NEW DELHI, Dec 26: While it has been known that ovarian and breast cancers run in families with a history of such cancers, scientists have now pinpointed inherited genetic susceptibility of 12 cancer types.
Some portion of the risk of developing cancer is hereditary and that inherited genetic errors are very important in some cancers but much less so in others. In a new analysis, researchers have shed light on these hereditary elements across 12 cancer types – showing a surprising inherited component to stomach cancer and providing some needed clarity on the consequences of certain types of mutations in well-known breast cancer susceptibility genes, BRCA1 and BRCA2. The study has appeared in the journal Nature Communications.
The investigators analysed genetic information from more than 4,000 cancer cases included in The Cancer Genome Atlas project, an initiative of the US National Institutes of Health (NIH), to unravel the genetic basis of cancer.
“In general, we have known that ovarian and breast cancers have a significant inherited component, and others, such as acute myeloid leukemia and lung cancer, have a much smaller inherited genetic contribution,” said senior author Li Ding, PhD, associate professor of medicine and assistant director of the McDonnell Genome Institute at Washington University.
“But this is the first time on a large scale that we’ve been able to pinpoint gene culprits or even the actual mutations responsible for cancer susceptibility.” The new information has implications for improving the accuracy of existing genetic tests for cancer risk and eventually expanding the available tests to include a wider variety of tumours.
Past genomic studies of cancer compared sequencing data from patients’ healthy tissue and the same patients’ tumours. These studies uncovered mutations present in the tumours, helping researchers identify important genes that likely play roles in cancer. But this type of analysis can’t distinguish between inherited mutations present at birth and mutations acquired over the lifespan. In 114 genes known to be associated with cancer, they found rare germline mutations in all 12 cancer types, but in varying frequencies depending on the type.
They focused on a type of mutation called a truncation because most truncated genes can’t function at all. Of the ovarian cancer cases the investigators studied, 19 per cent of them carried rare germline truncations. In contrast, only four per cent of the acute myeloid leukemia cases in the analysis carried these truncations in the germline.
They also found that 11 per cent of the stomach cancer cases included such germline truncations, which was a surprise, according to the researchers, because that number is on par with the percentage for breast cancer. “We also found a significant number of germline truncations in the BRCA1 and BRCA2 genes present in tumour types other than breast cancer, including stomach and prostate cancers, for example,” Ding said.
The BRCA1 and BRCA2 genes are important for DNA repair. While they are primarily associated with risk of breast cancer, this analysis supports the growing body of evidence that they have a broader impact. “Of the patients with BRCA1 truncations in the germline, 90 per cent have this BRCA1 truncation enriched in the tumour, regardless of cancer type,” Ding said.
(UNI)
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