According to a research study by the University of Exeter Medical School in the United Kingdom, men with hemochromatosis, a common genetic disorder due to iron build-up, are ten times more likely to develop liver cancer. 

What is Hemochromatosis?

Hemochromatosis, also called the iron-overload disease, is a condition where too much iron builds up in the body. Usually, the intestines absorb adequate amounts of iron and excrete the rest.

With hemochromatosis, excess iron is absorbed by the intestines, and the body has no way of getting rid of it. As a result, iron gets built up in joints, the pituitary gland, and organs like the liver, heart, and pancreas.

This gradually results in the shutting down of these organs if hemochromatosis is not treated.

Hemochromatosis is more serious in men. Women may be partially protected as they lose some iron during menstruation and childbirth.

Some common symptoms associated with hemochromatosis include:

  1. Joint pain
  2. Weight loss
  3. Fatigue
  4. Low sex drive
  5. Abdominal pain

The HFE Gene

HFE gene is associated with iron homeostasis. A variant (type) of the HFE gene, called the C282Y (the faulty type), is significantly associated with hereditary hemochromatosis.

According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins.

Hemochromatosis and Liver Cancer

With hemochromatosis, the iron build-up is commonly seen in the liver. This enlarges the liver and messes up the liver enzymes. It can result in an increased risk of liver conditions like cirrhosis, fibrosis, and cancer. 

Hepatocellular carcinoma (HCC), a primary form of liver cancer, was the first condition in which hepatic iron overload was shown to predispose to the development of HCC.

According to a study, 8-10% of people with hemochromatosis develop HCC.

The Study

The study was led by the University of Exeter Medical School along with the University of Connecticut, Western University in Ontario, and South Warwickshire NHS Foundation Trust.  

This study focused on men and women with two copies of the faulty HFE gene - C282Y. The data of 2890 people aged 40-70 years were analyzed over a nine-year period.

The following were observed:

  1. 21 out of the 1,294 men with faulty genes developed liver cancer
  2. 14 out of these 21 men died of liver cancer
  3. 10 out of these 21 men were not diagnosed with hemochromatosis by the time they developed liver cancer
  4. **More than 7% of the men** with two faulty genes develop liver cancer by 75 years of age
  5. No increase in liver cancer risk was found in women with the faulty genes

The study insists on the importance of early diagnosis of hemochromatosis in order to avoid health complications and even death.

The NHS advises that “it is important to talk to your GP if you have a parent or sibling with hemochromatosis, even if you don’t have symptoms yourself” to identify your risk. 

The lack of impact on women from the faulty HFE gene variant may suggest that periodic blood donations might play a protective role.

Summary

  1. Hemochromatosis is a condition where your body absorbs too much iron resulting in its build-up in joints and organs. It leads to complications like low sex drive, fatigue, and abdominal pain.
  2. When iron builds up in the liver, it can alter the size of the liver and disturb the liver enzymes. Both these factors contribute to the increased susceptibility to liver diseases like fibrosis, cirrhosis, and cancer.
  3. The HFE gene is associated with the regulation of iron levels in the body. The faulty type of the HFE gene called C282Y increases your risk for hemochromatosis. 
  4. A study by the University of Exeter Medical School revealed that men with two copies of the faulty gene are at an increased risk of developing liver cancer. According to the study, by the age of 75, more than 7% of these men had developed liver cancer. No association was found in women with the faulty genes and liver cancer risk.
  5. Genetic testing, which analyzes your HFE gene type, is a key way to prevent and manage hemochromatosis. The NHS advises people who have a sibling or a close family member with hemochromatosis to talk to their healthcare provider for suitable tests.

Reference:

  1. https://www.sciencecodex.com/liver-cancer-ten-times-more-likely-men-common-genetic-disorder-haemochromatosis-661896
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668053/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995380/

The Tumor Necrosis Factor Alpha (TNFA) gene is associated with the synthesis of TNFA, a pro-inflammatory cytokine that regulates immune responses such as inflammation. Specific alleles of this gene are known to either increase or decrease the levels of TNFA. People with the A variant of the gene are found to synthesize more TNFA which affects fatigue, inflammatory response, diabetes and cardiovascular risk and response to training.

Association with speed of recovery: 

People with the A variant require longer recovery times compared to people with the G variant. A study which was part of the HERITAGE study  measured CRP before and after an endurance training programme lasting 20 weeks. The baseline CRP levels were higher among people with the A variant when compared to people with the G Variant. After the training programme, there was a higher increase in CRP among people with the A variant than among people with the G variant. This shows that people with the A variant required longer recovery periods in between intense exercise. A study conducted to identify the association between physical exercise and anti-inflammatory response found that polymorphisms in TNFA gene was associated with the levels of serum C reactive protein after moderate to vigorous physical activity. People with the G variant had a greater decrease in C reactive protein upon physical activity than people with the A variant.

Does your 23andme, Ancestry DNA, FTDNA raw data have TNFA gene variant information?

CHIP VersionTNFA SNPs
23andMe (Use your 23andme raw data to know your TNFA Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your TNFA Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your TNFA Variant)
OmniExpress microarray chipPresent

Association with fatigue

In a study conducted on the influence of TNFA gene polymorphisms on fatigue, people with the A variant of the gene were associated with increased sleep disturbance and fatigue than people with the G variant. In another study conducted on elderly women, people with the G variant had a better physical performance independent of their exercise modality.

Association with Cholesterol levels In a study aimed at understanding the metabolic response of people on a high protein/low carbohydrate diet showed that people with the GG genotype had a greater reduction in total cholesterol, triglycerides and LDL cholesterol.

Association with Diabetes/ Impaired Glucose tolerance: 

In a study conducted as a part of the Finnish Diabetes Prevention Study, the presence of the A variant was shown to be a predictor for the conversion from Impaired Glucose Tolerance (IGT) to type 2 Diabetes. Another study showed that the presence of the A variant of the gene was associated with an increased risk for diabetes and higher glucose levels in the body.

Association with Bone Mineral Density:

In a study conducted on postmenopausal women, people with the A variant were associated with increased risk for osteoporosis. Higher levels of cytokines lead to an increase in bone breakdown.

Association with Cardiovascular Diseases

People with the A variant were shown to have an increased risk for acute myocardial infarction.

Genotype rs1800629PhenotypeRecommendation
AA[Limitation] More likely to have higher TNFA level [Limitation] More likely to have higher levels of inflammation after intense exercise [Limitation] More likely to require longer period of recovery [Limitation] More likely to have higher level of fatigue [Limitation] More likely to have higher risk for Diabetes [Limitation] More likely to have higher risk for Myocardial Infarction [Limitation] More likely to have lower reduction in triglyceride, cholesterol levels on a high protein/ low carbohydrate dietLikely to have lower reduction in inflammation upon exercising than G variants. Increased risk for fatigue post exercises requires optimum periods of rest between repetitions Include 3g of  Omega 3 fatty acids in the diet which is found to lower the levels of inflammation
AGModerate level of C reactive protein and more likely to have moderate level of risk for diabetesLikely to have lower reduction in inflammation upon exercising than G variants. Increased risk for fatigue post exercises requires optimum periods of rest between repetitions Include 3g of  Omega 3 fatty acids in the diet which is found to lower the levels of inflammation
GG[Advantage] More likely to have normal level of TNFA [Advantage] More likely to have lower levels of inflammation after intense exercise [Advantage] More likely to require shorter period of recovery [Advantage] More likely to have lower level of fatigue [Advantage] More likely to have lower risk for Diabetes [Advantage] More likely to have lower risk for Myocardial Infarction [Advantage] More likely to have higher reduction in triglyceride, cholesterol levels on a high protein/ low carbohydrate dietLikely to have higher reduction in inflammation upon exercising Include Omega 3 fatty acids in the diet

References:

  1. https://www.ncbi.nlm.nih.gov/pubmed/27706628
  2. https://www.ncbi.nlm.nih.gov/pubmed/27513494
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983298/
  4. https://www.ncbi.nlm.nih.gov/pubmed/23430759/
  5. https://www.ncbi.nlm.nih.gov/pubmed/20361391
  6. https://www.ncbi.nlm.nih.gov/pubmed/12829659
  7. https://www.ncbi.nlm.nih.gov/pubmed/26914399

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

The MCT1 gene is associated with the synthesis of MCT1, a molecule that transports lactic acid across the muscle cell membrane. Specific alleles of this gene are known to either increase or decrease the risk for fatigue and muscle injury after intense exercises. People with the T variant of the gene are associated with lower transport of lactic acid due to lower levels of MCT1, implying that they could experience earlier fatigue onset on exercising.

Does your 23andme, Ancestry DNA, FTDNA raw data have MCT1 gene variant information?

CHIP VersionMCT1 SNPs
23andMe (Use your 23andme raw data to know your MCT1 Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your MCT1 Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your MCT1 Variant)
OmniExpress microarray chipPresent

Association with Running:

A study conducted on sprint/power athletes showed that those with the TT genotype of MCT1 were associated with power athletes when compared to people with the A variant. Conversely, in a study conducted on rowers, the AA genotype was associated with greater frequency among endurance athletes.

Association with Muscle Injury:

People with the AA genotype are at a higher risk of muscle injury while the T variant of the gene may have a protective effect due to lowered transport of lactic acid into muscles for oxidation.

GenotypePhenotypeRecommendation
TT[Limitation] Lower lactate threshold, hence early fatigue onset [Advantage] More likely to have lower risk of muscle injury [Advantage] Better sprint running performanceHigher risk of fatigue- Mild to moderate intensity exercises will aid in lowering risk of fatigue Better sprint running performance Lower risk of muscle injury- Strength training results in low lactate accumulation for people with T variant. Increasing the intake of magnesium rich foods in the diet like kidney beans, navy beans and pinto beans lower accumulation of lactic acid.
ATModerate risk of fatigueBetter at endurance activities, such as long distance running, playing tennis, basketball, dancing and aerobics. Increased risk for muscle injuries- Carrying out mild to moderate intensity exercises will lower risk of injuries. Strength training should be carried out with lower weight and more repetitions
AA[Advantage] Higher lactate threshold, hence later fatigue onset [Limitation] More likely to have higher risk of muscle injury [Advantage] Better endurance running performanceBetter at endurance activities, such as long distance running, playing tennis, basketball, dancing and aerobics. Increased risk for muscle injuries- Carrying out mild to moderate intensity exercises will lower risk of injuries. Strength training should be carried out with lower weight and more repetitions

References:

  1. Sawczuk M, Banting LK, Cięszczyk P, Maciejewska-Karłowska A, Zarębska A, Leońska-Duniec A, Jastrzębski Z, Bishop DJ, Eynon N. “MCT1 A1470T: a novel polymorphism for sprint performance?”; J Sci Med Sport. 2015 Jan
  2. Myosotis Massidda, Nir Eynon, Valeria Bachis, Laura Corrias, Claudia Culigioni, Francesco Piras, Paolo Cugia, Marco Scorcu and Carla M. Calò; “Influence of the MCT1 rs1049434 on Indirect Muscle Disorders/Injuries in Elite Football Players”; Sports Medicine – 2015
  3. Fedotovskaya ON1, Mustafina LJ, Popov DV, Vinogradova OL, Ahmetov II.; “A common polymorphism of the MCT1 gene and athletic performance.”; Int J Sports Physiol Perform. 2014 Jan
  4. https://www.omicsgroup.org/journals/association-between-ventilatory-thresholds-related-to-aerobic-fitness-and-mct1-a1470t-polymorphism-2473-6449-1000105.php?aid=69866&view=mobile
  5. http://www.sciencedirect.com/science/article/pii/S1440244012000370
  6. https://fitnessgenes.com/how-it-works/genes-we-analyze/mct1/
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