Few DNA repair gene variants associated with increased cancer risk
An atypical prion strain of mad cow disease, also called bovine spongiform encephalopathy or BS, is more virulent than the classical strain, according to a researcher who spoke Nov. 14 at Kansas State University. Qingzhong Kong from Case Western Reserve University presented “Chronic Wasting Disease and Bovine Spongiform Encephalopathy: Public Health Risk Assessment” at the
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Variants of numerous DNA repair genes initially appeared to be statistically significantly associated with cancer risk in epidemiological studies.
When the data from individual studies are pooled, however, few DNA repair gene variants appear truly associated with increased cancer risk, according to a field synopsis published in the December 30 online issue of the Journal of the National Cancer Institute.
Because DNA damage is associated with cancer development, researchers hypothesized that genes required for DNA repair may influence risk of cancer. Initial reports supported the idea. A comprehensive review of the data has not been available previously.
In the current study, John P. Ioannidis, M.D., of the University of Ioannina School of Medicine in Greece, and colleagues identified 241 previously reported associations between gene variants and the risk of cancer. The team pooled the data from 1,087 data sets and reexamined these associations.
Initially 31 of the 241 associations appeared to be statistically significantly associated with cancer risk in the meta-analysis. However, only two remained statistically significant after the researchers adjusted for multiple comparisons. An XRCC1 allele (-77 T>C) and an allele of ERCC2 (codon 751) were associated with lung cancer risk.
“The lack of many signals with strong credibility that emerged from our analysis, despite an enormous amount of work in this area over the years, needs careful consideration,” the authors write. “The ability of the candidate gene approach to identify genetic risk factors may have been overestimated. Alternatively, the importance of the DNA repair pathway may have been exaggerated. However, there is increasing recognition that genetic risks of cancer conferred by single variants are almost always very modest. This means that even if the DNA repair pathway is essential for carcinogenesis, extremely large-scale evidence would be necessary to establish with high confidence the presence of specific associations.”
In an accompanying editorial, Ajay Yesupriya, of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention in Atlanta, and colleagues describe an international collaboration of researchers called the Human Genome Epidemiology Network (HuGENet) that advocates a concerted approach to conducting meta-analyses and systematic reviews of literature on gene-disease association studies. The paper by Ioannidis and colleagues is the first HuGENet Field Synopsis on cancer susceptibility.
“The identification of reliable genetic associations is fundamental to the translation of genomic research findings to clinical and public health applications,” the editorialists write. “By synthesizing research findings and assessing cumulative evidence, field synopses can recognize the most credible genetic associations.”
Abnormalities in genes that repair mistakes in DNA replication may help identify people who are at high risk of developing pancreatic cancer, a research team from The University of Texas M. D. Anderson Cancer Center reports in the Jan. 15 issue of Clinical Cancer Research. Defects in these critical DNA repair genes may act alone
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A new study presages a real aim of genetics: to look at whole populations to in order determine the significance of individual genetic variants for individual health. The research team, whose work is published in Nature Genetics, find six novel genetic variants that are associated with lipid levels, a common indicator of heart or artery
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Cancer Research UK scientists have identified a long sought after enzyme that plays a critical role in a DNA repair pathway linked with inheritable breast and ovarian cancer, reveals research published in Nature. Familial breast cancers, such as those caused by mutation of the BRCA2 tumour suppressor, are caused by defects in a pathway that
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Latina women have a lower risk of breast cancer than European or African-American women generally, but those with higher European ancestry could be at increased risk, according to data published in the December 1 issue of Cancer Research, a journal of the American Association for Cancer Research. “We need to study the possible factors that
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