Some studies claim that the relationship between alcohol consumption
and breast cancer is linear (Bowlin et al. 1997, Smith-Warner
et al. 1998), but this is challenged y by Zhang et al. (1999),
who conclude from The Framingham Study, that the light to moderate consumption of alcohol is not associated
with an increased risk of breast cancer. It has also been suggested,
but not substantiated, that there is a positive relationship between
the duration (and hence accumulated amount) of alcohol consumption
over the lifespan of a woman and her risk of breast cancer, although
age at commencement of alcohol consumption appears to be irrelevant.
The errantry of the data suggests that causation of breast cancer
may be multi-factorial. The primary risk factors for breast cancer
are purported to be: lifestyle; family history; medical history;
nulliparity;endogenous/exogenous hormones (such as hormone replacement
therapy); body mass index; and environmental exposure to carcinogens.
It has been proposed that alcohol may modify the significance
of these risk factors, andin particular, act additively with those
risk factors that influence the concentration of hormones in plasma.
It has also been proposed that the factors other than family history,
may act additively with the family history risk factor, and also,
that some of these risk factors may be limited to those women
who have a positive family history of breast cancer (Gapstur et
al. 1992). Consequently, it has been proposed that the positive
association between alcohol and breast cancer may be restricted
primarily to women who have a positive family history of breast
cancer.
An elevated concentration of testosterone or estradiol increases
the risk of breast cancer six- and five-fold, respectively, in
both pre and post menopausal women. The concentration of DHEA
sulfate, testosterone and estradiol increased across the menstrual
cycle following the consumption of alcohol (Muti et al. 1997);
and the increase in sulphated DHEA implies that alcohol may also
increase the production of DHEA sulfate in the adrenal cortex.
Hankinsonet al. (1995) also reported an increase in the plasma
concentration of estrone, which is purported to be a primary source
of estradiol in breast cancer cells, following the consumption
of alcohol. Furthermore, the effect of alcohol on the sex hormones
is both acute and chronic.
The data also shows that there is a dose dependent response to
alcohol on the aromatization of testosterone and on the subsequent
concentration of estradiol in plasma, which then peaked and plateaued
(Longnecker et al.1995); this was consistent with the risk of
breast cancer in consumers of alcohol compared to abstainers (Longnecker
et al. 1988).
The question is the level of moderate consumption at which the
elevation of risk occurs, and then relative risk (risk benefit
ratio) when compared with other causes of death, such as cardiovascular
disease, which increases in post-menopausal women. For example,
estrogens significantly lower the concentration of cholesterol
in plasma which is positively associated with a decreased risk
of mortality from cardiovascular disease.
It has been suggested that the use of ERT per se increases the
risk of breast cancer, although the data is inconsistent and hence
inconclusive. The suggestion of a further increased risk of breast
cancer by post-menopausal woman who use ERT and who are also light
to moderate consumers of alcohol remains controversial, in particular
as ERT decreases the risk of other diseases such as cardiovascular
disease, osteoporosis and potentially Alzheimer’s disease and
hence decreases the risk of death from all causes.
Concerning biological or environmental exposure, alcohol is purported
to influence the local and systemic metabolism of mammary carcinogens.
It is suggested that approximately 50% of breast cancer is not
related to genetic/hormonal risk factors, but is related to the
environmental risk. With respect to environmental exposure to
carcinogens, metabolism in the body may either activate or detoxify
the carcinogen. For example:
carcinogen –> toxic intermediates –> detoxified –>excreted??cytochrome
P450 enzymesDNA damage –> cancer. Whereby, a decrease in or inhibition
of metabolism, increases the exposure of the circulating carcinogen
in the blood to organs/tissues, such as the breast.
Because alcohol is not itself genotoxic and nor tumorigenic in
animals, potential mechanisms for the positive association between
alcohol and breast cancer include the facilitation of carcinogens
into cells, the induction of carcinogen activating enzymes, the
inhibition of DNA repair and the promotion of tumors. Potential
ubiquitous carcinogens include N-Nitrosamines, to which people
are exposed from sources such as tobacco.
N-nitrosamine is metabolized bycytochrome P450 enzymes in the
liver, such that in the presence of alcohol ,this metabolism is
inhibited and the unmetabolized carcinogen circulates in the blood
together with the alcohol. The co-exposure of the carcinogen and
alcohol to tissues has been observed to promote tumours in these
tissues.In addition, cytochrome P450 enzymes have been observed
in animal breast tissue and there is greater expression of these
enzymes in breast tissue tumours compared to normal breast tissue,
such that high concentration of circulating carcinogen may be
activated by the cytochrome P450 enzymes and/or alcohol may induce
the activation of these enyzmes (Anderson et al.1995). These observations
are yet to be confirmed in human breast tissue.
Although animal studies show that alcohol does not initiate or
promote tumorogenesis and may actually decrease the incidence
of tumours, some studies also show that alcohol may effect or
enhance metastasising tumours(Weiss et al. 1995, Swanson et al.
1997), and that this effect is dependent on the stage of alcohol
consumption, that is, pre or post treatment with a carcinogen,
and on the amount of alcohol consumed. While it is unknown what
stage of carcinogenesis is affected by alcohol, recent research
implies that alcohol acts at a late stage of carcinogenesis (Weiss
et al. 1995,Swanson et al. 1997). Indeed, from human breast cancer
cell lines, alcohol is observed to selectively stimulate ER+,
but not ER-,estrogen receptors,whereby cancer cells proliferate;
this is one suggested aetiology for breast cancer.
Conclusion
