Are you more likely to get cancer if you have Gilbert’s Syndrome?

woman looking into a microscope while seated at a desk

Please note that I am not medically qualified. If you have concerns about your health you should seek advice from a medically qualified professional. The information provided is based on publicly available sources, and is no substitute for personal healthcare. It is important to understand that there is much more research needed into Gilbert’s Syndrome, and no single study is definitive. 

Summary

  • If you have Gilbert’s Syndrome your UGT1A1 gene and enzyme are affected. It is not proven, but some think that this may also reduce your ability to deal with cancer causing toxins and hormones as well as drugs which treat cancer.
  • Depending on your heritage you may have different variations of the Gilbert’s Syndrome gene.
  • The gene variant most commonly causing Gilbert’s Syndrome has been linked to colorectal and lung cancer, and oestrogen which may affect breast cancer. 
  • However, there are no proven direct links to Gilbert’s Syndrome and getting cancer
  • This gene is one small part of a very complicated puzzle. There are many other factors in the development of cancer. These include your environment, diet, health, gender, age, background, and many other genes. 
  • It would take a great deal more research to prove a clear risk. 
  • What can you do to ensure you reduce your cancer risk? A healthy lifestyle is the best way to reduce your risk of cancer. A diet that focuses on plants, regular moderate exercise such as walking in nature, a resilient mindset, good sleep and social networks all help reduce your risk.

Read on to find out more…

The gene that is thought to increase risk of cancer. 

Gilbert’s Syndrome is caused by a variation in your genes. The gene usually responsible is the UGT1A1*28 variant. This means you have 30% to 40%  less of an enzyme that processes bilirubin and certain toxins in your body. There are other variants that have been found to cause Gilbert’s Syndrome, such as UGT1A1*1, *6 and *36. These other variants are often linked to your heritage.

You can read more about the differences in some of the papers below

UGT1A1 is the only enzyme that can glucuronidate bilirubin.

When it comes to the relationship between the UGT1A1 enzyme, carcinogens (cancer-causing substances), and cancer risk, research has mainly looked at the enzyme’s role in metabolising certain drugs and toxins. Some carcinogens and toxins are processed by UGT1A1 through ‘glucuronidation‘, which helps your body get rid of them.

The role of UGT1A1 and its genetic variants to specific types of cancer can vary. Some studies have explored the link between UGT1A1*28 and certain types of cancer, such as colorectal cancer and lung cancer. The thinking behind these studies is that reduced UGT1A1 activity could affect the body’s ability to metabolise and eliminate certain carcinogens. It is thought that this potentially increases cancer risk. However, the results have been mixed and not always consistent across different populations and studies.

Digging deeper into the science

A number of case-control studies have investigated the thinking that the gene could be linked to cancer. These studies identified lots of different UGT variations in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers. These include bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT variations may be cancer causing, or be linked to other UGT genes or neighbouring genes. https://pubmed.ncbi.nlm.nih.gov/26828111/

As recently reviewed [37], case-control studies have shown that a large number of genetic polymorphisms of UGT genes are associated with cancer development and progression. This is believed to be related to the critical roles of UGT enzymes in the systemic metabolism and clearance of carcinogens, cancer-modulating molecules, and anticancer drugs.’

https://www.mdpi.com/2072-6694/13/17/4491/htm

Here are some of the studies looking into the link between the gene and cancer.

  • This study looked at the impact on breast cancer https://pubmed.ncbi.nlm.nih.gov/15111762/ ‘When stratified by age, carrying the *28 allele was associated with an increased risk of breast cancer among women aged less than 40 years (odds ratio [OR] = 1.7; 95% CI = 1.0-2.7) but not among women 40 years old and over (OR = 0.8; 0.7-1.1).’
  • Studies suggest that when people with this variant eat food containing cancer-causing chemicals, such as well-done red meat, less of the cancer-causing chemicals from the meat get deactivated [78].
  • A study in 765 people found that having two copies of UGT1A1*28 was associated with higher odds of having lung cancer [79].
  • Similar associations have been found for UGT1A1*28 and breast cancer (240 and 2130 subjects), and colon cancer (168 subjects) [80, 81, 82].

Conclusion

It’s important to note that cancer is a disease influenced by a combination of genetic, environmental, and lifestyle factors. While the UGT1A1 enzyme’s role in metabolising carcinogens is relevant, it’s only one piece of the complex puzzle of cancer development. If you have concerns about your cancer risk you must consult with a healthcare professional. They can provide personalised guidance based on your medical history, genetic profile, and other risk factors.

How to reduce your cancer risk

You can’t reliably prevent yourself from getting cancer. But you can certainly reduce your risk considerably. Here are the top things you can do that are also great for you if you have Gilbert’s Syndrome = a win win!

If you need a health coach to help you achieve a healthy happy life with Gilbert’s Syndrome you can find out more here.

Liver help – the basics

The liver is the body’s largest solid organ. It responsible for detoxifying many of the potentially harmful substances that can pollute the body.

The liver also plays a critical role in many other body processes including energy production, digestion, and nutrient storage.

What will help my liver?

The cornerstone of any liver-friendly programme is a diet that makes it easier for your liver to work. Lots of fruits and vegetables will help you and your liver work better.

Not only do these foods tend not to tax and stress the liver, they also contain an lots of nutrients such as vitamin C and carotenoids (e.g. beta-carotene) which can support liver function.

Organic produce is best as this is relatively free of potentially toxic herbicides, pesticides and fungicides.

Drinking plenty of water (about one and-a-half to two litres a day) really helps your body and your liver work well.

What won’t help my liver?

Foods that contain artificial additives such as sweeteners, colourings, flavourings and preservatives might cause your liver more problems.

People with Gilbert’s Syndrome often find that drinking alcohol gives them symptoms such as fatigue, brain fog and jaundice. Alcohol is hard for your liver to process and the less you drink the less stressed your liver will be. Watch out for hidden alcohol! You might find some herbal tinctures or food contains alcohol – worth avoiding if you are particularly sensitive.

You might also find fatty food makes you feel sick, and carbohydrates like sugar and white bread or pasta leave you drained and feeling rough. In Gilbert’s Syndrome you need to keep balanced blood sugar levels to help your enzymes work as well as possible (check out ‘What is Gilbert’s Syndrome’ for an explanation), so refined carbs are best avoided.

Pharmacist survey finds ‘Medicines detox’ puts people at risk

A recent article from Net Doctor has food for thought for those of us on long term medication. Please don’t take initiatives with your medication – talk to your Doctor or Pharmacist first! :

Patients are putting themselves at risk of serious harm by believing it is beneficial to occasionally stop taking long-term medicines in order to given their body a ‘detox’, experts have warned.

Research by the National Pharmacy Association (NPA) suggests that one in five people believe a so-called ‘medicines detox’ is beneficial.

However, the NPA warned that this could be seriously harmful for patients with conditions such as diabetes, asthma or depression, as they could lose control of their illness.

The survey also revealed that nearly one in three people believe it is safe to take non-prescription medicines that have been recommended for other people.

And some wrongly assume it is okay for a child to take an adult’s medication, as long as the dosage is reduced.

NPA head of information Leyla Hannbeck said: ‘There is a lot of misunderstanding about how medicines work in your body.

‘It’s important to get the right treatment and the right advice – which you can get from your local pharmacy, often without an appointment.’

Pharmacies provide a wealth of services in addition to dispensing medicines.

These include the disposal of unwanted medicines, promotion of healthy lifestyles and support for self-care.

Pharmacists can also provide personalised advice on medicines, smoking cessation support and guidance on sexual health.ADNFCR-554-ID-800789373-ADNFCR

General anesthesia in a patient with Gilbert’s syndrome.

Having had an operation this year, with a very understanding anesthesiologist, I know that this is an area of poor knowledge in the health service, and that all the advice you as a patient can offer is helpful, and will of course help yourself. We decided that morphine would be avoided and took an approach that would mean using as few drugs as possible. This also meant I would come out of the procedure more alert and able to get going.

There has been some recent research in India which follows the clinical experience I have personally had – namely that the best outcomes are if the drugs used avoid using the enzyme that people with Gilbert’s Syndrome are deficient in:

Source

Department of Anaesthesiology and Critical Care, Tata Main Hospital (TMH), Jamshedpur, India. Nag DS, Sinha N, Samaddar DP, Mahanty PR.

Abstract

Gilbert’s syndrome, caused by relative deficiency of glucuronyl transferase is the commonest cause of congenital hyperbilirubinemia. We report anesthetic management in a case of Gilbert’s syndrome for laparoscopic cholecystectomy under general anesthesia. Avoiding drugs which use this enzyme for its metabolisim or excretion, and minimizing the stress during the perioperative period allows safe conduct of anesthesia for these patients.

Glucuronidation – where Gilbert’s Syndrome works in your liver

Glucuronidation
The UGT enzyme (that people with Gilbert’s Syndrome don’t have so much of) works in one particular part of your liver and is responsible for the part (or pathway) of your liver’s processing called ‘glucuronidation’. Glucuronidation happens when toxins are bound to glucuronic acid which is produced by the liver. Chemicals processed by glucuronidation include common opiate based drugs used in pain relief or during surgery  (Liston, H.; Markowitz, J.; Devane, C. (2001). “Drug glucuronidation in clinical psychopharmacology”. Journal of clinical psychopharmacology). Other things that affect glucuronidation include smoking, obesity, age and gender.

You can find a list of drugs affected here: https://en.wikipedia.org/wiki/Glucuronidation#General_influencing_factors

Some herbal supplements may help glucuronidation (Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. March 2011 Mohamed ME, Frye RF.Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.)The use of herbal supplements has increased steadily over the last decade. Recent surveys show that many people who take herbal supplements also take prescription and nonprescription drugs, increasing the risk for potential herb-drug interactions. In vitro and animal studies indicate that cranberry, gingko biloba, grape seed, green tea, hawthorn, milk thistle, noni, soy, St. John’s wort, and valerian are rich in phytochemicals that can modulate UGT enzymes. However, the IN VIVO consequences of these interactions are not well understood. Only three clinical studies have investigated the effects of herbal supplements on drugs cleared primarily through UGT enzymes. The need for further research to determine the clinical consequences of the described interactions is highlighted.

Essential for Glucuronidation are the nutrients L-glutamine, aspartic acid, iron, magnesium, B3 (niacin) and B6. Thyroid should also be adequate. Cruciferous vegetables (cauliflower, cabbage, cress, bok choy, broccoli and similar green leaf vegetables) are helpful. Glucuronidation efficiency can be improved by calcium-d-glucarate. However, you have to start very gradually with the calcium-d-glucarate, and be very consistent.

You can find out more about glucuronidation here https://youarethehealer.org/health-conditions/optizmize-your-health/detox-biotransformation-pathways/glucuronidation/

Alcohol and Gilbert’s Syndrome

People with Gilbert’s Syndrome can experience unpleasant reactions when they drink alcohol, although it doesn’t bother some people at all. Here is what happens in the body when you drink:

Alcohol is metabolized extremely quickly by the body – absorbed and metabolized before most other nutrients. About 20% is absorbed directly across the walls of an empty stomach and can reach the brain within one minute.

Once alcohol reaches the stomach, it begins to break down with the alcohol dehydrogenase enzyme. This process reduces the amount of alcohol entering the blood by approximately 20%. (Women produce less of this enzyme, which may help explain why women become more intoxicated than men).

About 10% of the alcohol is expelled in the breath and urine.

Alcohol is rapidly absorbed in the upper portion of the small intestine. The alcohol-laden blood then travels to the liver via the veins and capillaries of the digestive tract, which affects nearly every liver cell. The liver cells are the only cells in our body that can produce enough of the enzyme alcohol dehydrogenase to oxidize alcohol at an appreciable rate.

Though alcohol affects every organ of the body, it’s most dramatic impact is upon the liver. The liver cells normally prefer fatty acids as fuel, and package excess fatty acids as triglycerides, which they then route to other tissues of the body. However, when alcohol is present, the liver cells are forced to first metabolize the alcohol, letting the fatty acids accumulate, sometimes in huge amounts. Alcohol metabolism permanently changes liver cell structure, impairing the liver’s ability to metabolize fats. This is why heavy drinkers develop fatty livers.

The liver can deal with about ½ ounce of ethanol per hour (about one drink, depending on a person’s body size, food intake, etc.). If more alcohol arrives in the liver than the enzymes can handle, the excess alcohol travels to all parts of the body, circulating until the liver enzymes are finally able to process it.

If you are looking after your liver, then it pays to not drink alcohol!

For people with Gilbert’s Syndrome alcohol will likely raise bilirubin levels, and can result in a hangover that’s pretty quick to appear and may last for days.

Gilbert’s Syndrome and medication processing

http://www.sydpath.stvincents.com.au/tests/Gilberts.htm

Recently evidence suggests that people with Gilbert’s syndrome may show increased toxicity compared to unaffected individuals following use of medications which are metabolised by glucuronidation in the liver. This has been reported with some anti-cancer agents and also with paracetamol, where they may be more prone to toxicity after paracetamol overdose.