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Study in East Asians identifies genes tied to colon cancer risk

Aug. 21, 2014, 10:06 AM

Wei Zheng, M.D., Ph.D., right, Ben Zhang, M.D., Ph.D., MPH, and colleagues are studying genetic factors for colorectal cancer among East Asians. (photo by Anne Rayner)

Colorectal cancer is one of the leading causes of death among populations around the world. While diet, physical activity and other lifestyle factors can influence the risk of developing the disease, hereditary factors also play an important role.

Genetic factors identified to date explain only a small fraction of colorectal cancer (CRC), and most studies of hereditary risk have been conducted among people of European descent.

“It is important to conduct studies in different populations because the genetic structure may differ enough that some genetic risk variants identified in one population may not be related to the risk in other populations,” said Wei Zheng, M.D., Ph.D., Ingram Professor of Cancer Research and senior author of a new Vanderbilt-led study of East Asians published in Nature Genetics.

Zheng and his colleagues hypothesized that East Asians might be a particularly suitable population to study for genetic factors for CRC since they are less likely than people in the United States and European countries to receive CRC screening, which includes removal of polyps or other premalignant lesions that can lead to CRC.

Early detection and disease prevention may keep otherwise genetically susceptible individuals from being included in CRC population studies.

For the new investigation, researchers conducted a genome-wide association study of CRC among East Asians, including 14,963 cancer patients and 31,945 control subjects. The investigators identified six novel genetic loci that are associated with an increased risk of colorectal cancer among East Asians and suggestive evidence for three additional genetic loci.

“Genetic loci” refers to the location on a chromosome of genes and/or other DNA sequences. The investigators then collaborated with three research consortia conducted in European descendants and found that most of these newly identified risk variants also showed an association with CRC risk in European populations. Therefore, the results from the new studies are relevant to both Asian and European populations, Zheng noted.

Two of the genetic loci are linked to the genes TCF7L2 and TGFB1 that have established roles in the development of colorectal tumors. Four others are located in or near genes involved in cell signaling, growth, differentiation, motility and metastasis.

“Our findings provide additional insight into the genetics and biology of CRC,” said Ben Zhang, M.D., Ph.D., MPH, research assistant professor of Medicine and first author of the paper. “Newly identified regions may harbor potential targets for future novel cancer therapies, and genetic risk variants could be used for disease risk prediction.”

The new research was conducted as part of the Asia Colorectal Cancer Consortium, established in 2009, that includes population studies in China, Korea, Japan and Singapore. In a previous paper, also published in Nature Genetics, the group had reported the discovery of three genetic regions associated with CRC risk.

Vanderbilt investigators involved in the new research include Qiuyin Cai, M.D., Ph.D., Jirong Long, Ph.D., Jiajun Shi, Ph.D., Wanqing Wen, M.D., MPH, Gong Yang, M.D., MPH, Yanfeng Zhang, Ph.D., Chun Li, Ph.D., Bingshan Li, Ph.D., Yan Guo, Ph.D., and Xiao Ou Shu, M.D., Ph.D., MPH.

Funding for the study included grant support from the National Institutes of Health (NIH – R37CA070867, R01CA124558, R01CA148667, R01CA082729, UM1CA173640), and Ingram Professorship and Research Reward funds from the VU School of Medicine.

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