cron-web.org

[A1CR]

It seems that "it has been suggested that dietary energy
intake restriction
may be related to reduced BRCA-associated breast cancer (BC)
risk" and the
paper below (1) reports that correcting for caloric intakes
and other
confounders resulted in no association with
http://en.wikipedia.org/wiki/Breast_cancer (BC), but did
with BC associated
with http://en.wikipedia.org/wiki/BRCA1 and
http://en.wikipedia.org/wiki/BRCA2 types of BC. -- This
paper (1) was, unfortunately, not a prospective study.
Unfortunately, also, the (2) paper from the same research
group was also not a prospective study, but a case-control
study. Much of the same apparently applies to (2), as
applied to (1), regarding the
role of CR.

Nkondjock A, Ghadirian P.
Diet quality and BRCA-associated breast cancer risk.
Breast Cancer Res Treat. 2006 Oct 25; [Epub ahead of print]
PMID: 17063275

Although it has been suggested that dietary energy intake
restriction may be
related to reduced BRCA-associated breast cancer (BC) risk
... Alternate
Healthy Eating Index (AHEI), the Diet Quality Index-Revised
(DQI-R), the
alternate Mediterranean Diet Index (aMED), the Canadian
Healthy Eating Index
(CHEI), and BRCA-associated BC risk, a case-control study
was carried out
within a cohort of 80 French-Canadian families with 250
members involving 89
carriers of BRCA genes affected by BC, 48 non-affected
carriers and 46
non-affected non-carriers. Odds ratios (ORs) and 95%
confidence intervals
(CIs) were calculated in unconditional logistic regression
models. After
adjustment for age, physical activity and total energy
intake, we did not
detect any association between the AHEI or aMED and BC.
However, a strong
and significant inverse relationship was apparent between
the DQI-R and CHEI
and BRCA-associated BC risk. ORs comparing the highest and
lowest tertiles
of diet quality scores were 0.35 (95%CI = 0.12-1.02; p ( )=
0.034 for trend)
for the DQI-R and 0.18 (95%CI = 0.05-0.68; p = 0.006 for
trend) for the
CHEI, respectively. These inverse associations were not the
result of a link
with any specific component of the diet quality indexes.
These results
suggest that dietary guidelines reflected by the DQI-R and
CHEI may
constitute preventive strategies for reducing
BRCA-associated BC risk.

2. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P.
Diet, lifestyle and BRCA-related breast cancer risk among
French-Canadians.
Breast Cancer Res Treat. 2006 Aug;98(3):285-294. Epub 2006
Mar 16.
PMID: 16541324

BACKGROUND: Although the connection between diet, lifestyle
and hormones
suggests that nutritional and lifestyle factors may exert an
influence in
the etiology of breast cancer (BC), it is not clear whether
these factors
operate in the same way in women with BRCA1 and BRCA2 (BRCA)
gene mutations
who already have an elevated BC risk. METHODS: A
case-control study was
conducted within a cohort of 80 French-Canadian families
with 250 members
involving 89 carriers of mutated BRCA gene affected with BC
and 48
non-affected carriers. A validated semi-quantitative food
frequency
questionnaire was used to ascertain dietary intake, and a
lifestyle core
questionnaire, to gather information on physical activity
and other
lifestyle risk factors. Odds ratios (ORs) and 95% confidence
intervals (CIs)
were calculated in unconditional logistic regression models.
RESULTS: After
adjustment for age, maximum lifetime body mass index (BMI)
and physical
activity, a positive association was found between total
energy intake and
BRCA-related BC risk. OR was 2.76 (95%CI: 1.10-7.02; p=0.026
for trend),
when comparing the highest tertile of intake with the
lowest. The intake of
other nutrients and dietary components was not significantly
associated with
the risk of BC. Age at the time the subjects reached maximum
BMI was
significantly related to an elevated BC risk (OR=2.90;
95%CI: 1.01-8.36;
p=0.046 for trend). In addition, a direct and significant
relationship was
noted between maximum weight gain since both age 18 and 30
years and BC
risk. The ORs were 4.64 (95%CI: 1.52-14.12; p=0.011 for
trend) for weight
gain since age 18 years and 4.11 (95%CI: 1.46-11.56; p=0.013
for trend) for
weight gain since age 30 years, respectively. No overall
association was
apparent between BRCA-related BC risk and BMI, smoking, and
physical
activity. CONCLUSION: The results of this preliminary study
suggest that
weight control in adulthood through dietary energy intake
restriction is an
important factor for the prevention of BRCA-related BC risk.

... Germline mutations in the BC susceptibility genes, BRCA1
and BRCA2
(BRCA) are known to cause susceptibility to BC and ovarian
cancer. Compared
with the general population, women who carry BRCA mutations
have a very high
lifetime risk of developing BC. Recent estimates show that
the lifetime risk
of developing BC associated with mutations in either BRCA1
or BRCA2
mutations is extremely high, around 87% by the time the
carriers reach age
70 years [2]. ...

Table 1. Selected characteristics of the study population
=======================================================
Variables Cases (n=89) (%) Controls (n=48) (%)
=======================================================
Age (years, mean±SD) 56.2±11.5 50.9±11.9*
20-29 1 0
30-39 3 13
40-49 27 42
50-59 30 27
60-69 24 10
70-79 13 4
80-89 2 4
Parity
Nulliparous 10 19
=/>1 92 81
Oral contraceptive use
Ever 78 85
Never 22 15
Hormone replacement therapy
Yes 17 26
No 83 74
Marital status
Single 7 6
Married/Common-law 78 75
Separated/Divorced 9 13
Widowed 9 6
Smoking
Ever 44 26
Never 44 22
Type of mutation
BRCA1 39 50
BRCA2 59 50
BRCA1 and BRCA2 2 0
Education attainment (years) 11.9±3.2 12.4±2.9
Age at menarche (years, mean±SD) 12.8±1.6 13.2±1.6
Age at menopause (years, mean±SD) 44.2±6.5 42.5±7.1
Smoking (packs-year, mean±SD) 13.9±21.0 14.7±19.7
Age at maximum weight (lbs, mean±SD) 46.2±13.3 38.8±13.3**
Weight at 18 (lbs, mean±SD) 116.6±14.6 118.8±14.4
Weight at 30 (lbs, mean ± SD) 129.9±21.9 127.4±15.7
Weight at 50 (lbs, mean ± SD) 141.6±27.5 137.3±22.7
Maximum lifetime weight (lbs, mean±SD) 156.4±30.6 145.2±21.9*
Weight gain since age 18 (lbs, mean±SD) 39.8±25.2 26.9±19.4**
Weight gain since age 30 (lbs, mean±SD) 26.6±21.0 18.3±15.3*
Physical activity (MET-hours/week, mean ± SD)
Moderate 23.1±16.6 18.9±12.5
Vigorous 7.7±13.2 10.7±15.4
Total 30.8±23.8 29.6±21.9
Fat intake (g, mean±SD) 97±49 78±38*
Total energy intake (kcal, mean±SD) 2589±1142 2167±830*
Fat (%) 33.5±7.2 32.2±7.2
Protein (%) 14.4±2.9 14.5±2.4
Carbohydrate (%) 52.4±8.5 53.0±9.9
Alcohol (%) 2.4±3.4 3.4±4.4
=======================================================
Significantly different from cases (the Student's t-test
for continuous
variables and the v2 test for categorical variables):
*p<0.05, **p<0.005.
MET: metabolic equivalent.

Table 2. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected nutrient and dietary component intakes
=======================================================
Nutrients Q1 Q2 Q3 p^c for trend
=======================================================
Total energy
Intake range (kcal/d) </=1724 </=2339 and >1724 >2339
Cases/Controls 17/16 22/16 50/16
Univariate OR (95%CI) 1.00 1.29 (0.51-3.31) 2.94 (1.21-7.12)
0.012
Multivariate OR^b (95%CI) 1.17 (0.44-3.13) 2.76 (1.10-7.02)
0.026
Fat
Intake range (g/d) </=57 </=87.7 and >57 >87.7
Cases/Controls 20/16 24/16 45/16
Univariate OR (95%CI) 1.00 1.20 (0.48-2.99) 2.25 (0.94-5.37)
0.06
Multivariate OR (95%CI) 0.82 (0.27-2.47) 1.03 (0.25-4.20) 0.88
Protein
Intake range (g/d) </=61.8 </=88 and >62 >88
Cases/Controls 22/16 23/16 44/16
Univariate OR (95%CI) 1.00 1.04 (0.42-2.59) 2.00 (0.84-4.73) 0.1
Multivariate OR (95%CI) 0.84 (0.30-2.36) 1.05 (0.27-4.05) 0.94
Carbohydrates
Intake range (g/d) </=216.5 </=338.6 and >216.5 >338.6
Cases/Controls 18/16 32/16 39/16
Univariate OR (95%CI) 1.00 1.78 (0.72-4.38) 2.17 (0.89-5.28) 0.1
Multivariate OR (95%CI) 1.28 (0.41-3.96) 0.81 (0.18-3.76) 0.65
PUFAs
Intake range (g/d) </=9.4 </=14,1 and >9.4 >14.1
Cases/Controls 20/16 22/16 47/16
Univariate OR (95%CI) 1.00 1.10 (0.44-2.76) 2.35 (0.99-5.60)
0.04
Multivariate OR (95%CI) 0.92 (0.30-2.82) 1.33 (0.34-0.16) 0.75
MUFAs
Intake range (g/d) </=22.6 </=33.5 and >22.6 >33.6
Cases/Controls 18/16 23/16 48/16
Univariate OR (95%CI) 1.00 1.28 (0.50-3.23) 2.67 (1.11-6.43)
0.02
Multivariate OR (95%CI) 0.99 (0.34-2.86) 1.49 (0.38-5.88) 0.53
SFAs
Intake range (g/d) </=20.4 </=29.2 and >20.4 >29.2
Cases/Controls 21/16 16/16 52/16
Univariate OR (95%CI) 1.00 0.76 (0.30-1.97) 2.48 (1.05-5.84)
0.02
Multivariate OR (95%CI) 0.46 (0.15-1.42) 1.42 (0.43-4.64) 0.36
Alcohol
Intake range (g/d) </=1.7 </=7.9 and >1.7 >7.9
Cases/Controls 30/16 28/17 31/15
Univariate OR (95%CI) 1.00 0.89 (0.37-2.07) 1.10 (0.46-2.62)
0.83
Multivariate OR (95%CI) 0.88 (0.36-2.17) 1.09 (0.44-2.75) 0.87
Beer
Intake range (bottle/wk) 0 </=0.5 and >0.0 >0.5
Cases/Controls 51/23 18/9 20/16
Univariate OR (95%CI) 1.00 0.90 (0.35-2.31) 0.56 (0.25-1.28)
0.19
Multivariate OR (95%CI) 0.95 (0.35-2.59) 0.62 (0.26-1.48) 0.3
Wine
Intake range (5 oz/wk) </=0.3 </=2.0 and >0.3 >2.0
Cases/Controls 41/16 14/13 34/19
Univariate OR (95%CI) 1.00 0.42 (0.16-1.09) 0.70 (0.31-1.56)
0.38
Multivariate OR (95%CI) 0.47 (0.17-1.27) 0.86 (0.36-2.05) 0.67
Spirit
Intake range (5 oz/wk) 0 </=0.7 and >0.0 >0.7
Cases/Controls 61/35 13/7 15/6
Univariate OR (95%CI) 1.00 1.07 (0.39-2.92) 1.43 (0.51-4.03)
0.51
Multivariate OR (95%CI) 1.21 (0.41-3.57) 0.88 (0.29-2.69) 0.92
Vitamin C
Intake range (mg/d) </=166.9 </=310.1 and >166.9 >310.1
Cases/Controls 21/16 31/16 37/16
Univariate OR (95%CI) 1.00 1.48 (0.61-3.58) 1.76 (0.73-4.23)
0.21
Multivariate OR (95%CI) 0.93 (0.34-2.52) 1.19 (0.39-3.57) 0.93
Vitamin E
Intake range (mg/d) </=3.4 </=7.4 and >3.4 >7.4
Cases/Controls 31/16 27/16 31/16
Univariate OR (95%CI) 1.00 0.87 (0.37-2.07) 1.00 (0.43-2.35) 1
Multivariate OR (95%CI) 0.66 (0.24-1.78) 0.59 (0.19-1.79) 0.24
Fibre
Intake range (g/d) </=19.1 </=27.1 and >19.1 >19.1
Cases/Controls 26/16 16/16 47/16
Univariate OR (95%CI) 1.00 0.62 (0.24-1.56) 1.81 (0.78-4.20)
0.13
Multivariate OR (95%CI) 0.51 (0.18-1.41) 1.04 (0.32-3.40) 0.85
Folate
Intake range (mg/d) </=357.6 </=436.9 and >357.6 >436.9
Cases/Controls 29/16 13/16 47/16
Univariate OR (95%CI) 1.00 0.45 (0.17-1.16) 1.62 (0.70-3.73) 0.2
Multivariate OR (95%CI) 0.42 (0.15-1.18) 1.20 (0.41-3.46) 0.9
Caffeine
Intake range (mg/d) </=160.8 </=374.0 and >160.8 >374.0
Cases/Controls 33/16 30/16 26/16
Univariate OR (95%CI) 1.00 0.91 (0.39-2.13) 0.79 (0.32-1.87)
0.59
Multivariate OR (95%CI) 0.67 (0.27-1.68) 0.60 (0.24-1.54) 0.33
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Adjusted for age, maximum lifetime BMI and physical
activity.
c Two-sided Wald test. PUFAs: polyunsaturated fatty
acids; MUFAs:
monounsaturated fatty acids; SFAs: saturated fatty acids.

Table 3. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected lifestyle variables
=======================================================
Variables Q1 Q2 Q3 p^b for trend
=======================================================
BMI at 18
Range (kg/m2) </=19.5 </=21.2 and >19.5 >21.2
Cases/Controls 31/15 30/17 27/15
OR (95%CI) 1.00 1.20 (0.47-3.06) 1.16 (0.46-2.90) 0.71
BMI at 30
Range (kg/m2) </=20.8 </=22.7 and >20.8 >22.7
Cases/Controls 27/15 24/17 37/15
OR (95%CI) 1.00 0.75 (0.30-1.90) 1.24 (0.50-3.10) 0.61
Maximum lifetime BMI
Range (kg/m2) </=23.1 </=25.8 and >23.1 >25.8
Cases/Controls 18/16 27/16 44/16
OR (95%CI) 1.00 0.58 (0.23-1.50) 0.72 (0.30-1.74) 0.25
Age at maximum BMI
Range (years) </=34 </=43 and >34 >43
Cases/Controls 15/16 19/16 54/15
OR (95%CI) 1.00 1.12 (0.41-3.05) 2.90 (1.01-8.36) 0.043
Weight gain since age 18
Range (lbs) </=12 </=35 and >12 >35
Cases/Controls 8/15 35/19 45/13
OR (95%CI) 1.00 3.63 (1.18-11.22) 4.64 (1.52-14.12) 0.011
Weight gain since age 30
Range (lbs) </=8 </=20 and >8 >20
Cases/Controls 9/16 28/14 51/17
OR (95%CI) 1.00 3.43 (1.16-10.14) 4.11 (1.46-11.56) 0.013
Smoking
Range (packs-year) 0 </=14.0 and >0 >14.0
Cases/Controls 45/22 20/11 24/15
OR (95%CI) 1.00 0.86 (0.34-2.21) 0.74 (0.31-1.75) 0.49
Moderate physical activity
Range (MET hours/week) </=11.1 </=24.4 and >11.1 >24.4
Cases/Controls 31/16 15/16 43/16
OR^c (95%CI) 1 0.45 (0.17-1.20) 1.40 (0.58-3.40) 0.4
Vigorous physical activity
Range (MET hours/week) </=0.7 </=9.8 and >0.7 >9.8
Cases/Controls 37/16 33/16 19/16
OR^c (95%CI) 1 1.17 (0.48-2.86) 0.73 (0.27-1.94) 0.56
Total physical activity
Range (MET hours/week) </=17.4 </=35.2 and >17.4 >35.2
Cases/Controls 32/16 25/16 32/15
OR^c (95%CI) 1.00 0.88 (0.35-2.22) 1.05 (0.42-2.60) 0.91
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Two-sided Wald test.
c Adjusted for age, maximum lifetime BMI and total
energy intake. MET:
metabolic equivalent.

... Interestingly, women consuming >2339 kcal/day
were at greater risk of BRCA-related BC compared to
women who consumed <1724 kcal/day, suggesting that
calorie restriction is related to a reduction of BRCArelated
BC risk. This finding was independent of age,
BMI and participation in sports or exercise. There is
consistent evidence from experimental studies indicating
that caloric restriction results in a highly reproducible
and dose-response inhibition of induced BC. Restriction
of energy intake by approximately 30% can reduce
mammary tumors by as much as 90% [20]. A metaanalysis
has shown that energy restriction protects
against the development of mammary tumors in mice,
irrespective of the type of restricted nutrient or other
study characteristics [21]. As well, a number of cohort
studies of calorie restriction tend to support a beneficial
relationship with BC risk. Michels and Ekbom [22]
prospectively followed a cohort of women in Sweden
diagnosed and treated for anorexia before age 40 years
and reported a 50% reduction in BC risk compared to
age-matched controls. Among 4 other cohort studies in
Norway and the Netherlands that focused on the effects
of war-time starvation on BC risk, 2 showed reductions
in risk with exposure to calorie restriction [23,24], 1
found no association [25], and 1 disclosed a positive
association [26]. However, these studies did not gather
information on individual energy intake and did not
account for body size and physical activity. Several
possible mechanisms whereby caloric excess per se
promotes the growth of breast tumors have been proposed.
In general, hormones and other growth factors
are reduced by caloric restriction, and it is logical to
assume that in caloric abundance, tumorigenesis may be
hormone- or growth factor-driven. Disturbances in energy
balance influence BC risk through alterations in the
production of ovarian steroid hormones [27,28], particularly
estradiol that has been shown to be positively
related to BC risk [29]. There is evidence that the effects
of dietary restriction are mediated via changes in the
availability of insulin growth factor-1 that, in turn, inhibit
tumor development by decreasing cell proliferation
[30,31]. A low-calorie diet has been demonstrated to
suppress estrogen secretion under conditions that inhibit
mammary tumor development [32,33]. It has also been
reported that caloric restriction is associated with decreased
free radical production in mitochondria and
with reduced oxidative stress, possibly via lower oxidant
production, enhanced antioxidant capacity, and diminished
inflammation [34,35]. Furthermore, calorie
restriction decreases the DNA replication rate and enhances
the rate of apoptosis, thus reducing tissue susceptibility
to damage by carcinogens [35]. Finally, energy
restriction can reduce reproductive hormones which may
lead to an overall lower lifetime exposure to estrogens.

... In summary, we observed that women with high
energy intake who carry BRCA mutations, regardless of
physical activity and BMI, were at increased BC risk
compared to women with more restricted energy intake.
Weight gain, particularly later in life, is also related to
elevated BRCA-associated BC risk. Further research is
warranted to confirm these associations in other study
populations and hopefully with larger sample sizes.

-- A CRONie, alpater@SHAW.caIt seems that "it has been
suggested that
dietary energy intake restriction may be related to reduced
BRCA-associated
breast cancer (BC) risk" and the paper below (1) reports
that correcting for
caloric intakes and other confounders resulted in no
association with
http://en.wikipedia.org/wiki/Breast_cancer (BC), but did
with BC associated
with http://en.wikipedia.org/wiki/BRCA1 and
http://en.wikipedia.org/wiki/BRCA2 types of BC. Not yet
pdf-availed, is the
paper below (1). The paper was, unfortunately, not a
prospective study.
Unfortunately, also, the (2) paper that is pdf-availed from
the same
research group was also not a prospective study, but a
case-control study.
Much of the same apparently applies to (2), as applied to
(1), regarding the
role of CR.

Nkondjock A, Ghadirian P.
Diet quality and BRCA-associated breast cancer risk.
Breast Cancer Res Treat. 2006 Oct 25; [Epub ahead of print]
PMID: 17063275

Although it has been suggested that dietary energy intake
restriction may be
related to reduced BRCA-associated breast cancer (BC) risk
... Alternate
Healthy Eating Index (AHEI), the Diet Quality Index-Revised
(DQI-R), the
alternate Mediterranean Diet Index (aMED), the Canadian
Healthy Eating Index
(CHEI), and BRCA-associated BC risk, a case-control study
was carried out
within a cohort of 80 French-Canadian families with 250
members involving 89
carriers of BRCA genes affected by BC, 48 non-affected
carriers and 46
non-affected non-carriers. Odds ratios (ORs) and 95%
confidence intervals
(CIs) were calculated in unconditional logistic regression
models. After
adjustment for age, physical activity and total energy
intake, we did not
detect any association between the AHEI or aMED and BC.
However, a strong
and significant inverse relationship was apparent between
the DQI-R and CHEI
and BRCA-associated BC risk. ORs comparing the highest and
lowest tertiles
of diet quality scores were 0.35 (95%CI = 0.12-1.02; p ( )=
0.034 for trend)
for the DQI-R and 0.18 (95%CI = 0.05-0.68; p = 0.006 for
trend) for the
CHEI, respectively. These inverse associations were not the
result of a link
with any specific component of the diet quality indexes.
These results
suggest that dietary guidelines reflected by the DQI-R and
CHEI may
constitute preventive strategies for reducing
BRCA-associated BC risk.

2. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P.
Diet, lifestyle and BRCA-related breast cancer risk among
French-Canadians.
Breast Cancer Res Treat. 2006 Aug;98(3):285-294. Epub 2006
Mar 16.
PMID: 16541324

BACKGROUND: Although the connection between diet, lifestyle
and hormones
suggests that nutritional and lifestyle factors may exert an
influence in
the etiology of breast cancer (BC), it is not clear whether
these factors
operate in the same way in women with BRCA1 and BRCA2 (BRCA)
gene mutations
who already have an elevated BC risk. METHODS: A
case-control study was
conducted within a cohort of 80 French-Canadian families
with 250 members
involving 89 carriers of mutated BRCA gene affected with BC
and 48
non-affected carriers. A validated semi-quantitative food
frequency
questionnaire was used to ascertain dietary intake, and a
lifestyle core
questionnaire, to gather information on physical activity
and other
lifestyle risk factors. Odds ratios (ORs) and 95% confidence
intervals (CIs)
were calculated in unconditional logistic regression models.
RESULTS: After
adjustment for age, maximum lifetime body mass index (BMI)
and physical
activity, a positive association was found between total
energy intake and
BRCA-related BC risk. OR was 2.76 (95%CI: 1.10-7.02; p=0.026
for trend),
when comparing the highest tertile of intake with the
lowest. The intake of
other nutrients and dietary components was not significantly
associated with
the risk of BC. Age at the time the subjects reached maximum
BMI was
significantly related to an elevated BC risk (OR=2.90;
95%CI: 1.01-8.36;
p=0.046 for trend). In addition, a direct and significant
relationship was
noted between maximum weight gain since both age 18 and 30
years and BC
risk. The ORs were 4.64 (95%CI: 1.52-14.12; p=0.011 for
trend) for weight
gain since age 18 years and 4.11 (95%CI: 1.46-11.56; p=0.013
for trend) for
weight gain since age 30 years, respectively. No overall
association was
apparent between BRCA-related BC risk and BMI, smoking, and
physical
activity. CONCLUSION: The results of this preliminary study
suggest that
weight control in adulthood through dietary energy intake
restriction is an
important factor for the prevention of BRCA-related BC risk.

... Germline mutations in the BC susceptibility genes, BRCA1
and BRCA2
(BRCA) are known to cause susceptibility to BC and ovarian
cancer. Compared
with the general population, women who carry BRCA mutations
have a very high
lifetime risk of developing BC. Recent estimates show that
the lifetime risk
of developing BC associated with mutations in either BRCA1
or BRCA2
mutations is extremely high, around 87% by the time the
carriers reach age
70 years [2]. ...

Table 1. Selected characteristics of the study population
=======================================================
Variables Cases (n=89) (%) Controls (n=48) (%)
=======================================================
Age (years, mean±SD) 56.2±11.5 50.9±11.9*
20-29 1 0
30-39 3 13
40-49 27 42
50-59 30 27
60-69 24 10
70-79 13 4
80-89 2 4
Parity
Nulliparous 10 19
=/>1 92 81
Oral contraceptive use
Ever 78 85
Never 22 15
Hormone replacement therapy
Yes 17 26
No 83 74
Marital status
Single 7 6
Married/Common-law 78 75
Separated/Divorced 9 13
Widowed 9 6
Smoking
Ever 44 26
Never 44 22
Type of mutation
BRCA1 39 50
BRCA2 59 50
BRCA1 and BRCA2 2 0
Education attainment (years) 11.9±3.2 12.4±2.9
Age at menarche (years, mean±SD) 12.8±1.6 13.2±1.6
Age at menopause (years, mean±SD) 44.2±6.5 42.5±7.1
Smoking (packs-year, mean±SD) 13.9±21.0 14.7±19.7
Age at maximum weight (lbs, mean±SD) 46.2±13.3 38.8±13.3**
Weight at 18 (lbs, mean±SD) 116.6±14.6 118.8±14.4
Weight at 30 (lbs, mean ± SD) 129.9±21.9 127.4±15.7
Weight at 50 (lbs, mean ± SD) 141.6±27.5 137.3±22.7
Maximum lifetime weight (lbs, mean±SD) 156.4±30.6 145.2±21.9*
Weight gain since age 18 (lbs, mean±SD) 39.8±25.2 26.9±19.4**
Weight gain since age 30 (lbs, mean±SD) 26.6±21.0 18.3±15.3*
Physical activity (MET-hours/week, mean ± SD)
Moderate 23.1±16.6 18.9±12.5
Vigorous 7.7±13.2 10.7±15.4
Total 30.8±23.8 29.6±21.9
Fat intake (g, mean±SD) 97±49 78±38*
Total energy intake (kcal, mean±SD) 2589±1142 2167±830*
Fat (%) 33.5±7.2 32.2±7.2
Protein (%) 14.4±2.9 14.5±2.4
Carbohydrate (%) 52.4±8.5 53.0±9.9
Alcohol (%) 2.4±3.4 3.4±4.4
=======================================================
Significantly different from cases (the Student's t-test
for continuous
variables and the v2 test for categorical variables):
*p<0.05, **p<0.005.
MET: metabolic equivalent.

Table 2. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected nutrient and dietary component intakes
=======================================================
Nutrients Q1 Q2 Q3 p^c for trend
=======================================================
Total energy
Intake range (kcal/d) </=1724 </=2339 and >1724 >2339
Cases/Controls 17/16 22/16 50/16
Univariate OR (95%CI) 1.00 1.29 (0.51-3.31) 2.94 (1.21-7.12)
0.012
Multivariate OR^b (95%CI) 1.17 (0.44-3.13) 2.76 (1.10-7.02)
0.026
Fat
Intake range (g/d) </=57 </=87.7 and >57 >87.7
Cases/Controls 20/16 24/16 45/16
Univariate OR (95%CI) 1.00 1.20 (0.48-2.99) 2.25 (0.94-5.37)
0.06
Multivariate OR (95%CI) 0.82 (0.27-2.47) 1.03 (0.25-4.20) 0.88
Protein
Intake range (g/d) </=61.8 </=88 and >62 >88
Cases/Controls 22/16 23/16 44/16
Univariate OR (95%CI) 1.00 1.04 (0.42-2.59) 2.00 (0.84-4.73) 0.1
Multivariate OR (95%CI) 0.84 (0.30-2.36) 1.05 (0.27-4.05) 0.94
Carbohydrates
Intake range (g/d) </=216.5 </=338.6 and >216.5 >338.6
Cases/Controls 18/16 32/16 39/16
Univariate OR (95%CI) 1.00 1.78 (0.72-4.38) 2.17 (0.89-5.28) 0.1
Multivariate OR (95%CI) 1.28 (0.41-3.96) 0.81 (0.18-3.76) 0.65
PUFAs
Intake range (g/d) </=9.4 </=14,1 and >9.4 >14.1
Cases/Controls 20/16 22/16 47/16
Univariate OR (95%CI) 1.00 1.10 (0.44-2.76) 2.35 (0.99-5.60)
0.04
Multivariate OR (95%CI) 0.92 (0.30-2.82) 1.33 (0.34-0.16) 0.75
MUFAs
Intake range (g/d) </=22.6 </=33.5 and >22.6 >33.6
Cases/Controls 18/16 23/16 48/16
Univariate OR (95%CI) 1.00 1.28 (0.50-3.23) 2.67 (1.11-6.43)
0.02
Multivariate OR (95%CI) 0.99 (0.34-2.86) 1.49 (0.38-5.88) 0.53
SFAs
Intake range (g/d) </=20.4 </=29.2 and >20.4 >29.2
Cases/Controls 21/16 16/16 52/16
Univariate OR (95%CI) 1.00 0.76 (0.30-1.97) 2.48 (1.05-5.84)
0.02
Multivariate OR (95%CI) 0.46 (0.15-1.42) 1.42 (0.43-4.64) 0.36
Alcohol
Intake range (g/d) </=1.7 </=7.9 and >1.7 >7.9
Cases/Controls 30/16 28/17 31/15
Univariate OR (95%CI) 1.00 0.89 (0.37-2.07) 1.10 (0.46-2.62)
0.83
Multivariate OR (95%CI) 0.88 (0.36-2.17) 1.09 (0.44-2.75) 0.87
Beer
Intake range (bottle/wk) 0 </=0.5 and >0.0 >0.5
Cases/Controls 51/23 18/9 20/16
Univariate OR (95%CI) 1.00 0.90 (0.35-2.31) 0.56 (0.25-1.28)
0.19
Multivariate OR (95%CI) 0.95 (0.35-2.59) 0.62 (0.26-1.48) 0.3
Wine
Intake range (5 oz/wk) </=0.3 </=2.0 and >0.3 >2.0
Cases/Controls 41/16 14/13 34/19
Univariate OR (95%CI) 1.00 0.42 (0.16-1.09) 0.70 (0.31-1.56)
0.38
Multivariate OR (95%CI) 0.47 (0.17-1.27) 0.86 (0.36-2.05) 0.67
Spirit
Intake range (5 oz/wk) 0 </=0.7 and >0.0 >0.7
Cases/Controls 61/35 13/7 15/6
Univariate OR (95%CI) 1.00 1.07 (0.39-2.92) 1.43 (0.51-4.03)
0.51
Multivariate OR (95%CI) 1.21 (0.41-3.57) 0.88 (0.29-2.69) 0.92
Vitamin C
Intake range (mg/d) </=166.9 </=310.1 and >166.9 >310.1
Cases/Controls 21/16 31/16 37/16
Univariate OR (95%CI) 1.00 1.48 (0.61-3.58) 1.76 (0.73-4.23)
0.21
Multivariate OR (95%CI) 0.93 (0.34-2.52) 1.19 (0.39-3.57) 0.93
Vitamin E
Intake range (mg/d) </=3.4 </=7.4 and >3.4 >7.4
Cases/Controls 31/16 27/16 31/16
Univariate OR (95%CI) 1.00 0.87 (0.37-2.07) 1.00 (0.43-2.35) 1
Multivariate OR (95%CI) 0.66 (0.24-1.78) 0.59 (0.19-1.79) 0.24
Fibre
Intake range (g/d) </=19.1 </=27.1 and >19.1 >19.1
Cases/Controls 26/16 16/16 47/16
Univariate OR (95%CI) 1.00 0.62 (0.24-1.56) 1.81 (0.78-4.20)
0.13
Multivariate OR (95%CI) 0.51 (0.18-1.41) 1.04 (0.32-3.40) 0.85
Folate
Intake range (mg/d) </=357.6 </=436.9 and >357.6 >436.9
Cases/Controls 29/16 13/16 47/16
Univariate OR (95%CI) 1.00 0.45 (0.17-1.16) 1.62 (0.70-3.73) 0.2
Multivariate OR (95%CI) 0.42 (0.15-1.18) 1.20 (0.41-3.46) 0.9
Caffeine
Intake range (mg/d) </=160.8 </=374.0 and >160.8 >374.0
Cases/Controls 33/16 30/16 26/16
Univariate OR (95%CI) 1.00 0.91 (0.39-2.13) 0.79 (0.32-1.87)
0.59
Multivariate OR (95%CI) 0.67 (0.27-1.68) 0.60 (0.24-1.54) 0.33
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Adjusted for age, maximum lifetime BMI and physical
activity.
c Two-sided Wald test. PUFAs: polyunsaturated fatty
acids; MUFAs:
monounsaturated fatty acids; SFAs: saturated fatty acids.

Table 3. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected lifestyle variables
=======================================================
Variables Q1 Q2 Q3 p^b for trend
=======================================================
BMI at 18
Range (kg/m2) </=19.5 </=21.2 and >19.5 >21.2
Cases/Controls 31/15 30/17 27/15
OR (95%CI) 1.00 1.20 (0.47-3.06) 1.16 (0.46-2.90) 0.71
BMI at 30
Range (kg/m2) </=20.8 </=22.7 and >20.8 >22.7
Cases/Controls 27/15 24/17 37/15
OR (95%CI) 1.00 0.75 (0.30-1.90) 1.24 (0.50-3.10) 0.61
Maximum lifetime BMI
Range (kg/m2) </=23.1 </=25.8 and >23.1 >25.8
Cases/Controls 18/16 27/16 44/16
OR (95%CI) 1.00 0.58 (0.23-1.50) 0.72 (0.30-1.74) 0.25
Age at maximum BMI
Range (years) </=34 </=43 and >34 >43
Cases/Controls 15/16 19/16 54/15
OR (95%CI) 1.00 1.12 (0.41-3.05) 2.90 (1.01-8.36) 0.043
Weight gain since age 18
Range (lbs) </=12 </=35 and >12 >35
Cases/Controls 8/15 35/19 45/13
OR (95%CI) 1.00 3.63 (1.18-11.22) 4.64 (1.52-14.12) 0.011
Weight gain since age 30
Range (lbs) </=8 </=20 and >8 >20
Cases/Controls 9/16 28/14 51/17
OR (95%CI) 1.00 3.43 (1.16-10.14) 4.11 (1.46-11.56) 0.013
Smoking
Range (packs-year) 0 </=14.0 and >0 >14.0
Cases/Controls 45/22 20/11 24/15
OR (95%CI) 1.00 0.86 (0.34-2.21) 0.74 (0.31-1.75) 0.49
Moderate physical activity
Range (MET hours/week) </=11.1 </=24.4 and >11.1 >24.4
Cases/Controls 31/16 15/16 43/16
OR^c (95%CI) 1 0.45 (0.17-1.20) 1.40 (0.58-3.40) 0.4
Vigorous physical activity
Range (MET hours/week) </=0.7 </=9.8 and >0.7 >9.8
Cases/Controls 37/16 33/16 19/16
OR^c (95%CI) 1 1.17 (0.48-2.86) 0.73 (0.27-1.94) 0.56
Total physical activity
Range (MET hours/week) </=17.4 </=35.2 and >17.4 >35.2
Cases/Controls 32/16 25/16 32/15
OR^c (95%CI) 1.00 0.88 (0.35-2.22) 1.05 (0.42-2.60) 0.91
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Two-sided Wald test.
c Adjusted for age, maximum lifetime BMI and total
energy intake. MET:
metabolic equivalent.

... Interestingly, women consuming >2339 kcal/day
were at greater risk of BRCA-related BC compared to
women who consumed <1724 kcal/day, suggesting that
calorie restriction is related to a reduction of BRCArelated
BC risk. This finding was independent of age,
BMI and participation in sports or exercise. There is
consistent evidence from experimental studies indicating
that caloric restriction results in a highly reproducible
and dose-response inhibition of induced BC. Restriction
of energy intake by approximately 30% can reduce
mammary tumors by as much as 90% [20]. A metaanalysis
has shown that energy restriction protects
against the development of mammary tumors in mice,
irrespective of the type of restricted nutrient or other
study characteristics [21]. As well, a number of cohort
studies of calorie restriction tend to support a beneficial
relationship with BC risk. Michels and Ekbom [22]
prospectively followed a cohort of women in Sweden
diagnosed and treated for anorexia before age 40 years
and reported a 50% reduction in BC risk compared to
age-matched controls. Among 4 other cohort studies in
Norway and the Netherlands that focused on the effects
of war-time starvation on BC risk, 2 showed reductions
in risk with exposure to calorie restriction [23,24], 1
found no association [25], and 1 disclosed a positive
association [26]. However, these studies did not gather
information on individual energy intake and did not
account for body size and physical activity. Several
possible mechanisms whereby caloric excess per se
promotes the growth of breast tumors have been proposed.
In general, hormones and other growth factors
are reduced by caloric restriction, and it is logical to
assume that in caloric abundance, tumorigenesis may be
hormone- or growth factor-driven. Disturbances in energy
balance influence BC risk through alterations in the
production of ovarian steroid hormones [27,28], particularly
estradiol that has been shown to be positively
related to BC risk [29]. There is evidence that the effects
of dietary restriction are mediated via changes in the
availability of insulin growth factor-1 that, in turn, inhibit
tumor development by decreasing cell proliferation
[30,31]. A low-calorie diet has been demonstrated to
suppress estrogen secretion under conditions that inhibit
mammary tumor development [32,33]. It has also been
reported that caloric restriction is associated with decreased
free radical production in mitochondria and
with reduced oxidative stress, possibly via lower oxidant
production, enhanced antioxidant capacity, and diminished
inflammation [34,35]. Furthermore, calorie
restriction decreases the DNA replication rate and enhances
the rate of apoptosis, thus reducing tissue susceptibility
to damage by carcinogens [35]. Finally, energy
restriction can reduce reproductive hormones which may
lead to an overall lower lifetime exposure to estrogens.

... In summary, we observed that women with high
energy intake who carry BRCA mutations, regardless of
physical activity and BMI, were at increased BC risk
compared to women with more restricted energy intake.
Weight gain, particularly later in life, is also related to
elevated BRCA-associated BC risk. Further research is
warranted to confirm these associations in other study
populations and hopefully with larger sample sizes.

-- A CRONie, alpater@SHAW.caIt seems that "it has been
suggested that
dietary energy intake restriction may be related to reduced
BRCA-associated
breast cancer (BC) risk" and the paper below (1) reports
that correcting for
caloric intakes and other confounders resulted in no
association with
http://en.wikipedia.org/wiki/Breast_cancer (BC), but did
with BC associated
with http://en.wikipedia.org/wiki/BRCA1 and
http://en.wikipedia.org/wiki/BRCA2 types of BC. Not yet
pdf-availed, is the
paper below (1). The paper was, unfortunately, not a
prospective study.
Unfortunately, also, the (2) paper that is pdf-availed from
the same
research group was also not a prospective study, but a
case-control study.
Much of the same apparently applies to (2), as applied to
(1), regarding the
role of CR.

Nkondjock A, Ghadirian P.
Diet quality and BRCA-associated breast cancer risk.
Breast Cancer Res Treat. 2006 Oct 25; [Epub ahead of print]
PMID: 17063275

Although it has been suggested that dietary energy intake
restriction may be
related to reduced BRCA-associated breast cancer (BC) risk
... Alternate
Healthy Eating Index (AHEI), the Diet Quality Index-Revised
(DQI-R), the
alternate Mediterranean Diet Index (aMED), the Canadian
Healthy Eating Index
(CHEI), and BRCA-associated BC risk, a case-control study
was carried out
within a cohort of 80 French-Canadian families with 250
members involving 89
carriers of BRCA genes affected by BC, 48 non-affected
carriers and 46
non-affected non-carriers. Odds ratios (ORs) and 95%
confidence intervals
(CIs) were calculated in unconditional logistic regression
models. After
adjustment for age, physical activity and total energy
intake, we did not
detect any association between the AHEI or aMED and BC.
However, a strong
and significant inverse relationship was apparent between
the DQI-R and CHEI
and BRCA-associated BC risk. ORs comparing the highest and
lowest tertiles
of diet quality scores were 0.35 (95%CI = 0.12-1.02; p ( )=
0.034 for trend)
for the DQI-R and 0.18 (95%CI = 0.05-0.68; p = 0.006 for
trend) for the
CHEI, respectively. These inverse associations were not the
result of a link
with any specific component of the diet quality indexes.
These results
suggest that dietary guidelines reflected by the DQI-R and
CHEI may
constitute preventive strategies for reducing
BRCA-associated BC risk.

2. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P.
Diet, lifestyle and BRCA-related breast cancer risk among
French-Canadians.
Breast Cancer Res Treat. 2006 Aug;98(3):285-294. Epub 2006
Mar 16.
PMID: 16541324

BACKGROUND: Although the connection between diet, lifestyle
and hormones
suggests that nutritional and lifestyle factors may exert an
influence in
the etiology of breast cancer (BC), it is not clear whether
these factors
operate in the same way in women with BRCA1 and BRCA2 (BRCA)
gene mutations
who already have an elevated BC risk. METHODS: A
case-control study was
conducted within a cohort of 80 French-Canadian families
with 250 members
involving 89 carriers of mutated BRCA gene affected with BC
and 48
non-affected carriers. A validated semi-quantitative food
frequency
questionnaire was used to ascertain dietary intake, and a
lifestyle core
questionnaire, to gather information on physical activity
and other
lifestyle risk factors. Odds ratios (ORs) and 95% confidence
intervals (CIs)
were calculated in unconditional logistic regression models.
RESULTS: After
adjustment for age, maximum lifetime body mass index (BMI)
and physical
activity, a positive association was found between total
energy intake and
BRCA-related BC risk. OR was 2.76 (95%CI: 1.10-7.02; p=0.026
for trend),
when comparing the highest tertile of intake with the
lowest. The intake of
other nutrients and dietary components was not significantly
associated with
the risk of BC. Age at the time the subjects reached maximum
BMI was
significantly related to an elevated BC risk (OR=2.90;
95%CI: 1.01-8.36;
p=0.046 for trend). In addition, a direct and significant
relationship was
noted between maximum weight gain since both age 18 and 30
years and BC
risk. The ORs were 4.64 (95%CI: 1.52-14.12; p=0.011 for
trend) for weight
gain since age 18 years and 4.11 (95%CI: 1.46-11.56; p=0.013
for trend) for
weight gain since age 30 years, respectively. No overall
association was
apparent between BRCA-related BC risk and BMI, smoking, and
physical
activity. CONCLUSION: The results of this preliminary study
suggest that
weight control in adulthood through dietary energy intake
restriction is an
important factor for the prevention of BRCA-related BC risk.

... Germline mutations in the BC susceptibility genes, BRCA1
and BRCA2
(BRCA) are known to cause susceptibility to BC and ovarian
cancer. Compared
with the general population, women who carry BRCA mutations
have a very high
lifetime risk of developing BC. Recent estimates show that
the lifetime risk
of developing BC associated with mutations in either BRCA1
or BRCA2
mutations is extremely high, around 87% by the time the
carriers reach age
70 years [2]. ...

Table 1. Selected characteristics of the study population
=======================================================
Variables Cases (n=89) (%) Controls (n=48) (%)
=======================================================
Age (years, mean±SD) 56.2±11.5 50.9±11.9*
20-29 1 0
30-39 3 13
40-49 27 42
50-59 30 27
60-69 24 10
70-79 13 4
80-89 2 4
Parity
Nulliparous 10 19
=/>1 92 81
Oral contraceptive use
Ever 78 85
Never 22 15
Hormone replacement therapy
Yes 17 26
No 83 74
Marital status
Single 7 6
Married/Common-law 78 75
Separated/Divorced 9 13
Widowed 9 6
Smoking
Ever 44 26
Never 44 22
Type of mutation
BRCA1 39 50
BRCA2 59 50
BRCA1 and BRCA2 2 0
Education attainment (years) 11.9±3.2 12.4±2.9
Age at menarche (years, mean±SD) 12.8±1.6 13.2±1.6
Age at menopause (years, mean±SD) 44.2±6.5 42.5±7.1
Smoking (packs-year, mean±SD) 13.9±21.0 14.7±19.7
Age at maximum weight (lbs, mean±SD) 46.2±13.3 38.8±13.3**
Weight at 18 (lbs, mean±SD) 116.6±14.6 118.8±14.4
Weight at 30 (lbs, mean ± SD) 129.9±21.9 127.4±15.7
Weight at 50 (lbs, mean ± SD) 141.6±27.5 137.3±22.7
Maximum lifetime weight (lbs, mean±SD) 156.4±30.6 145.2±21.9*
Weight gain since age 18 (lbs, mean±SD) 39.8±25.2 26.9±19.4**
Weight gain since age 30 (lbs, mean±SD) 26.6±21.0 18.3±15.3*
Physical activity (MET-hours/week, mean ± SD)
Moderate 23.1±16.6 18.9±12.5
Vigorous 7.7±13.2 10.7±15.4
Total 30.8±23.8 29.6±21.9
Fat intake (g, mean±SD) 97±49 78±38*
Total energy intake (kcal, mean±SD) 2589±1142 2167±830*
Fat (%) 33.5±7.2 32.2±7.2
Protein (%) 14.4±2.9 14.5±2.4
Carbohydrate (%) 52.4±8.5 53.0±9.9
Alcohol (%) 2.4±3.4 3.4±4.4
=======================================================
Significantly different from cases (the Student's t-test
for continuous
variables and the v2 test for categorical variables):
*p<0.05, **p<0.005.
MET: metabolic equivalent.

Table 2. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected nutrient and dietary component intakes
=======================================================
Nutrients Q1 Q2 Q3 p^c for trend
=======================================================
Total energy
Intake range (kcal/d) </=1724 </=2339 and >1724 >2339
Cases/Controls 17/16 22/16 50/16
Univariate OR (95%CI) 1.00 1.29 (0.51-3.31) 2.94 (1.21-7.12)
0.012
Multivariate OR^b (95%CI) 1.17 (0.44-3.13) 2.76 (1.10-7.02)
0.026
Fat
Intake range (g/d) </=57 </=87.7 and >57 >87.7
Cases/Controls 20/16 24/16 45/16
Univariate OR (95%CI) 1.00 1.20 (0.48-2.99) 2.25 (0.94-5.37)
0.06
Multivariate OR (95%CI) 0.82 (0.27-2.47) 1.03 (0.25-4.20) 0.88
Protein
Intake range (g/d) </=61.8 </=88 and >62 >88
Cases/Controls 22/16 23/16 44/16
Univariate OR (95%CI) 1.00 1.04 (0.42-2.59) 2.00 (0.84-4.73) 0.1
Multivariate OR (95%CI) 0.84 (0.30-2.36) 1.05 (0.27-4.05) 0.94
Carbohydrates
Intake range (g/d) </=216.5 </=338.6 and >216.5 >338.6
Cases/Controls 18/16 32/16 39/16
Univariate OR (95%CI) 1.00 1.78 (0.72-4.38) 2.17 (0.89-5.28) 0.1
Multivariate OR (95%CI) 1.28 (0.41-3.96) 0.81 (0.18-3.76) 0.65
PUFAs
Intake range (g/d) </=9.4 </=14,1 and >9.4 >14.1
Cases/Controls 20/16 22/16 47/16
Univariate OR (95%CI) 1.00 1.10 (0.44-2.76) 2.35 (0.99-5.60)
0.04
Multivariate OR (95%CI) 0.92 (0.30-2.82) 1.33 (0.34-0.16) 0.75
MUFAs
Intake range (g/d) </=22.6 </=33.5 and >22.6 >33.6
Cases/Controls 18/16 23/16 48/16
Univariate OR (95%CI) 1.00 1.28 (0.50-3.23) 2.67 (1.11-6.43)
0.02
Multivariate OR (95%CI) 0.99 (0.34-2.86) 1.49 (0.38-5.88) 0.53
SFAs
Intake range (g/d) </=20.4 </=29.2 and >20.4 >29.2
Cases/Controls 21/16 16/16 52/16
Univariate OR (95%CI) 1.00 0.76 (0.30-1.97) 2.48 (1.05-5.84)
0.02
Multivariate OR (95%CI) 0.46 (0.15-1.42) 1.42 (0.43-4.64) 0.36
Alcohol
Intake range (g/d) </=1.7 </=7.9 and >1.7 >7.9
Cases/Controls 30/16 28/17 31/15
Univariate OR (95%CI) 1.00 0.89 (0.37-2.07) 1.10 (0.46-2.62)
0.83
Multivariate OR (95%CI) 0.88 (0.36-2.17) 1.09 (0.44-2.75) 0.87
Beer
Intake range (bottle/wk) 0 </=0.5 and >0.0 >0.5
Cases/Controls 51/23 18/9 20/16
Univariate OR (95%CI) 1.00 0.90 (0.35-2.31) 0.56 (0.25-1.28)
0.19
Multivariate OR (95%CI) 0.95 (0.35-2.59) 0.62 (0.26-1.48) 0.3
Wine
Intake range (5 oz/wk) </=0.3 </=2.0 and >0.3 >2.0
Cases/Controls 41/16 14/13 34/19
Univariate OR (95%CI) 1.00 0.42 (0.16-1.09) 0.70 (0.31-1.56)
0.38
Multivariate OR (95%CI) 0.47 (0.17-1.27) 0.86 (0.36-2.05) 0.67
Spirit
Intake range (5 oz/wk) 0 </=0.7 and >0.0 >0.7
Cases/Controls 61/35 13/7 15/6
Univariate OR (95%CI) 1.00 1.07 (0.39-2.92) 1.43 (0.51-4.03)
0.51
Multivariate OR (95%CI) 1.21 (0.41-3.57) 0.88 (0.29-2.69) 0.92
Vitamin C
Intake range (mg/d) </=166.9 </=310.1 and >166.9 >310.1
Cases/Controls 21/16 31/16 37/16
Univariate OR (95%CI) 1.00 1.48 (0.61-3.58) 1.76 (0.73-4.23)
0.21
Multivariate OR (95%CI) 0.93 (0.34-2.52) 1.19 (0.39-3.57) 0.93
Vitamin E
Intake range (mg/d) </=3.4 </=7.4 and >3.4 >7.4
Cases/Controls 31/16 27/16 31/16
Univariate OR (95%CI) 1.00 0.87 (0.37-2.07) 1.00 (0.43-2.35) 1
Multivariate OR (95%CI) 0.66 (0.24-1.78) 0.59 (0.19-1.79) 0.24
Fibre
Intake range (g/d) </=19.1 </=27.1 and >19.1 >19.1
Cases/Controls 26/16 16/16 47/16
Univariate OR (95%CI) 1.00 0.62 (0.24-1.56) 1.81 (0.78-4.20)
0.13
Multivariate OR (95%CI) 0.51 (0.18-1.41) 1.04 (0.32-3.40) 0.85
Folate
Intake range (mg/d) </=357.6 </=436.9 and >357.6 >436.9
Cases/Controls 29/16 13/16 47/16
Univariate OR (95%CI) 1.00 0.45 (0.17-1.16) 1.62 (0.70-3.73) 0.2
Multivariate OR (95%CI) 0.42 (0.15-1.18) 1.20 (0.41-3.46) 0.9
Caffeine
Intake range (mg/d) </=160.8 </=374.0 and >160.8 >374.0
Cases/Controls 33/16 30/16 26/16
Univariate OR (95%CI) 1.00 0.91 (0.39-2.13) 0.79 (0.32-1.87)
0.59
Multivariate OR (95%CI) 0.67 (0.27-1.68) 0.60 (0.24-1.54) 0.33
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Adjusted for age, maximum lifetime BMI and physical
activity.
c Two-sided Wald test. PUFAs: polyunsaturated fatty
acids; MUFAs:
monounsaturated fatty acids; SFAs: saturated fatty acids.

Table 3. OR^a and 95%CI for BRCA-related breast cancer
associated with
selected lifestyle variables
=======================================================
Variables Q1 Q2 Q3 p^b for trend
=======================================================
BMI at 18
Range (kg/m2) </=19.5 </=21.2 and >19.5 >21.2
Cases/Controls 31/15 30/17 27/15
OR (95%CI) 1.00 1.20 (0.47-3.06) 1.16 (0.46-2.90) 0.71
BMI at 30
Range (kg/m2) </=20.8 </=22.7 and >20.8 >22.7
Cases/Controls 27/15 24/17 37/15
OR (95%CI) 1.00 0.75 (0.30-1.90) 1.24 (0.50-3.10) 0.61
Maximum lifetime BMI
Range (kg/m2) </=23.1 </=25.8 and >23.1 >25.8
Cases/Controls 18/16 27/16 44/16
OR (95%CI) 1.00 0.58 (0.23-1.50) 0.72 (0.30-1.74) 0.25
Age at maximum BMI
Range (years) </=34 </=43 and >34 >43
Cases/Controls 15/16 19/16 54/15
OR (95%CI) 1.00 1.12 (0.41-3.05) 2.90 (1.01-8.36) 0.043
Weight gain since age 18
Range (lbs) </=12 </=35 and >12 >35
Cases/Controls 8/15 35/19 45/13
OR (95%CI) 1.00 3.63 (1.18-11.22) 4.64 (1.52-14.12) 0.011
Weight gain since age 30
Range (lbs) </=8 </=20 and >8 >20
Cases/Controls 9/16 28/14 51/17
OR (95%CI) 1.00 3.43 (1.16-10.14) 4.11 (1.46-11.56) 0.013
Smoking
Range (packs-year) 0 </=14.0 and >0 >14.0
Cases/Controls 45/22 20/11 24/15
OR (95%CI) 1.00 0.86 (0.34-2.21) 0.74 (0.31-1.75) 0.49
Moderate physical activity
Range (MET hours/week) </=11.1 </=24.4 and >11.1 >24.4
Cases/Controls 31/16 15/16 43/16
OR^c (95%CI) 1 0.45 (0.17-1.20) 1.40 (0.58-3.40) 0.4
Vigorous physical activity
Range (MET hours/week) </=0.7 </=9.8 and >0.7 >9.8
Cases/Controls 37/16 33/16 19/16
OR^c (95%CI) 1 1.17 (0.48-2.86) 0.73 (0.27-1.94) 0.56
Total physical activity
Range (MET hours/week) </=17.4 </=35.2 and >17.4 >35.2
Cases/Controls 32/16 25/16 32/15
OR^c (95%CI) 1.00 0.88 (0.35-2.22) 1.05 (0.42-2.60) 0.91
=======================================================
a Adjusted for age, physical activity and total energy
intake.
b Two-sided Wald test.
c Adjusted for age, maximum lifetime BMI and total
energy intake. MET:
metabolic equivalent.

... Interestingly, women consuming >2339 kcal/day
were at greater risk of BRCA-related BC compared to
women who consumed <1724 kcal/day, suggesting that
calorie restriction is related to a reduction of BRCArelated
BC risk. This finding was independent of age,
BMI and participation in sports or exercise. There is
consistent evidence from experimental studies indicating
that caloric restriction results in a highly reproducible
and dose-response inhibition of induced BC. Restriction
of energy intake by approximately 30% can reduce
mammary tumors by as much as 90% [20]. A metaanalysis
has shown that energy restriction protects
against the development of mammary tumors in mice,
irrespective of the type of restricted nutrient or other
study characteristics [21]. As well, a number of cohort
studies of calorie restriction tend to support a beneficial
relationship with BC risk. Michels and Ekbom [22]
prospectively followed a cohort of women in Sweden
diagnosed and treated for anorexia before age 40 years
and reported a 50% reduction in BC risk compared to
age-matched controls. Among 4 other cohort studies in
Norway and the Netherlands that focused on the effects
of war-time starvation on BC risk, 2 showed reductions
in risk with exposure to calorie restriction [23,24], 1
found no association [25], and 1 disclosed a positive
association [26]. However, these studies did not gather
information on individual energy intake and did not
account for body size and physical activity. Several
possible mechanisms whereby caloric excess per se
promotes the growth of breast tumors have been proposed.
In general, hormones and other growth factors
are reduced by caloric restriction, and it is logical to
assume that in caloric abundance, tumorigenesis may be
hormone- or growth factor-driven. Disturbances in energy
balance influence BC risk through alterations in the
production of ovarian steroid hormones [27,28], particularly
estradiol that has been shown to be positively
related to BC risk [29]. There is evidence that the effects
of dietary restriction are mediated via changes in the
availability of insulin growth factor-1 that, in turn, inhibit
tumor development by decreasing cell proliferation
[30,31]. A low-calorie diet has been demonstrated to
suppress estrogen secretion under conditions that inhibit
mammary tumor development [32,33]. It has also been
reported that caloric restriction is associated with decreased
free radical production in mitochondria and
with reduced oxidative stress, possibly via lower oxidant
production, enhanced antioxidant capacity, and diminished
inflammation [34,35]. Furthermore, calorie
restriction decreases the DNA replication rate and enhances
the rate of apoptosis, thus reducing tissue susceptibility
to damage by carcinogens [35]. Finally, energy
restriction can reduce reproductive hormones which may
lead to an overall lower lifetime exposure to estrogens.

... In summary, we observed that women with high
energy intake who carry BRCA mutations, regardless of
physical activity and BMI, were at increased BC risk
compared to women with more restricted energy intake.
Weight gain, particularly later in life, is also related to
elevated BRCA-associated BC risk. Further research is
warranted to confirm these associations in other study
populations and hopefully with larger sample sizes.