Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality.

BACKGROUND: Studies have found that reproductive factors might have a variable effect on the occurrence of breast cancer (BC) according to the existence or not of a family history of BC. The effect of a family history of BC on the risk of BC may also vary according to the age at diagnosis and the degree of kinship. This may confound the relation between familial risk and reproductive factors. A combined analysis was performed to study the interaction between familial risk and reproductive factors according to degree of familiality, age at interview and menopausal status. METHODS: The present analysis included 2948 cases and 4170 controls in seven case-control studies from four countries. The combined relative risks were estimated using a Bayesian random-effects logistic regression model. RESULTS: The main effects of reproductive life factors on the risk of BC are in agreement with previous studies. Two-way interactions between subject's age or menopausal status and a family history of BC were not significant. Although the three-way interaction between age, familial risk and parity was not significant, familial risk seemed to be increased slightly for women with high parity compared with women with low parity in the older age group, and seemed to be slightly decreased for women with high parity compared with women with low parity in younger women. The subject's age also appeared to have an effect on the interaction between familial risk and the age at first childbirth (P = 0.1). CONCLUSIONS: A possible influence of reproductive and menstrual factors on familial risk of BC has been suggested previously and was also evident in the present study. Three-way interactions between age, family history and parity or age at first childbirth might exist and they merit further investigation.

The effects of interaction between familial and reproductive factors on breast cancer risk: a combined analysis of seven case-control studies.

In this paper, a combined analysis was performed to study the interaction between familial risk and reproductive life factors. In particular, the interaction between familial risk and breast cell mitotic activity (BCMA), as assessed by duration of ovarian activity, was investigated because of the potential importance of mitotic activity on genetically susceptible cells. The present analysis included 3152 cases and 4404 controls in seven case-control studies from four countries. The interaction effect was estimated in each study separately, then combined using two different methods: a multivariate weighted average and a Bayesian random-effects model. The main effects of reproductive life factors on the risk of breast cancer were in agreement with the previous findings. In particular, an increased duration of BCMA before the first childbirth and over life was found to increase the risk of breast cancer (P < 0.001). Slightly increasing but non-significant, familial risks were observed with increasing number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and increasing duration of BCMA (P > 0.2). There was no modification in familial risk with age at menarche and no clear pattern with menopause characteristics. A weak influence of reproductive and menstrual factors on the familial risk emerged from the present study.

Familial risk, abortion and their interactive effect on the risk of breast cancer--a combined analysis of six case-control studies.

In a previous study in France, we reported that the relative risk of breast cancer associated with a family history of breast cancer was higher in those subjects with a history of abortions. The present study was undertaken to check the existence of this interaction in other studies and to investigate whether the interaction is modified by the time at which abortions occur. Data were obtained from six case-control studies in France, Australia and Russia, with information on family history of breast cancer and abortion for 2693 breast cancer cases and 3493 controls. The interaction effect was estimated in each study separately, then combined using a multivariate weighted average. The relative risk conferred by a family history of breast cancer increased with the number of abortions (1.8 for no abortion, 1.9 for one abortion, 2.8 for two or more). There was a significant interaction between total number of abortions and family history (P = 0.04), but this was no longer significant when adjusted for other risk factors. The familial risk was highest for those who had had an abortion before first childbirth (1.9 for abortion after first childbirth, 2.7 for abortion before first childbirth). The adjusted risk associated with family history was significantly higher in those with an abortion before first childbirth (P = 0.04). Our findings suggest a synergism between familial factors and abortion. The interaction was not substantially modified by the type of abortion (spontaneous or induced) but was modified by the time at which it occurred in relation to first childbirth. This suggests an effect of abortion itself rather than predisposition to abortion. Further studies of breast cancer cases, particularly among BRCA1 gene carriers and their families, could improve our understanding of this effect.

Endogenous plasma sex hormones in pre- and postmenopausal women with breast cancer: results from a case-control study in Moscow.

Plasma sex hormone-binding globulin (SHBG), testosterone, total oestradiol (E2) and proportion of E2 not bound to blood proteins (percentage free E2) have been measured in a case-control study to test whether any of these factors are related to the risk of breast cancer. The cases studied were 27 premenopausal and 34 postmenopausal women with newly diagnosed localized breast cancer who were admitted to the All-Union Cancer Research Centre, Moscow. The controls were an equivalent number of women from the same neighbourhood. These were matched for age (within 2 years) and menopausal status. The average levels of E2 in cases were significantly higher than controls (p = 0.004 and p < 0.001 for pre- and postmenopausal groups, respectively). Percentage free E2 was significantly raised only in premenopausal cases (p = 0.019). The plasma concentrations of testosterone and SHBG were similar for both pre- and postmenopausal groups. Raised E2 or percentage free E2 was associated with an increased relative risk of breast cancer. However, only E2 levels (crude or adjusted for body build) were significantly related to risk in the two menopausal sets (p = 0.022 and p = 0.002, respectively). High percentage free E2 was associated with almost a threefold increase in the risk of breast cancer in premenopausal women; however, this increase was not statistically significant (p = 0.083). The levels of SHBG or testosterone, crude or adjusted for body build and E2 concentration, were not related to risk of breast cancer.

Diet, alcohol consumption and reproductive factors in a case-control study of breast cancer in Moscow.

A case-control study was conducted in Moscow to assess the effect of diet on risk of breast cancer, and also to study the established reproductive risk factors. A notable finding of the study, which covered 139 case-control pairs matched by age and neighbourhood, is that dietary factors are more important for post-menopausal than for pre-menopausal breast cancer. The decreased risk of post-menopausal breast cancer was associated with high intakes of cellulose (OR 0.04; 95% CI 0.01-0.31), mono- and disaccharides (OR 0.02; 95% CI 0.002-0.27), vitamin C (OR 0.20; 95% CI 0.06-0.70), beta-carotene (OR 0.09; 95% CI 0.02-0.49), and also polyunsaturated fatty acids (OR 0.14; 95% CI 0.03-0.69). High intakes of total fat resulted in a statistically non-significant decrease in the odds ratio (OR 0.52; 95% CI 0.04-6.99), while saturated fats slightly increased the risk of breast cancer (OR 1.67; 95% CI 0.24-11.78). Protein intake was also associated with increased risk of breast cancer (OR 4.62; 95% CI 0.69-30.70). Alcohol use significantly increased the risk of breast cancer in postmenopausal women (OR 3.39; 95% CI 1.37-8.38). In general, the results of our study indicate that high risk of breast cancer is associated with high intakes of nutrients derived from animal products, and low risk with high intake of those from vegetables and fruits.

Fatty acid composition of phospholipids in erythrocyte membranes and risk of breast cancer.

Five fatty acids (FA) 2 saturated, palmitic (C16:0), stearic (C18:0) and 3 unsaturated, oleic (C18:1), linoleic (C18:2), arachidonic (C20:4) acids have been studied in the red cell membranes of breast cancer patients and controls. Statistically significant decrease in the risk of breast cancer has been found to be associated with increase in the levels of linoleic acid in pre-menopausal women and of arachidonic acid in the post-menopausal group.