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Ovarian Cancer’s Genetic Relationship to Other Cancers

By: Celeste L. Dixon
Posted: Wednesday, May 8, 2019

Utilizing the latest sophisticated statistical models and wide-ranging genetic data, a research team’s study results reveal that numerous “solid tumors arising across tissues share in part a common germline genetic basis,” wrote Xia Jiang, PhD, of the Harvard T.H. Chan School of Public Health, Boston, and colleagues. They found a significant association between ovarian and breast cancers and a nominally significant one between ovarian and lung cancers.

The team accessed the database of summary statistics from the largest-to-date European ancestry genome-wide association study (GWAS) of ovarian, breast, colorectal, head/neck, lung, and prostate cancers. The average sample size was 49,369 cases and 50,219 controls per cancer. The work was published in Nature Communications. 

The significant GWAS loci for a particular cancer, such as ovarian cancer, explained most of its heritability. However, in some cancers, significant GWAS loci of other cancers also contributed a nontrivial part of its heritability. Significant breast cancer GWAS loci explained 10%, 15%, and 22% heritability of colorectal, ovarian, and prostate cancers, respectively, and the significant prostate cancer GWAS loci explained 11% and 15% heritability of breast and ovarian cancers, respectively.

Despite prior literature suggesting similarities between serous ovarian cancer and estrogen-receptor–negative breast cancers, “we did not observe statistically significant different genetic correlations between [estrogen-receptor–negative or –positive] breast cancer and serous ovarian cancer,” wrote the authors. “This suggests that rare high penetrance variants may play a more important role in driving the similarities behind [estrogen-receptor–negative] breast cancer and serous ovarian cancers than common genetic variation.”

Dr. Jiang and colleagues believe their results provide direction for future cross-cancer studies to generate insights into the biologic mechanisms underlying cancer development and etiology. Further work that continues to identify new susceptibility loci “could help our understanding of disease development, improve [the] prediction power of genetic risk scores, and hence contribute to screening and personalized risk prediction,” they wrote. 

Disclosure: The study authors reported no conflicts of interest.



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