Cancer biology: On the trail of an elusive tumor
Published online 01 September 2010
A large-scale genomic analysis yields insights into a cancer that disproportionately affects individuals from southern China
The frequency of NPC in individuals from areas of southern China, such as the city of Guangzhou, can be as high as 25 cases per 100,000 people — 25 times greater than in the rest of the world.
Nasopharyngeal carcinoma (NPC) is a form of throat cancer with an unusual degree of geographic localization that has earned it an unfortunate nickname: the ‘Canton tumor’. “It exhibits unusually high prevalence in southern Chinese descendants — mostly in southern China and Southeast Asia — with an occurrence rate about 25 times higher than that in most regions of the world,” explains Jianjun Liu from the A*STAR’s Genome Institute of Singapore.
NPC is tied to lifestyle factors, including smoking and the consumption of pickled foods, but it is also clearly linked with genetic risk factors. Several candidates have been suggested, including variations in the genes encoding several of the human leukocyte antigen (HLA) immunoregulatory factors, but there is insufficient data about the early pathology of this cancer to enable accurate, early diagnosis. Fortunately, a recent effort spearheaded by Liu and Yi-Xin Zeng at the Sun Yat-sen University Cancer Center in Guangzhou, China, has uncovered a bounty of potentially useful new genetic data that may help scientists to get a better handle on NPC pathology1.
They performed a genome-wide association study, a massive sweep of the genomes of nearly 3,500 NPC patients and unaffected controls of southern Chinese descent designed to identify seemingly minor sequence variations that might be specifically associated with cancer risk. This assessment revealed 49 potentially useful single-nucleotide polymorphisms (genetic markers), of which seven were ultimately validated as being statistically meaningful by analysis against a second, independent cohort of southern Chinese cases and controls.
“Our findings not only nailed the association between certain variations in HLA genes and NPC, which has been pointed out since the 1970s, but also identified polymorphisms in three non-HLA genes,” says Liu. These three non-HLA polymorphisms have also been linked independently to the onset of leukemia and lymphoma, suggesting that these various cancers might all be bound together by common mechanistic elements. Indeed, previous studies have already shown that NPC patients are at elevated risk for leukemia and other blood-related cancers.
Liu and Zeng plan to continue their research partnership, looking more deeply at the various candidate genes identified here while also extending their efforts to investigate other domains of the genome, and the planet. “Our purpose is to find out whether the genetic risk factors identified in southern Chinese populations also play an important role in other ethnic populations,” says Liu, “and to search for additional genetic risk factors, either common or rare, involved in the development of NPC.”
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore
- Bei, J.-X., Li, Y., Jia, W.-H., Feng, B.-J., Zhou, G., Chen, L.-Z., Feng, Q.-S., Low, H.-Q., Zhang, H., He, F. et al. A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nature Genetics 42, 599–603 (2010). | article