cigarettes per day, current ≥25 cigarettes per day), BMI (<18.5, 18.5 to <20, 20 to <22.5, 22.5 to <25, 25 to <30, ≥30 kg/m2), height (quartiles), parity and age at first birth (nulliparous, parity 1-2 and age at first birth <25 y, parity 1-2 and age at first birth 25 to <30 y, parity 1-2 and age at first birth ≥30 y, parity 3-4 and age at first birth <25 y, parity 3-4 and age at first birth 25 to <30 y, parity 3-4 and age at first birth ≥30 y, parity ≥5 and age at first birth <25 y, parity ≥5 and age at first birth ≥25 y), family history of breast cancer (yes/no), benign breast disease (yes/no), age at menarche (<13, 13, ≥14 y), physical activity (≤18 or >18 MET-h/wk), folate, glycemic index, and animal fat intake (quintiles), alcohol (continuous; grams per day), and energy intake (continuous; kilocalories per day). Postmenopausal model adjusted for joint age at menopause and PMH use variable (age at menopause <45, 45-52, or >52 y AND PMH use never, former, current <5 y, or current ≥5 y).

    • ↵†Ovarian cancer models adjusted for age in months, calendar year, smoking (see categories for breast cancer), BMI (see categories for breast cancer), parity (nulliparous, 1-2, 3-4, ≥5), oral contraceptive use (never, 0-3, >3 to <5, ≥5 y of use), menopausal status and PMH use (premenopausal, uncertain status, postmenopausal and never used PMH, postmenopausal and former PMH, postmenopausal and current PMH use), tubal ligation (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day).

  • Table 5.

    Relative risk (and 95% confidence interval) of endometrial and ovarian cancers by quintile of calorie-adjusted acrylamide intake additionally adjusting for high-acrylamide foods, 1980 to 2006

    Quintile of calorie-adjusted acrylamide intakeP for trend
    Q1 (low)Q2Q3Q4Q5 (high)
    Endometrial cancer
        No. of cases8810010610288
        Person-years277,776277,073276,839277,409277,789
        MV RR*1.001.12 (0.83-1.50)1.31 (0.97-1.77)1.35 (0.99-1.84)1.41 (1.01-1.97)0.03
        MV RR + coffee†1.001.08 (0.80-1.46)1.26 (0.93-1.72)1.31 (0.95.80)1.37 (0.97-1.94)0.05
        MV RR + cereal†1.001.09 (0.81-1.47)1.27 (0.94-1.72)1.31 (0.95-1.79)1.37 (0.98-1.93)0.05
        MV RR + French fries†1.001.16 (0.85-1.58)1.41 (1.02-1.95)1.51 (1.06-2.16)1.69 (1.11-2.57)0.01
        MV RR + potato chips†1.001.11 (0.82-1.49)1.29 (0.94-1.75)1.32 (0.95-1.83)1.37 (0.95-1.97)0.06
    Ovarian cancer
        No. of cases8775958178
        Person-years246,187245,523245,327245,667246,155
        MV RR‡1.000.93 (0.68-1.29)1.29 (0.94-1.76)1.17 (0.84-1.64)1.25 (0.88-1.77)0.12
        MV RR + coffee†1.000.93 (0.67-1.29)1.29 (0.94-1.78)1.18 (0.83-1.65)1.24 (0.87-1.78)0.15
        MV RR + cereal†1.000.92 (0.67-1.27)1.26 (0.92-1.73)1.15 (0.82-1.62)1.23 (0.86-1.76)0.15
        MV RR + French fries†1.000.90 (0.64-1.25)1.24 (0.88-1.74)1.15 (0.78-1.68)1.29 (0.83-1.99)0.14
        MV RR + potato chips†1.000.90 (0.65-1.24)1.18 (0.85-1.63)1.02 (0.72-1.46)1.01 (0.69-1.49)0.82
    • ↵*Endometrial cancer multivariable models adjusted for age in months, calendar year, smoking (never, past <25 cigarettes per day, past ≥25 cigarettes per day, current <25 cigarettes per day, current ≥25 cigarettes per day), BMI (<20, 20 to <21, 21 to <22, 22 to <23, 23 to <24, 24 to <25, 25 to <27, 27 to <29, 29 to <30, 30 to <32, 32 to <35, 35 to <40, ≥40 kg/m2), age at menarche (<13, 13, ≥14 y), menopausal status/age at menopause/PMH use (premenopausal; uncertain status; postmenopausal and age at menopause <45, 45-52, or >52 y; and PMH use never, former, current <5 y, or current ≥5 y), parity (nulliparous, 1-2, 3-4, ≥5), oral contraceptive use (never, 0-3, >3 to <5, ≥5 y of use), high blood pressure (yes/no), diabetes (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day).

    • ↵†Adjusted as in multivariable model and additionally adjusted for intake of given food in quintiles (for acrylamide quintile analysis) or as a continuous variable using the median intake for each quintile (for acrylamide P for trend analysis).

    • ↵‡Ovarian cancer multivariable models adjusted for age in months, calendar year, smoking (see categories for endometrial cancer), BMI (<18.5, 18.5 to <20, 20 to <22.5, 22.5 to <25, 25 to <30, ≥30 kg/m2), parity (see categories for endometrial cancer), oral contraceptive use (see categories for endometrial cancer), menopausal status and PMH use (premenopausal, uncertain status, postmenopausal and never used PMH, postmenopausal and former PMH, postmenopausal and current PMH use), tubal ligation (yes/no), physical activity (≤18 or >18 MET-h/wk), caffeine intake (quintiles), and energy intake (continuous; kilocalories per day).

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Cancer Epidemiology Biomarkers & Prevention: 19 (10)
October 2010
Volume 19, Issue 10
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A Prospective Study on Dietary Acrylamide Intake and the Risk for Breast, Endometrial, and Ovarian Cancers
Kathryn M. Wilson, Lorelei A. Mucci, Bernard A. Rosner and Walter C. Willett
Cancer Epidemiol Biomarkers Prev October 1 2010 (19) (10) 2503-2515; DOI: 10.1158/1055-9965.EPI-10-0391

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A Prospective Study on Dietary Acrylamide Intake and the Risk for Breast, Endometrial, and Ovarian Cancers
Kathryn M. Wilson, Lorelei A. Mucci, Bernard A. Rosner and Walter C. Willett
Cancer Epidemiol Biomarkers Prev October 1 2010 (19) (10) 2503-2515; DOI: 10.1158/1055-9965.EPI-10-0391
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