SNPwatch: Researchers Identify Genetic Variant That May Affect Liver Cancer Risk in Those Chronically Infected with Hepatitis B Virus

Hepatocellular Carcinoma (HCC) is the fourth most common cancer in the world. More than half a million new cases of this form of liver cancer are reported each year. Excessive alcohol consumption and obesity have long been linked to HCC, but the main cause of the disease is chronic hepatitis B virus (HBV) infection. Not everyone chronically infected with the virus, however, develops HCC.

To investigate whether genetic factors play a part in whether an HBV-infected person will go on to develop HCC, researchers analyzed the DNA of several groups of people with Chinese ancestry, as it is known that in China 80% of cases of HCC are linked to chronic HBV infection. Their results, published online this week in the journal Nature Genetics, show a strong link to a genetic variation on chromosome 1.

The sample of chronic HBV carriers used to identify the association consisted of 355 people with HCC and 360 without HCC. An additional 1,962 individuals with HCC, 1,430 control subjects, and 159 families, were also studied to confirm the results. The strongest association with increased risk for HBV-related HCC was discovered in SNP rs12136376. Overall, each copy of the less common T version of this SNP was associated with about 40% lower odds of HCC in people chronically infected with HBV.

(The strongest association found by the researchers was actually with SNP rs17401966. However, 23andMe does not currently provide data for this variant. Rs12136376 is a perfect proxy for rs17401966 in people with Chinese ancestry. 23andMe Complete Edition customers can check their data for rs12136376 using the Browse Raw Data feature.)

The researchers also explored differences in the effect of rs12136376 on HCC rates among HBV carriers of different genders and ages. They found that rs12136376 was more strongly associated with HCC in virus-infected males than females. They also found that among those who did have HCC, people carrying two copies of the protective T version of the SNP were 1.1 years older at diagnosis than carriers of two copies of a C.

Rs12136376 is near several genes: KIF1B, UBE4B and PGD. Multiple lines of evidence suggest that one or more of these genes are plausible candidates for HCC susceptibility. Changes in the region of the genome where they are found are commonly seen in many different cancers, including HCC. The KIF1B gene has been shown to be important in preventing some types of tumors, and mutations in this gene are associated with several types of cancer. UBE4B and PGD encode proteins involved in vital cellular processes that often go awry in cancer development.

For more information about Chronic Hepatitis B Infection, see the following Spittoon post:
Immune System Variations May Determine Susceptibility To Chronic Hepatitis B Infection

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.