|A Public Service of Mark Kantrowitz|
Breast Cancer Susceptibility Genes (BRCA)
BRCA1 and BRCA2 are tumor suppressor genes involved in the signalling
and repair of DNA damage. The BRCA1 gene was found in 1994 on
the long arm of chromosome 17 and the
BRCA2 gene in 1995 on chromosome 13. Mutations in these genes have
been found in families with hereditary breast cancer and are believed
to predispose carriers to breast, ovarian and other cancers.
The genes were found during studies of hereditary breast cancer in the Ashkenazi Jewish population (Jews of Eastern European descent), but are also found in the rest of the population. The three mutations common in Ashkenazi Jews are BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT). Different ethnic groups may have different mutations. For example, the following are some of the more common mutations in various ethnic groups: BRCA1 (5382insC, C61G and 4153delA) in Polish, BRCA1 (2804delAA) in Dutch, BRCA1 (1081delG) in Chinese, BRCA1 (4153delA, 5382insC) in Russian, and BRCA1 (1832del5, 5296del4) in African-American.
There are several hundred known mutations in these genes, many of which are family-specific. Only the more common alterations have been studied for associations with breast and ovarian cancer. For the others, the significance is not yet apparent.
The prevalence of these genes varies depending on ethnicity. In the Ashkenazi Jewish population, approximately 2.3% to 2.5% of the population has one of the three founder mutations, as shown in the following table. This is 5 to 10 times greater than the prevalence in the general population.
It is possible to have mutations in both the BRCA1 and BRCA2 genes, although this is very rare. The BRCA1 mutations appear to be epistatic with regard to the BRCA2 mutation, meaning that the BRCA1 mutations mask the effect of the BRCA2 mutation. As a result, a woman with both mutations has the same risk of breast cancer as a woman with just a BRCA1 mutation.
The CHEK2 gene was discovered in 1999 on chromsome 22. The 1100delC mutation in this gene was identified as conferring susceptibility to breast cancer in 2002. The mutation is found in about 1.9% of female breast cancer patients compared with 0.7% of controls, yielding an odds ratio of 2.34. The CHEK2 mutation accounts for about 18% of hereditary breast cancer cases. It was also found in 9% of male breast cancer patients, conferring a tenfold increase in risk. The CHEK2 (1100delC) mutation occurs in approximately 1% of the general population. The CHEK2 mutation is suspected of interacting with an as-yet-unidentified gene or genes to increase breast cancer risk. It is also believed to contribute to hereditary prostate cancer risk.
Other genetic mutations associated with increased breast cancer risk include:
Because the BRCA1 and BRCA2 genes were discovered recently, much of the research on cancer risks and cancer prevention is preliminary. There has not yet been sufficient time to evaluate long-term risks thoroughly.
Although only about 7% of breast cancer cases and 34.2% of ovarian cancer cases in Ashkenazi Jewish women are due to the BRCA gene mutations, carriers of these mutations are at much higher risk of breast and ovarian cancer than the general population. (Other studies report that mutations in the BRCA genes account for 5% to 10% of breast cancer cases and 10% of ovarian cancer cases.) The mutations are thought to account for two-thirds (1/2 to 3/4) of hereditary breast cancer cases. Researchers believe that there is another gene, a recessive one, that accounts for hereditary breast cancer in families that do not carry mutations in the BRCA genes.
Statistics on the cancer risk associated with carriers of the BRCA mutations are inconclusive, in part because of the small size and low statistical power of studies so far. Nevertheless, carriers are clearly at significantly increased risk of breast and ovarian cancer.
Depending on the study, women who are carriers of the BRCA mutations have been reported to have a 36%-85% or 76%-87% chance of breast cancer by age 70, compared with a 13.3% chance for non-carriers, and a 16%-60% or 11%-84% chance of ovarian cancer by age 70, compared with a 1.6% to 1.7% chance for non-carriers. (A 35-year-old woman with one relative with ovarian cancer has a 5% lifetime chance of ovarian cancer and a 7% chance with two relatives with ovarian cancer.) Lifetime risks have been estimated at 82%-90% for breast cancer and 23%-54% for ovarian cancer. Carriers have a 20% chance of breast cancer by age 40, 33%-42% by age 50, 55% by age 60, and 80% by age 80. Women with BRCA mutations are more likely to be diagnosed with cancer before age 50 than non-carriers, are less likely to present with stage I disease (27% vs 46%), are more likely to have axillary lymph node involvement (54% vs 46%) and are more likely to have extensive axillary lymph node involvement (25% vs 17%). Although BRCA1 and BRCA2 carriers have a similar lifetime risk of breast cancer, BRCA1 carriers have an earlier age of onset than BRCA2 carriers. BRCA2 carriers have a 32% chance of breast cancer by age 50, 67% chance by age 70, and 80% chance by age 90.
The five year survival rate for BRCA1 carriers is 67%, compared with 77% for BRCA2 carriers, 86% for non-carriers with a family history of breast cancer, and 78% for non-carriers without a family history of breast cancer. However, after adjusting for patient age, cancer stage, and year of diagnosis, there was no significant difference in 5-year survival rates for women with and without a family history of breast cancer.
Women with BRCA mutations are 3.5 times more likely to develop contralateral breast cancer than non-carriers. Another study found that women who are BRCA mutation carriers are much more likely to develop contralateral breast cancer within 5 years than non-carriers (31% vs 4%). Among women with bilateral breast cancer, 29.6% were BRCA mutation carriers, with 18.5% carrying 185delAG, 3.7% carrying 5382insC, and 7.4% carrying 6174delT. The percentage increases to 45% for women with bilateral breast cancer who also have a family history of breast cancer. Among women with bilateral breast cancer whose first tumor was diagnosed before age 42, a total of 82% were carriers of a BRCA mutation, compared with 7.9% for women diagnosed after age 42. This suggests that bilateral breast cancer coupled with early age of onset is a good indication that the patient likely carries a BRCA mutation. Likewise, woman with early onset of breast cancer who carry a BRCA mutation are more likely to develop contralateral breast cancer.
For BRCA1 carriers there is a 40% to 60% lifetime chance of ovarian cancer. For BRCA2 carriers there is a 20% chance of ovarian cancer. A more recent study identified the lifetime risk of ovarian cancer at 63% for BRCA1 carriers and 27% for BRCA2 carriers. Another study found that BRCA mutation carriers have a 7%-9% chance of ovarian cancer by age 50. BRCA carriers tend to get ovarian cancer earlier than non-carriers (50 vs 59 years), and BRCA1 mutation carriers earlier than BRCA2 carriers (48 vs 57 years). The median survival for women with invasive ovarian cancer was 4.5 years for BRCA carriers compared to 3.2 years for non-carriers, with 3-year survival rates of 65.8% and 51.9%, respectively.
A recent large study suggests that the risks of breast and ovarian cancer were overestimated by previous smaller studies, finding a 56% chance of breast cancer by age 70 and a 16% chance of ovarian cancer. Another study estimated the risk for BRCA1 mutation carriers to be 46% by age 70 and 59% by age 80 and for BRCA2 mutation carriers to be 26% at age 70 and 38% at age 80.
Breast cancer progresses faster in women with BRCA1 and BRCA2 mutations than in non-carriers. The tumors and carcinoma in situ also tend to be of higher grade and to show more necrosis in carriers than in non-carriers.
BRCA mutation carriers have a lifetime risk of fallopian tube carcinoma (FTC) of 0.6% and of primary peritoneal carcinoma (PPC) of 1.3%. Approximately 17% of FTC cases and 41% of PPC cases are in patients with BRCA mutations. Mutation carriers have a younger average age at diagnosis than non-carriers (60 years vs 70 years), but a longer median survival (12.3 years vs 3.4 years).
Men who carry the BRCA1 mutation have a 12-18% risk of early-onset prostate cancer.
Men who carry the BRCA2 mutation are at increased risk of prostate cancer and breast cancer. 5.2% of prostate cancer cases had BRCA mutations, compared with 1.9% of controls (i.e., an odds ratio of 3.41). After adjusting for age and stratifying by gene, the odds ratio is 4.78 for men who carry the BRCA2 gene. This means they have almost five times the risk of prostate cancer than men who aren't carriers.
Men who carry the BRCA2 mutation also have a 6% risk of breast cancer by age 70. Other studies have reported a 4% to 14% lifetime risk of developing breast cancer.
Carriers of BRCA2 mutations are also at higher risk of stomach cancer, pancreatic cancer and melanoma.
There is also a suspected link with colorectal cancer, although studies so far have not been able to demonstrate a link. It is possible that the colorectal cancer cases are still hereditary but just not associated with these particular genes.
A study of 58,209 women with breast cancer found that 7.8% of women with one close relative who had developed breast cancer themselves developed breast cancer. For women with two affected relatives, the figure is 13.3%. For women with three affected relatives, the figure is 21.1%. Close relative is defined as a first degree relative (mother, sister, daughter).
Generally, longer exposure to estrogen increases the risk of breast cancer. Women who began menstruating at an early age, who experience late menopause, who never had children, or who took hormone replacement therapy for extended periods of time are at greater risk of breast cancer. Women who had their first child after age 30 are also at increased risk. Women with more dense breast tissue (a high proportion of lobular and ductal tissue) are also at greater risk.
Breast feeding for more than one year reduces the risk of breast cancer in BRCA1 mutation carriers but not in BRCA2 mutation carriers. Previous studies have shown that the relative risk of breast cancer in the general population decreases by 4.3% for every 12 months of breast feeding. There is also a 7% decrease in risk for each child. A 2004 study of 685 BRCA1 women and 280 BRCA2 women found that BRCA1 mutation carriers who breast fed for more than one year had a 44% reduction in the incidence of breast cancer. But the remaining risk of breast cancer was still high, around 40%. There was no decrease in risk for BRCA2 mutation carriers. (Other studies have shown that the risk of breast cancer in BRCA mutation carriers is increased by early parity and the risk increases with the number of pregnancies.) This suggests that the risks associated with the BRCA1 mutation are sensitive to hormone changes while the risks associated with the BRCA2 mutation are not.
Children of a carrier have a 50% chance of inheriting the mutation. So even though men who are carriers face less of a cancer risk than women who are carriers, both can pass on the mutations to their children.
Curiously, carriers of the BRCA1 mutation are more likely to have female children than male children. In carriers of BRCA1 mutations, 67% of children were female, as compared with 54% for BRCA2 and 52% for non-carriers.
Testing for the mutations involves a simple blood test. It typically takes a month for the lab to report results.
The genetic testing is performed by Myriad Genetics, a lab that holds more than a dozen patents on BRCA mutation testing. The cost ranges for $325 for an analysis of a single mutation, to $385 for an analysis of the three mutations found in Ashkenazi Jews, to $2,760 for a full sequencing of the BRCA1 and BRCA2 genes. Individuals who are participating in research studies of hereditary breast and ovarian cancer may be able to be tested by the research study for free. Some health insurance plans will also cover the cost of the test for people with a strong family history of breast and ovarian cancer.
Genetic counseling is required both before and after the test, as interpreting the results can be complicated. The tests look for only a few key mutations, so a negative result does not necessarily eliminate the risk of hereditary breast cancer. The results also need to be interpreted in the context of the family history of cancer, since each mutation carries a different risk of cancer.
For example, if a woman tests negative for the BRCA alterations, but her mother tests positive, then her risk of hereditary breast cancer is reduced. But if her mother also tests negative, then it is unclear whether the hereditary breast cancer risk may be caused by some as-yet-unidentified mutation or other factors, such as a common diet or geographic proximity.
This means that if a woman tests negative for the BRCA mutations, she may need to have her mother and sisters tested before she can interpret the meaning of the result. On the other hand, if a woman tests positive, her mother is most likely a carrier for the mutations, as the mutations do not skip generations.
The tests aren't perfect, so there is a small chance of false negatives. This means that a woman might still carry a deleterious mutation in the BRCA genes even if she tests negative.
Also, not every carrier of the mutations will get breast cancer. It is thought that changes in other genes may modulate the breast cancer risk. Also, external and internal factors, such as lifetime exposure to estrogen, may influence the breast cancer risk. So a woman who tests positive for the mutations needs to consider the incidence rate of breast and ovarian cancer in her family as modifying the overall cancer risks previously reported.
The American Society of Clinical Oncology recommended in 1996 that women with a strong family history of breast cancer or who have an early age of onset of breast cancer be tested for the BRCA mutations. A strong family history is defined as having any of the following:
There are a variety of psychological and social effects that need to be considered.
Carriers of mutations in the BRCA genes face the possibility of discrimination in employment and insurance. For example, some health insurance companies may consider a positive test result to be a pre-existing condition, since a genetic illness exists from birth.
Women who are not currently covered by health insurance or who anticipate a gap in health insurance coverage may wish to delay testing for mutations in the BRCA genes until they have reliable health insurance.
Several states have passed laws barring health insurance companies from discrimination on the basis of genetic testing. A total of 42 states have passed laws prohibiting genetic discrimination in health insurance, and 21 states have passed laws prohibiting genetic discrimination in employment.
On May 21, 2008, the Genetic Information Nondiscrimination Act (GINA) was signed into law (P.L. 110-233). The law prohibits discrimination in group health insurance and employment on the basis of genetic information. It bans group health insurance programs from using genetic information in underwriting; they may not deny coverage based on genetic testing or set premiums based on genetic tests or apply any pre-existing condition exclusions based on genetic tests. The law amends HIPAA to ban disclosure of genetic information, treating genetic information as confidential medical records. The definition of genetic information includes not just individual's genetic tests, but genetic testing of family members. Note that the restrictions on health insurance only apply to group health insurance and not necessarily to individual health insurance. The law bans employment discrimination on the basis of genetic information, including in hiring, discharge and compensation. The law is effective one year after the date of enactment.
Blue Cross/Blue Shield of Nebraska lost a Nebraska Supreme Court case, Katskee v. Blue Cross/Blue Shield of Nebraska, 245 Neb. 808, 515 N.W.2d 645 (Neb. 1994), concerning coverage of prophylactic surgery. The case involved a 43-year-old woman with a strong family history of breast and ovarian cancer who was positive for a BRCA1 mutation. Blue Cross/Blue Shield of Nebraska denied insurance coverage for prophylactic oophorectomy on the grounds that it was not medically necessary because hereditary cancer predisposition did not constitute an illness. The Nebraska Supreme Court found that illness includes an abnormal state resulting from a genetic deviation from the norm, and so contract language dealing with illness applied to patients with a family history of cancer. This case was also discussed in the following paper:
Lynch HT, Severin MJ, Mooney MJ, Lynch J. Insurance adjudication favoring prophylactic surgery in hereditary breast-ovarian cancer syndrome. Gynecol. Oncol. 57(1):23-6, April 1995.
The Women's Health and Cancer Rights Act of 1998 (WHCRA) requires health insurance plans to cover the cost of breast reconstruction after a mastectomy if the insurance plan covered the mastectomy. More information about the Act can be obtained from the US Department of Health and Human Services and the US Department of Labor (FAQ).
Good summaries of legal issues include the following:
Other relevant articles include:
Armstrong K, Weber B, FitzGerald G, Hershey JC, Pauly MV, Lemaire J, Subramanian K, Asch DA. Life Insurance and Breast Cancer risk Assessment: Adverse Selection, Genetic Testing Decisions, and Discrimination. American Journal of Medical Genetics. 120A(3):359-364, July 2003.
There are three main options for treating patients who are carriers of mutations in the BRCA1 and BRCA2 genes: intensive surveillance, chemoprevention, and prophylactic (preventive) surgery.
Prophylactic surgery is more effective at reducing risks in BRCA mutation carriers than chemoprevention, and chemoprevention is more effective than surveillance. Researchers have estimated that prophylactic mastectomy adds 2.9 to 5.3 years of life expectancy for a 30-year-old BRCA mutation carrier when compared with intensive surveillance, and a prophylactic oophorectomy 0.3 to 1.7 years of life expectancy. The benefit is only slightly reduced at age 40, but declines significantly beyond age 40.
According to a UK study by Dr. Klijn of Erasmus University, of women who tested positive for a BRCA1 or BRCA2 mutation, 51% underwent prophylactic mastectomy and 64% underwent prophylactic oophorectomy. Younger women were more likely to undergo a prophylactic mastectomy or prophylactic oophorectomy than older women. Motherhood also strongly influenced the decision to undergo a prophylactic mastectomy (but not a prophylactic oophorectomy), with 61% of women with children choosing a mastectomy compared with 14% of women without children.
According to a study by Dr. Schwartz of Georgetown University, newly diagnosed breast cancer patients who test positive for a BRCA1 or BRCA2 mutation are twice as likely to choose bilateral mastectomy as non-carriers. The risk of developing a second cancer in the contralateral breast is as high as 60%. Of women testing positive, 48% chose a bilateral mastectomy, compared with 24% of non-carriers.
Breast cancer tumors in BRCA carriers may be more responsive to chemotherapy (cisplatin and mitomycin C) and gamma radiation because of the cells inability to repair DNA damage caused by those treatments.
Surveillance includes monthly breast self exams starting at age 18, annual clinical breast exams by a specialist starting at age 25-35 and semi-annual mammograms starting at age 25-35. Women who are not known to be carriers of mutations in the BRCA genes but who have a strong family history of breast cancer should have annual mammograms starting at least 10 years before the earliest onset of breast cancer in her relatives.
Semi-annual mammograms are recommended by a study published in the journal Cancer in 2004. This study found that the majority of breast cancer cases in carriers were found in between annual mammograms, an average of 5.1 months since the last mammogram (range 2-9 months). All of these women had exhibited dense breast tissue in the previous mammogram.
Breast cancer in carriers may mimic benign lesions on the mammogram. So it is important to be screened by an expert and to possibly follow up with ultrasound screening and needle biopsy.
There is a concern, however, that mutations in the BRCA genes may be sensitive to damage from radiation. For example, carriers who are subjected to radiation therapy may be at increased risk of a late second primary breast cancer in the contralateral breast. So some researchers argue that excessive use of X-rays through mammograms should be avoided. They recommend other imaging methods, such as focused ultrasound and breast MRI, that are less likely to induce cellular DNA damage.
Breast MRI may also be more effective at detecting breast cancer in BRCA mutation carriers than mammograms. A study published in the New England Journal of Medicine found that semi-annual clinical breast examination, annual mammography, and annual MRI detected invasive breast cancer in BRCA mutation carriers with a sensitivity of 17.9%, 33.3%, and 79.5%, respectively, and a specificity of 98.1%, 95.0%, and 89.8%. (Sensitivity is the percentage of cancers detected. Specificity is the percentage of positive results that were true positives.) The study also found that the tumors in BRCA mutation carriers were larger than those in non-carriers, suggesting the need for more frequent screening. Because of the lower specificity, more of the results will be uncertain, forcing 2-3 times as many follow-up examinations, diagnostic tests and biopsies. The study did report that mammograms have a higher sensitivity in detecting ductal carcinoma in situ than MRI. A study of 236 Canadian women published in 2004 in JAMA found that breast MRI detected cancer with sensitivity/specificity of 77%/95.4%, compared with 36%/99.8% for mammography, 33%/96% for ultrasound, and 9.1%/99.3% for clinical breast examn. Combining all four screening methods yielded a sensitivity of 95%, compared with 45% for the combination of just mammography and clinical breast exam.
Surveillance for ovarian cancer includes a clinical exam, transvaginal ultrasound and/or Doppler imaging, and blood tests for the CA-125 tumor marker.
Although some researchers question the value of transvaginal ultrasound for the general population, most researchers report that it is a useful screening tool for early detection of ovarian cancer in patients who are BRCA mutation carriers. Use of transvaginal ultrasound for the general population would allow 59% to 65% of ovarian cancers to be diagnosed in stage I with a 7% false positive rate, compared with 5% of unscreened individuals. For BRCA carriers, the sensitivity increases to 88% with a 1% to 3% false positive rate. Early detection results in a 40% reduction in mortality. Accordingly, transvaginal ultrasound is often recommended as a routine screening tool for BRCA carriers but not the general population.
Some researchers recommend measuring the levels of estrogen in blood plasma, although the clinical significance of elevated levels is uncertain.
Some researchers have questioned the effectiveness of surveillance using CA-125 markers and ultrasound in diagnosing early-stage ovarian cancer.
Breast Thermography is a promising imaging technique that may be able to detect breast cancer years before other imaging techniques. Breast cancer causes blood vessels to proliferate, and breast thermography detects the heat generated by the increased circulation. Unfortunately, it cannot pinpoint the location of the cancer.
Chemoprevention involves taking drugs to prevent or delay the onset of breast cancer. The goal is to reduce the risk of breast cancer by reducing "in breast" estrogen levels. Estrogen stimulation is believed to contribute to the promotion of breast cancer.
A study has shown that taking Tamoxifen (Nolvadex) for five years reduces the risk of breast cancer in BRCA mutation carriers by 49%. However, two smaller trials showed little or no reduction in risk (e.g., relative risk of 0.90 for BRCA1 and 0.71 for BRCA2), and it is too soon to judge the impact on long-term mortality. There is also a concern that taking Tamoxifen long-term may cause metastatic uterine cancer (mainly malignant mixed mesodermal tumors, but both carcinoma and sarcoma have been seen), so it should not be taken for more than five years. Stopping Tamoxifen has been reported to result in the appearance of new tumors, so the long-term benefits of Tamoxifen therapy is unclear. (Taking Tamoxifen has a few side benefits, such as reducing cholesterol and increasing bone mineral density in postmenopausal women.)
Tamoxifen is known to be more effective at preventing ER-positive cancers. It may have little or no effect at preventing ER-negative cancers. Women with BRCA1 mutations are more likely to develop ER-negative cancers than non-carriers (70% vs 34%). Carriers of BRCA1 mutations tend to be HER-2/neu negative as well. Women with BRCA2 mutations tend to have an ER/PR profile similar to that of non-carriers, with most tumors ER-positive. The receptor status of relatives with breast cancer should be noted when considering the use of Tamoxifen for chemoprevention in BRCA mutation carriers, as estrogen-insensitive tumors are less likely to respond to hormone therapy.
On the other hand, the expression of the BRCA1 and BRCA2 genes is upregulated during puberty and pregnancy when estrogen levels are significantly increased. This suggests that the expression of these genes might be induced by estrogen, and so exposure to estrogen might affect breast cancer risk.
There is an ongoing study of Raloxifene (Evista) as an alternative to Tamoxifen. There are also studies of aromatase inhibitors, such as Letrozole, Anastrazole and Exemestane, and COX-2 inhibitors as alternatives to Tamoxifen in preventing breast cancer in postmenopausal carriers of BRCA mutations.
Oral contraceptive use may be helpful, although the research is not as clear cut. For example, oral contraceptive use for 5 or more years is associated with a 50%-60% decreased risk of ovarian cancer in BRCA1/2 carriers but an increased risk of breast cancer among BRCA1 mutation carriers.
Prophylactic (preventive) surgery includes a double mastectomy (removal of the breasts with or without reconstruction), salpingo-oophorectomy (removal of the fallopian tubes and ovaries), and hysterectomy (removal of the uterus).
Prophylatic mastectomy reduces the risk of breast cancer by 90%.
An oophorectomy reduces the risk of breast cancer among BRCA1 and BRCA2 mutation carriers by 53% and the risk of ovarian cancer by 96%. Note that the risk reduction was primarily for premenopausal women, when the ovaries are still producing estrogen.
Oophorectomies are recommended for BRCA carriers when they no longer want any more children.
Prophylactic mastectomy combined with prophylactic oophorectomy reduces the risk of breast cancer by 95%.
Surgery is not able to remove all of the tissue, so there is always a small residual risk of cancer.
In a prospective study of BRCA1 and BRCA2 mutation carriers, 96% of women choosing prophylactic bilateral salpingo-oophorectomy were cancer-free at five years, compared with 69% for carriers choosing intensive surveillance. (Note that 3% of the women choosing surgery were diagnosed with stage I ovarian cancer at the time of surgery.)
Because of the higher risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers, a double mastectomy is often recommended for breast cancer patients who are BRCA carriers.
Surgery, however, also carries some risks. Typically there is a 3% to 5% risk (infection, bleeding, and anesthesia). Thus a carrier who pursues prophylactic surgery is trading a small immediate risk for a large reduction in long-term risk of cancer.
Prophylactic oophorectomy can be performed laparascopically as an outpatient procedure. This reduces the healing time.
Other consequences of surgery include quality of life issues, such as the possibility of pain after surgery and hot flashes after oophorectomy due to surgical menopause.
Hormone replacement therapy does not seem to increase the risk of breast cancer after oophorectomy, but this research is still preliminary. The cancer risk associated with hormone replacement therapy may be dose-dependent, meaning that a low dose estrogen regimen may be safer.
Surgeons are unlikely to adequately discuss all the quality of life issues, which include:
There are other steps carriers can take to reduce their risk of cancer. These include:
The information contained on this web page is for informational purposes only and does not render medical or professional advice. The information on this web page should not be used for diagnosing or treating any medical condition. You are strongly advised to seek professional care from a licensed health care provider. Do not disregard professional medical advice or delay seeking professional medical advice because of anything you may have read on this web page. No warranty is made about the accuracy of the information provided on this web page.
Copyright © 2004 by Mark Kantrowitz. All rights reserved.
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