Three new genetic links to colorectal cancer


Dec. 23, 2012 ? Vanderbilt-Ingram Cancer Center investigators have identified 3 new genetic “hotspots” related to colorectal cancer.

These variants, reported Dec. 23 in an Advanced Online Publication in Nature Genetics, yield new discernment into a biology of colorectal cancer — and could paint new healing targets for a disease.

Colorectal cancer is one of a many ordinarily diagnosed cancers worldwide — and rates are quite high in a United States and other grown countries. Genetics plays an critical purpose in both occasionally and patrimonial (inherited) forms of a disease. However, usually about 6 percent of colorectal cancer cases are explained by a singular genetic variants famous to consult high risk of colorectal cancer (as seen in patrimonial forms of a disease).

Previous studies on a genetic basement of colorectal cancer have pinpointed several additional variants, though many of a studies were conducted in European/Caucasian populations.

“Looking during opposite racial groups is critical since a genetic structures can be opposite adequate that variants identified in one race do not explain risk in other populations,” pronounced Wei Zheng, M.D., Ph.D., MPH, an Ingram Professor of Cancer Research and comparison author on a study. “Because of a disproportion in genetic structures and underlying sourroundings exposures, it competence be easier to learn some risk variants in studies conducted in non-European populations.”

In 2009, Zheng and colleagues in several Asian countries determined a “Asia Colorectal Cancer Consortium” to hunt for novel genetic risk factors for a disease. The consortium enclosed populations in China, Korea and Japan.

Using an proceed famous as a “genome-wide organisation study” (or GWAS), Zheng and colleagues began acid for common variants related to illness risk.

From genomic information performed from 2,098 colorectal cancer cases and 5,749 controls, a researchers identified 64 variants, or “single nucleotide polymorphisms” (SNPs), that were compared with colorectal cancer.

The investigators afterwards replicated these commentary in another set of samples, squeezing down a series of disease-associated variants to four. Three of those 4 variants were also compared with colorectal cancer risk in a incomparable European sample.

“The commentary from this investigate are applicable to both Asian and European populations,” pronounced Zheng. “Interestingly, these 3 ionization loci were not detected in prior studies conducted in European-ancestry populations.”

This investigate highlights a significance of conducting genetic studies in non-European populations to entirely expose a genetic basement for common diseases, including colorectal cancer, Zheng noted.

While a specific functions of these newly identified ionization loci are not transparent yet, several critical genes are located in a regions nearby a risk variants detected in this study. For example, one risk various is located nearby CCND2, a gene encoding cyclin D2, a member of a cyclin family of proteins that umpire a dungeon cycle. Cyclins have been related to cancer, though investigate on a CCND2 gene has been limited. Therefore, a stream commentary advise a need for serve investigate on a purpose of other cyclins and cyclin-dependent kinases in carcinogenesis.

“These new discoveries are really exciting,” Zheng said. “They will positively lead to destiny studies per a biology of these regions and a translational intensity of these commentary in cancer impediment and treatment.”

The investigate was upheld in partial by grants from a National Cancer Institute (CA070878, CA082729, CA124558, CA148667 and CA122364) of a National Institutes of Health.

Zheng is also a highbrow of Medicine, executive of a Vanderbilt Epidemiology Center, and arch of a Division of Epidemiology during Vanderbilt University.

Other Vanderbilt authors on a paper were: Ben Zhang, Ph.D.; Qiuyin Cai, M.D., Ph.D.; Jirong Long, Ph.D.; Jiajun Shi, Ph.D.; Wanqing Wen, M.D., MPH; Gong Yang, M.D., MPH; Ryan Delahanty, Ph.D., and Xiao-Ou Shu, M.D., Ph.D.

This investigate was conducted in partnership with investigators from Sun Yat-sen University Cancer Center (China), Aichi Cancer Center Research Institute (Japan), Korean National Cancer Center (South Korea), a Shanghai Cancer Institute (China), Yonsei University (South Korea), Hallym University College of Medicine (South Korea), National Cancer Institute (USA), Kyoto University Center for Genomic Medicine (Japan), and Seoul National University College of Medicine (South Korea).

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The above story is reprinted from materials supposing by Vanderbilt University Medical Center, around EurekAlert!, a use of AAAS.

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Journal Reference:

  1. Wei-Hua Jia, Ben Zhang, Keitaro Matsuo, Aesun Shin, Yong-Bing Xiang, Sun Ha Jee, Dong-Hyun Kim, Zefang Ren, Qiuyin Cai, Jirong Long, Jiajun Shi, Wanqing Wen, Gong Yang, Ryan J Delahanty, Bu-Tian Ji, Zhi-Zhong Pan, Fumihiko Matsuda, Yu-Tang Gao, Jae Hwan Oh, Yoon-Ok Ahn, Eun Jung Park, Hong-Lan Li, Ji Won Park, Jaeseong Jo, Jin-Young Jeong, Satoyo Hosono, Graham Casey, Ulrike Peters, Xiao-Ou Shu, Yi-Xin Zeng, Wei Zheng. Genome-wide organisation analyses in easterly Asians brand new ionization loci for colorectal cancer. Nature Genetics, 2012; DOI: 10.1038/ng.2505

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Source: Health Medicine Network