Bernard Friedenson
It is not known why some inherited cancer gene mutations seem to cause cancer only in certain characteristic organs. Women who inherit a defective BRCA1 or BRCA2 gene inherit risks for breast and ovarian cancer that seem so specific and so high that some carriers have prophylactic surgery. To find other preventive options, this analysis investigated whether chronic infections and inflammation target breast and ovary for inherited cancers. Risks for cancers with well-known links to chronic infection and inflammation were statistically evaluated for carriers of mutations in BRCA1/2 or in related proteins from published studies. Summary risks for known infection/inflammation related cancers were hundreds of times above controls for homozygotes and up to over four times above controls for heterozygotes. Evidence was also found supporting the idea that inflammation targets breast and ovary for hereditary cancers. For example, inflammation precedes hereditary breast cancers; is more pronounced in hereditary breast cancers vs. sporadic breast cancers; accompanies transitions from benign to malignant breast disease; but blocking inflammation reduces these risks. It is well known that chronic inflammation is associated with cancer. A new finding here is that cancer risks from chronic inflammation are inordinately increased in those inheriting a mutation that disables BRCA1, BRCA2, or related proteins. These increased risks can be so large that the tissue specificity for infection or inflammation effectively determines the site for cancer. This gives added importance to research identifying inflammatory processes in mutation carriers. Limiting chronic infections and inflammation may delay or prevent some hereditary cancers.
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