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How Does Night Shift Work Impact Health?

Did you know that our ancestors were nocturnal? They used to stay awake in the night to hunt without worrying about dangerous predators and sleep during the day. Now, our circadian rhythms are lined up with the sun. That's why as soon as the sun sets, our bodies start getting ready for rest, and we end up feeling sleepy.

Circadian rhythms are biological cycles that coordinate essential mental and physical functions, such as sleep and hunger. The circadian clock is regulated by a part of the brain called the Suprachiasmatic Nucleus (SCN). 

The circadian clock is also influenced by temperature. When the body temperature drops around the afternoon and late evening, it induces drowsiness and sleep. 

Sleep is induced by a hormone called melatonin, which is produced in low-light conditions. Bright light conditions during the day suppress melatonin production and promote wakefulness.

People who work the night shift have disrupted circadian rhythm and have an increased risk for the following conditions:

Working the night shift is carcinogenic to humans, according to multiple studies conducted the world over. 

Several studies show that disruption in the night’s sleep can reduce melatonin levels and increase the risk of tumor growth.

Night Shift Work—A Risk Factor for Breast Cancer

Some animal studies have shown that exposure to light at night led to the growth of breast cancer.

The risk of breast cancer among nurses and other night-shift workers seems to be higher than their counterparts who worked day shifts. 

For every five years a woman worked the night shift, her risk of developing breast cancer increased by as much as 3.3%

A study published in the Journal of National Cancer Institute in 2001 reported that women who work in rotating night shifts for at least three nights per month, along with day shifts, have a moderately high risk of breast cancer.

Further, the risk seems to be higher when the night shifts per week increase!

This increased risk is attributed to the messed-up melatonin levels in the body.

In addition to promoting sleep, melatonin also stops tumor growth and protects against the spread of cancer cells.

When melatonin levels decrease in the body, it results in an imbalance of inflammatory cytokines, increased mutations in the cells, and oxidative damage (due to free radicals)

These events can all trigger cancer development. 

A reduction in melatonin also affects estrogen levels, which further increases the risk of breast cancer.

How Does Genetics Influence Rotating Night Shift Work and Breast Cancer Risk?

A long duration of shift work throughout the years is associated with estrogen and progesterone-positive tumors.

When the circadian rhythm is altered, it changes the expression of the CLOCK genes. This also influences the production of reproductive hormones. 

The NPAS2 Gene

The Neuronal PAS Domain Protein 2 or NPAS2 gene is the largest circadian gene. It plays a vital role in sleep homeostasis and circadian rhythm regulation. 

This gene also regulates the cell cycle and works with certain other genes for repairing DNA. The NPAS2 gene shows a strong association with breast cancer.

rs2305160 (Ala394Thr) is an SNP (Single Nucleotide Polymorphism) in the NPAS2 gene. 

Among women with little or no exposure to shift work, the A allele (AA or AG) is associated with a significantly lower risk of breast cancer. 

However, among women with AA genotype who had worked >2 years of rotating night shifts, the risk of breast cancer was nearly 3 fold compared to women with the same genotype with <2 years of night shift work.

GenotypeImplication - > 2 years of rotating night shifts
AA (Thr/Thr)~3 fold increased risk of breast cancer
AG (Thr/Ala)Slightly increased risk of breast cancer
GG (Ala/Ala)Normal risk of breast cancer

Use Xcode Life’s Free Gene Tool To Find Out If You Have The Risk Genotype!

The RORA Gene

RAR-Related Orphan Receptor A or the RORA gene is located on chromosome 15 and regulates genes involved in the body’s circadian rhythm.

rs1482057 is an SNP in the RORA gene. A study published in 2014 showed that SNP rs1482057 was associated with breast cancer in postmenopausal women

Women who have at least one A allele and had a history of working night shifts in their lifetime had a higher risk of developing breast cancer

Conversely, women having the CC genotype and working night shifts showed a decreased risk of breast cancer.

AAIncreased breast cancer risk on night shift work
ACIncreased breast cancer risk on night shift work
CCDecreased breast cancer risk on night shift work

The CRY2 Gene

Cryptochrome circadian regulator 2 or the CRY2 gene gives instructions to produce a protein involved in regulating the body’s circadian rhythm.

rs2292912 is an SNP in the CRY2 gene, located on chromosome 11. Night shift working increased the risk of breast cancer in women who carried the CG genotype of rs2292912 SNP.

CGIncreased breast cancer risk on night shift work
GGDecreased breast cancer risk on night shift work
CCDecreased breast cancer risk on night shift work

Regulating Your Sleep-Wake Cycle To Reduce Breast Cancer Risk

Since working night shift hours increases the risk of breast cancer in women, one of the most effective ways to lessen this risk is to reduce working night shifts. 

Switching with a colleague’s shift, alternating your night shifts with day shifts, or switching jobs can be a few ways by which you can reduce your night shift hours.

Apart from disrupting the sleep-wake cycle, disturbed sleep or poor quality of sleep in people who work night shifts can increase their risk for breast cancer. 

So, if you are working a night shift, ensure you get your 7-8 hours of sleep every day. If you have trouble sleeping, consult your doctor about supplements that can help you catch up on your daily sleep.

People working the night shift must try and reduce other risk factors of breast cancer. 

A healthy diet with lots of fruits, limited alcohol consumption and smoking, adequate physical activity, and reduced exposure to harmful chemicals can help reduce breast cancer risk. 


  1. The circadian rhythm regulates our body’s sleep-wake cycle.
  2. A disturbed circadian rhythm increases the risk of developing health conditions like obesity, cardiovascular diseases, gastrointestinal problems, etc.
  3. According to many studies and published reports, working the night shift is carcinogenic as it decreases melatonin production - melatonin helps stop tumor growth.
  4. Working the night shift has been particularly associated with an increased risk for breast cancer.
  5. Women with certain changes in genes like NPAS2, RORA, and CRY2 have an increased risk of breast cancer when on rotating night shifts.
  6. Regulating your sleep-wake cycle, getting adequate sleep, following a healthy diet, and limiting alcohol consumption and smoking can help lower breast cancer risk. 


What does the CYP1A2 gene do? 

CYP1A2 codes for the production of 21-hydroxylase, which is part of the cytochrome P450 family of enzymes.

This family of enzymes is quite important as it is a part of many processes, that include breaking down drugs, production of cholesterol, hormones, and fats.

The adrenal glands secrete the enzyme, 21-hydroxylase.

Situated on the top of the kidneys, the adrenal glands also produce hormones like epinephrine and cortisol.

Incidentally, 21-hydroxylase plays a role in the production of cortisol and another hormone named aldosterone.

Cortisol is a stress-related hormone and plays a role in protecting the body from stress, as well as reducing inflammation.

Cortisol also helps in maintaining blood sugar levels.

Aldosterone, also known as the salt-retaining hormone, regulates the amount of salt retained in the kidneys.

This has a direct consequence on blood pressure, as well as fluid retention in the body. 

There seems to be an interesting trend in the activity of the CYP1A2 gene and caffeine intake.

The consequence of being a “rapid” or a “slow” metabolizer of caffeine can have effects on an individual’s cardiovascular health.

This article explains the wide-ranging effects of this gene, caffeine intake,  cardiovascular health, hypertension, and even pregnancy!

What is the association between CYP1A2 and caffeine metabolism?

In the body, CYP1A2 accounts for around 95% of caffeine metabolism.

The enzyme efficiency varies between individuals.

A homozygous, that is, AA genotype represents individuals that can rapidly metabolize caffeine.

Some individuals have a mutation in this locus and thus have the AC genotype.

These individuals are “slow” caffeine metabolizers.

CYP1A2 and cardiovascular health

There seems to be a link between CYP1A2, the incidence of myocardial infarction (MI), and coffee intake.

The positive effects of coffee include lowering a feeling of tiredness and increasing alertness; however, it can also narrow the blood vessels.

This increases blood pressure and could lead to cardiovascular disease risk.

Rapid metabolizers of coffee have the AA genotype and may unravel the protective effects of caffeine in the system.

However, the individuals that are slow metabolizers have a higher risk of MI.

This suggests that the intake of caffeine has some role in this association. 

Yet another study associated DNA damage due to mutagens found in tobacco smoking could contribute to MI.

The study included participants who were genotyped at the CYP1A2 gene.

They found a group of ‘highly inducible’ subjects that had a CYP1A2*1A/*1A genotype.

These individuals have a greater risk for MI, independent of their smoking status.

This also means that there is some intermediary substrate that the CYP1A2 gene decomposes, and if this gene has a mutation, it could lead to a higher risk of MI. 

In a study conducted on 2014 people, people who were slow metabolizers of caffeine (C variant) and who consumed more than 3 cups of coffee per day had an association with increased risk for myocardial infarction. 

In a similar study on 513 people, increased intake of coffee, among slow metabolizers, has an association with an increased risk for hypertension.

The association between smoking and hypertension

Smoking is capable of inducing the CYP1A2 enzyme. Smokers exhibit increased activity of this enzyme.

In a study conducted on 16719 people, people with the A variant, and who were non-smokers, were 35% less likely to be hypertensive than people with the C variant.

In the same study, CYP1A2 activity had a negative association with blood pressure among ex-smokers.

But for people who were still smoking, the same gene expressed an association with increased blood pressure.

The gene CYP1A2 also has an association with caffeine metabolism and smoking.

A study aimed to tie these concepts together to find the relationship between this gene and blood pressure (BP).

The main measurements of the study were caffeine intake, BP, and the activity of the CYP1A2 gene.

In non-smokers, CYP1A2 variants (having either a CC, AC, or AA genotype) were associated with hypertension.

Higher CYP1A2 activity was associated with people who quit smoking and had lower BP compared to the rest but had a higher BP while smoking.

In non-smokers, CYP1A2 variants (having either a CC, AC or AA genotype) were associated with high caffeine intake, and also had low BP.

This means that caffeine intake plays some role in protecting non-smokers from hypertension, by inducing CYP1A2.

The effect of the CYP1A2 on pregnancy and caffeine intake

The intake of caffeine during pregnancy has an association with the risk of reduced fetal growth.

High caffeine intake shows a link to decreased birth weight.

The babies are also at risk of being too small during the time of pregnancy.

This was also observed in a study conducted on 415 Japanese women.

Women with the A variant who drank more than 300 mg of coffee per day were shown to be at an increased risk of giving birth to babies with low birth weight.


In conclusion, there are a lot of effects that the CYP1A2 gene has on the body. Many studies, as noted above, seem to link the activity of this gene to caffeine intake.

A variant at the CYP1A2 gene can determine whether an individual is a fast or slow metabolizer of caffeine, and this has some effect on the blood pressure and cardiovascular health of an individual.

The gene also plays a role in regulating an infant’s weight during the pregnancy of a woman,  and this has a link with caffeine intake. It is thus interesting to analyze the effect of the variants of the CYP1A2 gene on an individual, based on their caffeine intake. 



Do you have your DNA raw data from 23andMe, AncestryDNA, FTDNA, LivingDNA, etc.?

Upload it to Xcode Life to know about your CYP1A2 caffeine metabolism and caffeine sensitivity variants.

Published on 18 June, 2020

It is hard to believe that caffeine, a stimulant that holds popularity in battling fatigue and improving creativity, can do any harm.

1. Caffeine Sensitivity

Caffeine sensitivity is a term that describes the efficiency of the human body to process caffeine and to metabolize it.

We have all heard of co-workers who drink 6 cups of coffee, the recreational drink for nearly 60% of Americans, every day, and friends who guzzle a cup an hour before bedtime.

Yet there are some of us who feel jittery, anxious, or even restless after a single cup.

So, is caffeine a scourge, a tonic, or a mix of both?

Is coffee good for you?

For starters, coffee has a few benefits.

A large research study showed that Americans get more antioxidants from coffee than from any other dietary source.

Other studies have shown that there are several nutrients in a cup of brewed coffee, like Magnesium, Niacin, and Potassium, depending on the soil nutrients and the type of processing.

2. How caffeine works

Adenosine is an organic compound that inhibits arousal and promotes sleepiness upon binding to its receptor.

Caffeine has a structure similar to adenosine and works as an adenosine receptor antagonist.

It competes with adenosine to bind to the adenosine receptor.

This process promotes wakefulness.

Though this can affect the quality of sleep among certain people, it could help in situations like driving at night or averting jet lag, where mental alertness is critical.

Analyze Your Genetic Variants For Caffeine Sensitivity

According to the U.S. Food and Drug Administration (FDA), 300 milligrams of caffeine are consumed every day by the average American. The Mayo Clinic states that drinking up to 400 milligrams per day is safe, which is approximately 4 cups.

A good cup of coffee is the most popular caffeine delivery mechanism that comes with a few health benefits like being a good source of antioxidants, warding off liver disease, and protecting against Parkinson’s.

The health risks and benefits have been understood, over the years, however, caffeine and metabolism, or the way in which our body processes the chemical, varies on several key factors.

3. Caffeine content in popular beverages

BeverageCaffeine content (mg)
Coffee8 oz cup - 95 mg
Espresso1 oz shot - 63 mg
Green tea8 oz cup - 28 mg
Black tea8 oz cup - 26 mg
Energy drinks8 oz cup - 91 mg
Sodas (Cola)16 oz cans - 49 mg
Coffee liqueur1.5 oz shot - 14 mg
Dark chocolate1 oz square 24 mg

4. Caffeine Metabolism: What CYP1A2 gene says

Caffeine, an alkaloid, is also known as  1,3,7-trimetilksantin.

It is acidic in its pure crystalline form and is found in over 60 plant species.

The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.

Due to potentially ineffective CYP1A2 enzyme activity, some people can experience issues like caffeine jitters after 2-3 cups of coffee per day.

Such slower metabolizers of caffeine may experience problems with blood pressure, headaches, etc.

Learn More

<strong>Coffee and <em>CYP1A2</em>: 3 ways high caffeine intake can affect you!</strong>

5. More about the CYP1A2 gene

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene have an association with the efficiency of caffeine metabolism.

Some people have a genetic predisposition to produce very little of CYP1A2 enzyme while others may produce a large amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

Analyze Your Genetic Variants For Caffeine Sensitivity

Approximately 10% of the population are found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

6. Slow metabolizer variant

The polymorphism associated with caffeine metabolism is rs762551.

Studies have shown that individuals with AC or CC genotypes are slow metabolizers of caffeine.

These individuals have a high caffeine sensitivity.

They tend to have a slightly increased risk for heart attack upon consumption of more than 2 cups of coffee every day.

7. Rapid metabolizer variant

Individuals who have the A.A. genotype in the specific polymorphism of the CYP1A2 gene may be fast metabolizers.

These individuals have a low caffeine sensitivity.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased caffeine consumption.

8. How many cups of coffee should you consume? Genetic testing for Caffeine metabolism

The polymorphism in the CYP1A2 gene is well studied and is useful to determine the caffeine metabolism status.

This, in turn, can shine some light on the tendency to consume caffeine. 

9. 23andMe caffeine results

The 23andMe reports provide caffeine metabolizer status.

There are other well known 23andMe third-party tools, like Xcode Life, that can provide a better understanding.

Upload your 23andMe raw data to find out your caffeine metabolism status.

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23andMe DNA raw data is the genetic information obtained after a genetic test, and it is usually provided as a text file.

This information can be downloaded after utilizing the 23andMe login provided to all 23andMe customers.

10. Using your Ancestry DNA raw data to identify your caffeine metabolizer status

There is a wealth of information provided by ancestry DNA that can be used to identify a number of health and nutrition-based traits.

Use your ancestry DNA login to download your Ancestry DNA raw data.

You can then upload your Ancestry DNA raw data onto our site to identify the caffeine metabolizer status.

11. 23andme vs. AncestryDNA vs. Xcode Life

23andme vs. AncestryDNA vs. Xcode Life pertaining to caffeine metabolizer status

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12. Your genetic predisposition to consume caffeine

People of certain genetic types tend to have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the caffeine metabolism status of the individual.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

Updated on 10 June, 2020

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