Page 31 Complete Your CE Test Online - Click Here ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2 [140]: ● ● Breast cancer: About 12% of women in the general population will develop breast cancer sometime during their lives [103]. By contrast, 55-65% of women with a harmful BRCA1 mutation and around 45% of women with a harmful BRCA2 mutation will develop breast cancer by age 70 [43,75]. ● ● Ovarian cancer: About 1.3% of women in the general population will develop ovarian cancer sometime during their lives [103]. In contrast, 39% of women who inherit a harmful BRCA1 mutation and 11-17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 [43,75]. Mutations in BRCA1 and BRCA2 account for around 15% of all ovarian cancers [235]. Harmful mutations in BRCA1 and BRCA2 increase the risk of several cancers in addition to breast and ovarian cancer. BRCA1 mutations may increase a woman’s risk of developing fallopian tube and peritoneal cancer [52,91]. Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are also at increased risk of breast cancer [267]. Men with harmful BRCA1 or BRCA2 mutations have a higher risk of prostate cancer, and men and women with BRCA1 or BRCA2 mutations may be at increased risk of pancreatic cancer [120,90]. Who should be tested for BRCA mutations? Because harmful BRCA1 or BRCA2 gene mutations are relatively rare in the general population, mutation testing of individuals who do not have cancer should be performed only when the person’s individual or family history suggests the possible presence of a harmful mutation in BRCA1 and/or BRCA2 [140]. In December 2013, the U.S. Preventive Services Task Force recommended that women who have family members with breast, ovarian, fallopian tube, or peritoneal cancer be evaluated to see if they have a family history that is associated with an increased risk of a harmful mutation in one of these genes [296]. Family history factors that are linked with an increased likelihood of having a harmful mutation in BRCA1 or BRCA2 include [140]: ● ● Breast cancer diagnosed before age 50. ● ● Cancer in both breasts in the same woman. ● ● Both breast and ovarian cancers in either the same woman or the same family. ● ● Multiple breast cancers. ● ● Two or more primary types of BRCA1- or BRCA2-related cancers in a single family member. ● ● Men with breast cancer. ● ● Ashkenazi Jewish ethnicity (i.e. ethnic Jews whose families came from Eastern Europe, which constitute the majority of ethnic Jews in the U.S.). People who meet one or more of the above criteria should be referred to genetic counseling for exploration and informed consent. They will learn about the best way to go about the process, other options, what kinds of results might be returned, and what this might mean before they make the decision for the actual test [140]. Risk reduction for those with a BRCA mutation There are actions, such as surgery or drugs, that people with harmful BRCA mutations can take to reduce their risk of BRCA-related cancers. Prophylactic surgery involves removing as much of the “at- risk” tissue as possible, such as breast and ovarian tissue. Removing the ovaries also reduces the risk of breast cancer in premenopausal women by eliminating a source of hormones that can fuel the growth of some breast cancers. Typically, this can wait until the woman has completed childbearing. Even surgery does not guarantee that cancer will not develop because not all of the at-risk tissue can be removed. Still, research showed that women who underwent bilateral prophylactic salpingo-oophorectomy had a nearly 80% reduction in risk of dying from ovarian cancer, a 56% reduction in risk of dying from breast cancer, and a 77% reduction in risk of dying from any cause [82,91]. Drugs and medications can reduce breast cancer risk Data from three studies suggest that tamoxifen may be able to help lower the risk of breast cancer in BRCA1 and BRCA2 mutation carriers, including the risk of cancer in the opposite breast among women previously diagnosed with breast cancer [111,96,239]. Oral contraceptives are thought to reduce the risk of ovarian cancer by about 50% both in the general population and in women with harmful BRCA1 or BRCA2 mutations [128]. Evidence-based practice: Women with harmful BRCA mutations can reduce their future breast cancer risk with medications and/or surgery [140]. Enhanced screening can reduce mortality risk The addition of MRI of the breasts to the annual mammography can be used to improve early detection of breast cancers and improve outcomes of treatment [12]. People who have BRCA1 or BRCA2 mutations might also want to enroll in clinical trials open to people with these mutations. Genetic disease and colorectal cancer A small percentage (5-10%) of colorectal cancers (CRCs) occur in people with a genetic predisposition, including familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch Syndrome [21]. That small percentage is only because these genetic syndromes are fairly rare. A person with FAP develops hundreds to thousands of polyps starting as early as the teen years, so screening with colonoscopy is started very early. CRC can develop before age 20 and many cancers can develop during the person’s lifetime so that colectomy is sometimes performed to prevent them. The person with FAP is at higher risk of other cancers, especially in the GI tract, but their CRC cancer risk alone is nearly 100% by age 40 [21]. A person with Lynch Syndrome runs a nearly 80% lifetime risk of developing CRC, along with a higher risk of stomach cancer. Women with Lynch Syndrome also have a 50% lifetime risk of endometrial cancer, along with a higher risk of ovarian cancer [62]. Other risk factors for CRC are less important than age, genetics, and family history, but include excessive alcohol use, smoking, diabetes, and obesity. Individuals with Ashkenazi Jewish heritage also have a higher risk of CRC [19]. These risk factors alone do not “bump” a person into the high-risk category, but they can offer opportunities for selecting a preventive type of colorectal cancer screening (see section “Cancer Screening Tests”). Family history Even patients without known or suspected genetic predispositions to cancer may have an elevated risk based on family history. Whether this is in part due to family behaviors or habits, or subtler genetic differences is unclear, but it is possible that either or both play a role [60]. Chronic inflammation Inflammation is a normal physiological response that causes injured tissue to heal. An inflammatory process starts when chemicals are released by damaged tissue. In response, white blood cells make and release substances that cause cells to divide and rebuild tissue to help repair the injury. Once the wound is healed, the inflammatory process ends [154]. In chronic inflammation, the inflammatory process may begin even if there is no injury, and it does not end when it should. Why the