mercredi 2 juin 2010

New Genetic Associations Revealed for Nasopharyngeal Carcinoma

Source: spittoon

Nasopharyngeal cancer (NPC) arises in the upper part of the throat, behind the nose. It is rare in most areas of the world—affecting only about 1 in every 100,000 people—but about 25 times more common in southern China, earning it the name “Cantonese Cancer.” NPC rates are also high in southeastern Asia, northern Africa and the Arctic.

Environmental factors play a very large role in NPC. Smoking increases risk, as does infection with the Epstein-Barr virus. Diets high in salt cured food, which are common in many of the areas where increased rates of NPC are seen, have also been shown to increase risk. These foods can be very high in nitrates and nitrites, which react with protein to form DNA-damaging chemicals.

It’s also been known for quite some time, however, that genetics contribute to NPC susceptibility. In 1970s, certain immune markers were associated with increased risk. Now a large genomewide association study has revealed three more immune related areas of the genome that are associated with risk for NPC. These results, published online this week in the journal Nature Genetics, could eventually help develop models for prediction and screening, which in turn would help with early diagnosis.

Researchers from Singapore, China and the United States studied about 5,000 people with NPC and 5,000 controls, as well as more than 250 families, all of southern Chinese descent. As expected, a strong genetic effect was seen in areas of the genome that encode the previously identified immune markers. But variants in three other regions were also associated with NPC risk. Two of these associations were statistically significant. The third SNP did not make the cut off, but was highly suggestive.

(23andMe Complete Edition customers can check their data for these SNPs using the links in the table at the end of this post.)

The statistically significant genetic associations variants were in the TNFRSF19 and MDS1-EVI1 genes. Previous research has shown that these genes encode proteins that may be involved in the body’s response to Epstein-Barr virus infection, possibly providing a neat connection between the new findings and a known environmental risk factor for NPC.

The third association was with a variant near the CDKN2A and CDKN2B genes. This gene cluster is deleted in about 40% of NPC tumors, suggesting that they are crucial for preventing cancerous growth. Additionally, this same SNP CDKN2A/CDKN2B SNP associated with NPC risk has been linked to glioma in European populations.

All of the genes identified in this study—TNFRSF19, MDS1-EVI1 and CDKN2A/CDKN2B—have previously been shown to be involved in leukemia. This suggests that there might be common disease mechanisms between that disease and NPC. Significantly, leukemia is found at higher than average rates in people with NPC.

According to the authors, the next step for research is to investigate the interactions between the genetic susceptibility factors identified by them and others with the environmental risk factors known to influence NPC.

SNP Gene Less Common Version Effect on Odds of NPC of Less Common Version
rs9510787 TNFRSF19 G 1.2
rs6774494 MDS1-EVI1 G 0.84
rs1412829* CDNK2A/CDNK2B G 0.78

* The association of this SNP with NPC was not statistically significant, but was highly suggestive.

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