Linking risk factors and disease origins in breast cancer
Researchers from the Geisel School of Medicine at Dartmouth have found that epigenetic changes to DNA are associated with aging in disease-free breast tissues and are further altered in breast tumors. Epigenetic changes describe heritable alterations caused by mechanisms other than by changes in DNA sequence. The discovery, published in the February 2014 issue of Epigenetics, illustrates how cancer and aging are tightly interconnected processes by identifying epigenetic alterations present in the normal aging breast that may increase disease risk in cancer-free individuals.
The epigenetic changes examined highlight different patterns in DNA methylation, which involves the chemical modification of DNA and acts in the control of gene expression. While DNA methylation is a normal and necessary epigenetic process, breast tumors exhibit altered methylation patterns compared to normal breast tissue. Accordingly, atypical DNA methylation marks are recognized to precede cancer initiation.
For the study, the researchers leveraged publicly available genome-wide methylation data on disease-free breast tissues and identified consistent methylation alterations associated with the aging process across multiple populations. The levels of methylation in normal tissues were then compared to breast tumor tissues where age-related changes were further altered in breast tumors. Their data suggests that there may be common genomic regions that are particularly susceptible to changes in DNA methylation over time in disease-free breast tissue (or that these changes are selected for) on the path to development of cancer.
Although age is the strongest demographic risk factor for breast cancer, the mechanisms underlying how age increases a woman’s risk for the development of disease are incompletely characterized.
Emerging literature has demonstrated that aging can have profound effects on DNA methylation patterns that reflect an accumulation of exposures. Hence, the study extends the understanding of the biological mechanisms through which an established breast cancer risk factor, such as age, contributes to carcinogenesis.
Every woman wants to know what she can do to lower her risk of breast cancer. Some of the factors associated with breast cancer - being a woman, your age, and your genetics, for example - can’t be changed. Other factors - being overweight, lack of exercise, smoking cigarettes, and eating unhealthy food - can be changed by making choices. By choosing the healthiest lifestyle options possible, you can empower yourself and make sure your breast cancer risk is as low as possible.
The known risk factors for breast cancer are listed below. Click on each link to learn more about the risk factor and ways you can minimize it in your own life. If a factor can’t be changed (such as your genetics), you can learn about protective steps you can take that can help keep your risk as low as possible.
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Personal History of Breast Cancer
If you’ve been diagnosed with breast cancer, you’re 3 to 4 times more likely to develop a new cancer in the other breast or a different part of the same breast. This risk is different from the risk of the original cancer coming back (called risk of recurrence).
Radiation to Chest or Face Before Age 30
If you had radiation to the chest to treat another cancer (not breast cancer), such as Hodgkin’s disease or non-Hodgkin’s lymphoma, you have a higher-than-average risk of breast cancer. If you had radiation to the face at an adolescent to treat acne (something that’s no longer done), you are at higher risk of developing breast cancer later in life.
Certain Breast Changes
If you’ve been diagnosed with certain benign (not cancer) breast conditions, you may have a higher risk of breast cancer. There are several types of benign breast conditions that affect breast cancer risk
Race/Ethnicity
White women are slightly more likely to develop breast cancer than African American, Hispanic, and Asian women. But African American women are more likely to develop more aggressive, more advanced-stage breast cancer that is diagnosed at a young age.
Being Overweight
Overweight and obese women have a higher risk of being diagnosed with breast cancer compared to women who maintain a healthy weight, especially after menopause. Being overweight also can increase the risk of the breast cancer coming back (recurrence) in women who have had the disease.
Pregnancy History
Women who haven’t had a full-term pregnancy or have their first child after age 30 have a higher risk of breast cancer compared to women who gave birth before age 30.
Breastfeeding History
Breastfeeding can lower breast cancer risk, especially if a woman breastfeeds for longer than 1 year.
Epigenetics is a multidisciplinary peer-reviewed journal that publishes original research and review articles covering the latest findings about epigenetic mechanisms and their role in diverse biological processes. Established in 1997, Landes Bioscience is an Austin, Texas-based publisher of biology research journals and books.
Previous breast disease
Benign breast disease is a generic term describing all non-malignant breast conditions, some of which carry an increased risk for breast cancer while others do not. Women with proliferative breast disease without atypia have a two-fold increased risk, whilst those with atypical hyperplasia have a more that four-fold increased risk.
Women with a strong family history and nonproliferative breast lesions have a 60% increase in risk of breast cancer, but there is no risk increase for women without a family history. (In this study the criteria for a strong family history includes women with at least one first-degree relative with breast cancer before the age of 50 years or two or more relatives with breast cancer, with at least one being a first-degree relative). Women are more likely to develop breast cancer in the same breast as the benign breast lesion than in the opposite breast.
Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are non-invasive conditions of the breast, which can in some cases develop into invasive cancer. Although women with in situdisease are more likely to develop invasive disease, it is difficult to know which are going to, although it is more likely to occur with high grade than low grade DCIS lesions. Overall, women with a previous in situ tumour have double the risk of invasive breast cancer compared to the general population, higher in the same breast as the carcinoma in situ than in the other breast.
A previous diagnosis of breast cancer raises the risk of developing a second primary breast cancer. Risk ratios vary from a 40% risk increase to almost five-fold risk increase. A recent analysis suggests that a substantial proportion of contralateral breast cancers (CBC) diagnosed within two years of the first breast cancer may be in actual fact tumour spread from the primary breast cancer, and two years may be an appropriate cut-off for separating independent breast cancers from those that have spread from a previous breast cancer. Nonetheless, risk of CBC remains higher two or more years after a primary breast cancer, particularly where the first breast cancer was diagnosed before the age of 40. Risk of CBC is higher for women whose first tumour was hormone-receptor negative compared to those with a previous hormone-receptor-positive tumour, according to a recent study. A recent randomised trial has shown that taking tamoxifen for five years, rather than two, can reduce risk of CBC by 30%.
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Andrew Thompson
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Landes Bioscience