Health Briefs

September 21, 2002

Breast Tissue Density & Inheritance

Women with extremely dense breast tissue, as determined by mammography, are at increased risk of developing breast cancer.  In this week’s New England Journal of Medicine is a study of breast tissue density among pairs of adult monozygotic (identical) twin women and dizygotic (non-identical or fraternal) twin women.  A total of 571 pairs of monozygotic twins and 380 pairs of dizygotic twins from Australia, Canada and the United States were enrolled in the study.  All study participants underwent digital mammograms, and the resulting x-rays were reviewed by a radiologist who was blinded as to the identity of each patient.  When the resulting data was analyzed, the authors determined that genetic factors accounted for 60 percent of breast tissue density characteristics among the Australian twins, 67 percent of the breast tissue density variability among the North American twins, and 63 percent for all twins studied.  This study, therefore, suggests that perhaps as much as 60 percent of the person-to-person variability in breast tissue density is the result of inheritable genetic factors.  As the incidence of breast cancer appears to be higher in women with denser breasts, it will be interesting to see if future studies are able to find a correlation between the as yet undiscovered genes that control breast tissue density and the increased breast cancer risk associated with dense breasts.  Unfortunately, this study did not assess the incidence of breast cancer in either the identical or non-identical pairs of twins.  Such a study, employing the same comparative analysis of identical vs. non-identical twins, would be a logical next step.

BRCA1 Gene Mutation & the Risk of Breast & Non-breast Cancers

The BRCA1 gene mutation has been linked with a significantly increased risk of breast and ovarian cancer.  Two studies related to the BRCA1 gene mutation are featured in the current issue of the Journal of the National Cancer Institute.  The first study, from England, looked at the incidence of cancers other than breast or ovarian cancer in men and women carrying this particular gene mutation.  A total of 11,847 individuals from 699 families with the mutated gene were studied in 30 different centers across Europe and North America.  The authors determined that the BRCA1 gene was associated with a more than two-fold incidence of pancreatic cancer, and a nearly three-fold increase in the incidence of cervical cancer.  Among study participants less than 65 years old, there was a nearly two-fold increase in the risk of prostate cancer, although this prostate cancer risk increase was not seen in patients older than 65 years.  When the researchers looked at the effect of gender on cancer risks, they found that, overall, women experienced a greater than two-fold increase in the risk of cancers of organs other than the breast or ovary due to the presence of the BRCA1 gene mutation.  However, men did not experience any overall significantly increased risk of such cancers.  This study points to the widespread cancer-inducing effects of the mutated BRCA1 gene on multiple organs in the body, in addition to the previously known increased risk of breast and ovarian cancer associated with this mutation.

A second study in the Journal of the National Cancer Institute looks at BRCA1-associated increases in the risks of breast and ovarian cancer associated with the BRCA1.  The actual increase in the risk of breast and ovarian cancer caused by the BRCA1 gene mutation has been hotly debated for several years now.  This study evaluated 483 BRCA1 gene carriers from 147 affected families.  The authors found that the BRCA1 gene conferred a 73 percent likelihood of breast cancer by age 70, and a 41 percent risk of ovarian cancer by age 70.  The risk of developing a second breast cancer (i.e., following diagnosis and treatment of an initial breast cancer) was about 41 percent.  Other cancers were found to be more common among patients with the BRCA1 mutation, including a three-fold increase in the risk of pancreatic cancer, a two-fold increase in the risk of colon cancer, a four-fold increase in the risk of stomach cancer, and a 120-fold increase in the risk of fallopian tube cancer. 

These two studies, when taken together, greatly add to our understanding of the extent of the BRCA1 gene’s impact on cancer incidence among people who carry this mutation.  Further study of the mechanisms that underlie this mutated gene’s cancer-causing effects is imperative in order to develop effective strategies to blunt the mutation’s adverse health effects.

Risks Associated with Smoking after Heart Attacks

A study in the current issue of the Annals of Internal Medicine looks at the impact of smoking vs. smoking cessation following heart attack, and the risk of recurrent heart attacks.  A total of 2,619 patients experiencing their first heart attack were enrolled into this study, and were followed between 1986 and 1996.  At the time of the initial heart attack, 34 percent of patients were nonsmokers, 36 percent were former smokers, and 31 percent were active smokers.  Among the 808 patients who were active smokers at the time of their initial heart attack, 449 quit tobacco following their heart attack.  When comparing the group of nonsmokers with the patients who quit smoking before their first heart attack, the risk of recurrent heart attack was 17 percent greater among the prior smokers.  The patients who had smoked up until their initial heart attack, and who subsequently quit, had a 51 percent greater chance of experiencing recurrent heart attacks than the patients who never smoked.  Among the patients who quit smoking after their first heart attack, the risk of recurrent heart attack was increased by 62 percent during the first 6 months of smoking cessation.  This relative risk declined to 48 percent with smoking abstinence between 6 and 18 months, and to only 2 percent after 36 or more months of smoking cessation.  Thus, patients who smoke up to—or after—the point at which they experience their first heart attack appear to have a significantly increased risk of a second heart attack when compared to nonsmokers.  However, if smoking is discontinued after the initial heart attack for at least 36 months, then the risk of a second attack falls to approximately the same level as for people who never smoked.  Remember, smoking significantly increases not only the incidence of recurrent heart attacks, but also that of first heart attacks as well!

Dietary Folate & the Risk of Colorectal Cancer

The vitamin folate has previously been linked with a possible reduction in the risk of colorectal cancer.  A new study from The Netherlands, as reported in the current journal Cancer, prospectively studied 120,852 men and women aged 55 to 69 years over a period of more than 7 years.  Colon cancer occurred in 760 of the research subjects, while another 411 patients developed rectal carcinoma.  The entire group was prospectively assessed for the quantity of folate in their diet.  The study concluded that high levels of folate in the diet yielded a 27 percent reduction in colon cancer rates among men, and a 32 percent reduction in women.  Regarding the effects of dietary folate on the risk of rectal cancer, high levels of folate in the diet reduced rectal cancer risks by 34 percent in men.  Curiously, folate did not appear to provide any significant protective effect associated with the risk of rectal cancer in women.

This study adds to the growing evidence that ample folate levels in the diet may be associated with a reduced risk of developing colon cancer.  The apparent gender-related difference in the putative protective effect of folate against rectal cancer is, however, puzzling and suspicious.  Additional studies must, therefore, be done to clarify this incongruous finding.

Dr. Robert A. Wascher