Cancer Predisposition In Children 

What Is Cancer Predisposition In Children?

[dropcap]C[/dropcap]ancer predisposition in children signifies a higher than normal risk of developing cancer. Cancer is the uncontrolled division of abnormal cells in the body.

Among the 12 major types of childhood cancers, leukemias (blood cell cancers) and cancers of the brain and central nervous system account for more than half of the new cases. About one-third of childhood cancers are leukemias.

The most common type of leukemia in children is acute lymphoblastic leukemia. The most common solid tumors are brain tumors (e.g., gliomas and medulloblastomas), with other solid tumors (e.g., neuroblastomas, Wilms tumors, and sarcomas such as rhabdomyosarcoma and osteosarcoma) being less common according to the National Cancer Institute.

On average, 1 to 2 children develop the disease each year for every 10,000 children in the United States.

What Is Cancer Predisposition In Children In Celiac Disease and/or Gluten Sensitivity?

• Relationship between cancer predisposition in children and celiac disease. Cancer predisposition in children is a serious complication of untreated celiac disease. It is characterized by an increased number of chromosome abberations in peripheral blood lymphocytes.¹ Peripheral blood lymphocytes are a type of white blood cell that circulates in blood.

Q: What are chromosome abberations?

A: Chromosome abberations are unwanted changes that can affect the structure or function of lymphocytes and, ultimately, can result in their death. Chromosome damage itself is involved in the pathway to cancer.²

• Relationship between cancer predisposition in children and folate metabolism. The results of the European Collaborative Project involving 22,000 subjects confirm that a high level of chromosomal aberrations is associated with an increased risk of cancer and indicate that this association does not depend on the time between chromosomal aberrations analysis and cancer detection, that is, it is obviously not explained by undetected cancer. Of extreme interest is the finding that folate metabolism affects the level of chromosomal aberrations.³

• Relationship between cancer predisposition in children and zinc deficiency. A study by Milne et al. investigating whether nutritional factors are associated with telomere length (TL) in healthy children found  an inverse relationship with zinc (the lower the zinc level, the shorter the TL). Telomeres are long hexamer (TTAGGG) repeats at the ends of chromosomes, and contribute to maintenance of chromosomal stability. Telomere shortening has been linked to cancers and other chronic diseases in adults, although evidence for causal associations is limited.⁴

How Prevalent Is Cancer Predisposition In Children In Celiac Disease and/or Gluten Sensitivity?

Prevalence is not established but is documented in case reports and studies as an association with celiac disease.⁵

What Are The Symptoms Of Cancer Predisposition In Children?

• Cancer predisposition in children is asymptomatic (without symptoms).
• It is found by laboratory examination of blood.

How Does Cancer Predisposition In Children Develop In Celiac Disease and/or Gluten Sensitivity?

• Predisposition to cancer results from an unclear etiology.
• The study below by Kolacek et al. demonstrated that the frequency of chromosome abberations in peripheral blood lymphocytes decreased significantly on a gluten free diet. The researchers conclude that genomic instability is a secondary phenomenon, possibly caused by intestinal inflammation. Frequency of chromosome abberations at follow-up remained unchanged in children who were not diet adherant.⁶
• Defective folate metabolism affects the level of chromosomal aberrations and might collectively contribute to the cancer predictivity of chromosome abberations.⁷
• The mean plasma retinol (vitamin A) and alpha-tocopherol (vitamin E) concentration in the samples of untreated celiacs was significantly lower than in treated celiacs. It is possible that celiac disease patients may be helped by dietary supplementation rich in vitamin A (and E) to minimize the risk of cancer development.⁸
• Shortened telomere length (TL) in healthy children was inversely related with zinc (the lower the zinc level, the shorter the TL).⁴

Does Cancer Predisposition In Children Respond To Gluten-Free Diet?

Yes. Celiac disease-related chromosome abberations respond to a gluten free diet. Frequency of chromosome abberations at follow-up remained unchanged in children who were not diet adherant.¹

It is possible that celiac disease patients may be helped by dietary supplementation rich in vitamin A (and E) to minimize the risk of cancer development.⁹

Correction of zinc deficiency may improve telomere shortening, an abberation of chromosomes.

6 Steps To Improve Cancer Predisposition In Children In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment of celiac disease and non-celiac gluten sensitivity. This condition responds to the complete elimination of gluten, which is the required treatment that improves both cancer risk and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Treatment for predisposition to cancer:

1. Remove gluten from the diet at once.
2. Change the diet to remove inflammatory foods (see below) and
3. Increase anti-inflammatory foods, especially a variety of plant foods that have been shown to kill cancer cells especcially these:

• Turmeric spice.  Many studies show that tumeric extracts inhibit the growth of numerous cancers including leukemia, lymphoma, breast, nasopharyngeal, lung, cervical, and colon cancer cells, along with one noncancer human fibroblast cell line. These extracts exhibited potent killing effects against cancer cells.
• Pineapple fruit. Use fresh, canned or juice of pineapples. Heating does not harm the cancer killing effects of bromelein which is the substance doing the killing.

Recovery from intestinal damage due to gluten. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.¹⁰
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.¹¹
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.¹¹
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.¹¹.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.¹¹
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.¹¹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹¹[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain medications cause deficiencies of  vitamin A, Vitamin E, and folic acid that appear to promote cancer predisposition in childhood.

Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

 This is not a complete listing.

ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete Folic Acid, Vitamin A.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Folic Acid, Vitamin A
• Alka Seltzer®, Baking Soda deplete Folic Acid.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Folic Acid.
• NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.
• Aspirin and Salicylates deplete Folic acid.

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Folic Acid. [/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Vitamin A as prescribed following blood test for status.
• Vitamin E as prescribed following blood test for status.
• Folic acid as prescribed following blood test for status.
• Zinc gluconate as prescribed following blood test for status.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Two to four glasses of water depending on age of child are recommended per day unless there is a contraindication such as kidney or heart disease.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Turmeric also fights cancer!
• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Cancer Predisposition In Children In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Plasma micronutrient levels and telomere length in children.” This study investigating whether nutritional factors are associated with telomere length (TL) in healthy children found  an inverse relationship with zinc (the lower the zinc level, the shorter the TL). The reason for the inverse relationship of TL with zinc is unknown but could be the result of an increase in telomere sequence deletions caused by labile zinc induction of oxidative stress.

Telomeres are long hexamer (TTAGGG) repeats at the ends of chromosomes, and contribute to maintenance of chromosomal stability. Telomere shortening has been linked to cancers and other chronic diseases in adults, although evidence for causal associations is limited.

This cross-sectional study measured nutritional factors and TL in 437 children between 2009 and 2011. Healthy children ages 3, 6, and 9 y provided blood samples, and their parents completed a food frequency questionnaire and a telephone interview about relevant environmental exposures. TL and blood micronutrient levels were measured, and genotyping at 10 loci was undertaken. Associations between the icronutrients and other variables were assessed using linear regression.

After adjustment for age, sex, parental education, and month of blood collection, TL was inversely associated with plasma zinc, and shorter in children with the homozygous mutant genotype of the RFC G80A (rs1051266) polymorphism.⁴

“Oxidatively damaged DNA/oxidative stress in children with celiac disease.” This study seeking to characterize oxidative stress/oxidative DNA damage as a marker of cancer risk in children with celiac disease found that although diet can be partially responsible for oxidative stress/oxidatively damaged DNA in celiac patients, there is a factor independent of diet.

Two kinds of oxidatively damaged DNA biomarkers, namely, urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively damaged DNA in the leukocytes, as well as the level of antioxidant vitamins were analyzed using high-performance liquid chromatography (HPLC) and HPLC/gas chromatography with isotope dilution mass detection methods. These parameters were determined in three groups: (a) children with untreated celiac disease, (b) patients with celiac disease on a strict gluten-free diet, and (c) healthy children.

Results show the mean level of 8-oxodG in DNA isolated from the leukocytes and in the urine samples of the two groups of celiacs was significantly higher than in controls, irrespective of diet. There was no statistically significant difference in these parameters between treated and untreated celiacs. The mean plasma retinol and alpha-tocopherol concentration in the samples of untreated celiacs was significantly lower than in treated celiacs. It is possible that celiac disease patients may be helped by dietary supplementation rich in vitamin A (and E) to minimize the risk of cancer development.¹²

“Oxidatively damaged DNA/oxidative stress in children with celiac disease.” This study seeking to characterize oxidative stress/oxidative DNA damage as a marker of cancer risk in children with celiac disease found that although diet can be partially responsible for oxidative stress/oxidatively damaged DNA in celiac patients, there is a factor independent of diet.

Two kinds of oxidatively damaged DNA biomarkers, namely, urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively damaged DNA in the leukocytes, as well as the level of antioxidant vitamins were analyzed using high-performance liquid chromatography (HPLC) and HPLC/gas chromatography with isotope dilution mass detection methods. These parameters were determined in three groups: (a) children with untreated celiac disease, (b) patients with celiac disease on a strict gluten-free diet, and (c) healthy children.

Results show the mean level of 8-oxodG in DNA isolated from the leukocytes and in the urine samples of the two groups of celiacs was significantly higher than in controls, irrespective of diet. There was no statistically significant difference in these parameters between treated and untreated celiacs. The mean plasma retinol and alpha-tocopherol concentration in the samples of untreated celiacs was significantly lower than in treated celiacs. It is possible that celiac disease patients may be helped by dietary supplementation rich in vitamin A (and E) to minimize the risk of cancer development.¹²

“Chromosomal aberrations and SCEs as biomarkers of cancer risk.” The results of a European Collaborative Project involving 22,000 subjects confirm that a high level of chromosome abberations is associated with an increased risk of cancer and indicate that this association does not depend on the time between chromosomal aberrations analysis and cancer detection, i.e., is obviously not explained by undetected cancer. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of chromosomal aberrations and might collectively contribute to the cancer predictivity of chromosome abberations. Other factors that may influence the association between chromosomal aberrations and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species.¹³

“Gluten-free diet has a beneficial effect on chromosome instability in lymphocytes of children with coeliac disease.” This study investigating a group of children with celiac disease in whom the initial frequency of chromosome abberations at diagnosis was known and to measure the same variable after a minimum of 2 years on a gluten free diet demonstrated that the frequency of chromosome abberations in peripheral blood lymphocytes decreased significantly on a glutenfFree diet. The study concluded that genomic instability is a secondary phenomenon, possibly caused by intestinal inflammation. Frequency of chromosome abberations at follow-up remained unchanged in children who were not diet adherant.¹

Sources:

1. Kolacek S, Jadresin O, Petkovic I, Misak Z, Sonicki Z, Booth IW. Gluten-free diet has a beneficial effect on chromosome Instability in Lymphocytes of children with coeliac disease. Journal of Pediatric Gastroenterology and Nutrition. Feb 2004;38(2):177-80. [↩] [↩] [↩]
2. Bonassi S, Hagmar L, Strömberg U, Montagud AH, Tinnerberg H, Forni A, Heikkilä P, Wanders S, Wilhardt P, Hansteen IL, Knudsen LE, Norppa H. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health. Cancer Res. 2000 Mar 15;60(6):1619-25. [↩]
3. Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, Boffetta P, Lindholm C, Gundy S, Lazutka J, Cebulska-Wasilewska A, Fabiánová E,Srám RJ, Knudsen LE, Barale R, Fucic A. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res. 2006 Aug 30;600(1-2):37-45. [↩]
4. Milne E, O’Callaghan N, Ramankutty P, de Klerk NH, Greenop KR, Armstrong BK, Miller M, Fenech M. Plasma micronutrient levels and telomere length in children. Nutrition. 2015 Feb;31(2):331-6. [↩] [↩] [↩]
5. Kolacek S, Jadresin O, Petkovic I, Misak Z, Sonicki Z, Booth IW. Gluten-free diet has a beneficial effect on chromosome Instability in lymphocytes of children with coeliac disease. Journal of Pediatric Gastroenterology and Nutrition. Feb 2004;38(2):177-80. [↩]
6. Kolacek S, Jadresin O, Petkovic I, Misak Z, Sonicki Z, Booth IW. Gluten-free diet has a beneficial effect on chromosome Instability in lymphocytes of children with coeliac disease. Journal of Pediatric Gastroenterology and Nutrition. Feb 2004;38(2):177-80. [↩]
7. Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, Boffetta P, Lindholm C, Gundy S, Lazutka J, Cebulska-Wasilewska A, Fabiánová E,Srám RJ, Knudsen LE, Barale R, Fucic A. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res. 2006 Aug 30;600(1-2):37-45. Epub 2006 Jul 11. [↩]
8. Szaflarska-Poplawska A1, Siomek A, Czerwionka-Szaflarska M, Gackowski D, Rózalski R, Guz J, Szpila A, Zarakowska E, Olinski R. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1960-5. doi: 10.1158/1055-9965.EPI-10-0295. [↩]
9. Szaflarska-Poplawska A1, Siomek A, Czerwionka-Szaflarska M, Gackowski D, Rózalski R, Guz J, Szpila A, Zarakowska E, Olinski R. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1960-5. doi: 10.1158/1055-9965.EPI-10-0295. [↩]
10. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
11. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
12. Szaflarska-Poplawska A1, Siomek A, Czerwionka-Szaflarska M, Gackowski D, Rózalski R, Guz J, Szpila A, Zarakowska E, Olinski R. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1960-5. doi: 10.1158/1055-9965.EPI-10-0295. [↩] [↩]
13. Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, Boffetta P, Lindholm C, Gundy S, Lazutka J, Cebulska-Wasilewska A, Fabiánová E,Srám RJ, Knudsen LE, Barale R, Fucic A. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res. 2006 Aug 30;600(1-2):37-45. [↩]