Helping you assess risk

Abdominal aneurysm

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An abdominal aneurysm usually results from a mix of genetic and environmental causes. Family and case-control studies indicate that about 72 percent of your patient's potential risk is caused by genetic factors.

Men are four times more likely than women to develop this type of aneurysm, with men who have a history of smoking and those over 65 at the highest risk. For younger individuals, having smoked and having a family history increase risk.

Your patient's genetic risk, in the context of his or her family history and other risk factors, can signal whether your patient would benefit from screening for an aneurysm.

Note that the data from the genome study indicate that the genetic variant leads to increased susceptibility for developing an aneurysm, rather than an increased risk of rapid progression or rupture.

Alzheimer's disease

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The Navigenics Health Compass genetic test addresses late-onset disease, not early onset. There are some early and promising things that can be done for Alzheimer's, which we describe to our members on our website. We tell our members that they may be at greater risk than we have reported and should consult a Genetic Counselor if any of their relatives have been diagnosed with Alzheimer's before age 60.

Atrial fibrillation

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In view of an increased tendency to atrial fibrillation, it may be worthwhile to readdress with your patient any symptoms not previously categorized: palpitations, syncope, etc. Reviewing avoidance of precipitating factors such as stimulants and decongestants also may be prudent.

Brain aneurysm

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In view of an increased tendency to brain aneurysm, it may be worthwhile readdressing with your patient any symptoms not previously categorized, such as severe or recurrent headaches or other neurological symptoms, even if they come and go. Viewing these in light of a possible underlying brain aneurysm may be prudent.

Breast cancer

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Our panel does not cover certain important monogenic breast cancers such as Hereditary Breast and Ovarian Syndrome (HBOC), BRCA mutations or Cowden syndrome (PTEN). We tell our members that they may be at greater risk than we have reported and should consult a Genetic Counselor if they answer "yes" to any of these questions:

• Have you or anyone in your family had breast cancer before age 50, cancer in both breasts at any age or ovarian cancer at any age?
• Have two or more close relatives on the same side of your family (maternal or paternal) had breast or ovarian cancer, or has one relative had both?
• Do you have any male relatives with breast cancer?
• Do you have Ashkenazi (Eastern European) Jewish ancestry and at least one family member with breast or ovarian cancer at any age?
• Do you have any relatives with an identified genetic mutation that increases their risk for cancer?

Celiac disease

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Symptoms, if any, may be subtle and mimic irritable colon, etc. Perhaps readdress complaints previously passed over. If the individual's diet is low in gluten, confirmatory tests such as gliadin antibody, endomysial antibody and anti tissue transglutaminase may be negative; so if appropriate a gastroenterologist referral might be considered.

Colon cancer

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Pending evaluation and a detailed family history, it may be appropriate to consider early colon screening. Also note, our panel does not cover certain important monogenic familial colon cancer syndromes such as HNPCC or FAP. We tell our members that they may be at greater risk than we have reported and should consult a Genetic Counselor if they answer "yes" to any of these questions:

• Have you or anyone in your family had colon cancer before the age of 50, or multiple colon polyps?
• Have two or more close relatives on the same side of your family (maternal or paternal) had colon, uterine or ovarian cancer, or has one relative had more than one of these cancers?
• Do you have Ashkenazi (Eastern European) Jewish ancestry and at least one family member with colon cancer at any age?
• Do you have any relatives with an identified genetic mutation that increases their risk for cancer?

Crohn's disease

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Symptoms if any, may be subtle and mimic irritable colon, etc. Perhaps readdress complaints previously passed over.

Deep vein thrombosis

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We test for four SNPs that relate to deep vein thrombosis (DVT). One is associated with Factor V Leiden, one with the prothrombin G20210A mutation (in Factor II), one with the SERPINC1 gene (which encodes antithrombin) and one located in the CYP4V2 gene. Even if your patient is average or below average on our genetic screen for DVT, it is still possible that he or she could be at increased risk based on personal and family history or other relevant risk factors. For instance, having elevated levels of homocysteine in the blood (which can be acquired or inherited) also raises risk for DVT. The Navigenics test does not replace doing the actual protein assays for suspected thrombophilia (Protein C, Protein S and antithrombin deficiencies), but may assist in determining whether such testing is warranted.

Even with no increased risk of DVT based on the Navigenics panel, if your patient has a personal or family history of DVT, especially in someone under age 50; if the same relative had more than one clot; or if there is a family history of recurrent pregnancy loss (e.g. the same person has had more than three pregnancy losses), there may be an underlying genetic cause. If so, additional testing may be appropriate. And if the Navigenics test is shows increased risk it is still appropriate to get confirmatory Factor V Leiden and prothrombin G20210A mutation assays in another clinical laboratory.

Diabetes, type 2

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A baseline Hemoglobin A1c may be appropriate for future reference.

Glaucoma

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Our panel screens for genetic markers that increase the risk for exfoliation glaucoma. Consider obtaining a baseline eye exam with visual fields.

Graves' disease

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You might be attuned to -- and make your patient aware of -- unusual presentations such as diarrhea, fatigue, muscle weakness, etc.

Heart attack

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Consider readdressing borderline lipids.

Hemochromatosis

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We test for several genetic variants in the HFE gene, each conferring different degrees of risk for developing iron overload. At any given time people at genetic risk for hemochromatosis can still have normal iron levels (transferrin saturation and serum ferritin) due to their age, sex, and environmental factors. Consideration should be given to confirming a positive Navigenics screen for hemochromatosis with a standard HFE gene test in a clinical laboratory.

Lactose intolerance

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Lactose intolerance is very common among people of Asian and African descent. However, some Asians and Africans may have two copies of the risk marker that Navigenics tests for, and still be able to tolerate lactose. This is because lactase production may also be regulated at other loci. These loci are not well understood by scientists, and so they are not included in Navigenics’ service. In a patient with symptoms and a positive genetic risk you may want to confirm the diagnosis of lactose intolerance with a lactose tolerance test or hydrogen breath test. Also, remember that other conditions such as celiac disease can result in a secondary form of lactose intolerance.

Lung cancer

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The available data indicate that these results apply primarily to current and former smokers. It's difficult to evaluate non-smokers as they are affected so infrequently. In the study our test relies on most heavily, the researchers found no association between the genetic variant and lung cancer in non-smokers, though the number of non-smokers was small. Another study, however, did show a modest association in non-smokers. An even more recent study provided convincing evidence that the gene variant we test for actually predisposes to nicotine addiction, which in turn raises risk for lung cancer.

This genetic variant was not found to predispose to any subtype of lung cancer in particular. One study found the association in populations of non-small cell lung cancer cases only, another in subgroup analyses of small cell, squamous cell, and adenocarcinomas and a third in a combination of various lung cancer subtypes.

Lupus

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Your patient may have no symptoms, mild symptoms, or symptoms not initially thought to be significantly related to any specific entity. Consider readdressing any complaints that might be related to lupus in view of a possible increased tendency.

Macular degeneration

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A baseline eye exam may be appropriate. Also, instructing your patient in the use of the Amsler Grid to detect degeneration early should be considered.

Melanoma

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When seeing patients who have an increased genetic risk for melanoma, you may want to reexamine their skin or have them see a dermatologist for a skin check. Remember that a melanoma may occur in a dark-complected individual, may be amelanotic and may occur in areas that aren't exposed to the sun.

Also note: Navigenics tests for common markers associated with melanoma. We do not screen for rare mutations in genes such as CDKN2A (also known as p16) or CDK4, which are associated with rare hereditary melanoma syndromes. If you have patients who answer “yes” to any of the questions below, they should be referred to a Genetic Counselor or dermatologist and considered for additional genetic testing.

• Have you or anyone in your family had melanoma (especially two or more cases in the same person)?
• Do you have a personal or family history of melanoma and pancreatic cancer — either both diagnoses occurring in the same family member or in two different relatives?
• Does anyone in your family have a known mutation in a gene associated with hereditary melanoma?
• Have you been diagnosed with multiple atypical or dysplastic nevi?

Multiple sclerosis

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Consider neurological referral for even subtle symptoms, because early treatment might make a difference.

Obesity

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Even if your patient is not obese, and there is no strong family history of such, it may not be unreasonable to remind your patient that caloric needs decrease with age, and the prevalence of obesity increases with age.

Osteoarthritis

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Your patient may have no symptoms, but it may still be reasonable to encourage appropriate lifestyle changes like weight reduction, being careful about repeated joint trauma, etc.

Prostate cancer

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For men at increased genetic risk, consider doing a baseline PSA and digital rectal exam earlier than usual, even if family history is not striking.

Psoriasis

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While classical patches of psoriasis are fairly obvious, consider checking your patient periodically for lesions in less common places, such as the intergluteal region, that may present differently. Also be alert to nail changes and arthritic symptoms that may suggest psoriatic arthritis, which has a better prognosis if treated early.

Restless legs syndrome

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This syndrome appears to be associated with a number of common genetic variants, each having a small effect on its own but a greater impact in combination.

Rheumatoid arthritis

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Consider reassessing even mild joint complaints or questioning your patient about extra-articular rheumatoid symptoms. A baseline sedimentation rate may be helpful in the future.

Sarcoidosis

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Over 60 percent of the risk for sarcoidosis is genetic, probably with an environmental trigger. As a "great masquerader," sarcoidosis needs to be considered in the differential diagnosis of pulmonary, dermatologic, and arthritic complaints especially with lymphadenopathy. A person’s increased genetic predisposition for sarcoidosis can serve as a clue to understanding varied and vague complaints. Confirmatory tests may be appropriate.

Stomach cancer, diffuse

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Navigenics tests for common genetic markers associated with diffuse stomach cancer. Much less common are single-gene mutations that carry a much greater likelihood of diffuse stomach cancer. Navigenics does not test for these rare single-gene mutations. If your patient answers "yes" to any of the questions below, you should have the person consult a Genetic Counselor.

• Have two or more close relatives in your family had diffuse stomach cancer, with at least one person diagnosed before age 50?
• Have three or more close relatives been diagnosed with diffuse stomach cancer at any age?
• Has a close relative been diagnosed with diffuse stomach cancer before age 40?
• Has a close relative been diagnosed with both diffuse stomach cancer and lobular breast cancer?
• Has a close relative been diagnosed with diffuse stomach cancer and a different family member with either lobular breast cancer or signet ring colon cancer?

Although the association between H. pylori and the intestinal form of stomach cancer is better understood, there may also be an association between H. pylori and diffuse stomach cancer. You may want to consider having your patient tested for H. pylori.