Gene mutation may have effect on benefit of aspirin use for colorectal cancer

June 25, 2013

In two large studies, the association between aspirin use and risk of colorectal cancer was affected by mutation of the gene BRAF, with regular aspirin use associated with a lower risk of BRAF-wild-type colorectal cancer but not with risk of BRAF-mutated cancer, findings that suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin, according to a study in the June 26 issue of JAMA.

Colorectal is a leading cause of cancer-related death worldwide. have demonstrated that use reduces the risk of colorectal cancer, according to background information in the article. has suggested that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type (the typical form of a gene as it occurs in nature) neoplastic cells.

Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute, Boston, and colleagues examined the association of aspirin use with the risk of colorectal cancer according to BRAF mutation status. The researchers collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 2006 for and until January 2012 for .

Among 127,865 individuals, 1,226 incident rectal and colon cancers were identified with available molecular data. The researchers found that regular aspirin use was associated with a significantly lower risk (27 percent) of BRAF-wild-type cancer. Regular aspirin use was not associated with a lower risk of BRAF-mutated cancer. "The association of aspirin use with colorectal cancer risk differed significantly according to BRAF mutation status."

The authors also observed a lower risk of BRAF-wild-type cancer with increasing aspirin tablets per week; however, there was not a significant trend in risk reduction for BRAF-mutated cancer. "The association of aspirin tablets per week with cancer risk differed significantly by BRAF mutation status. Compared with individuals who reported no aspirin use, a significantly lower risk of BRAF-wild-type cancer was observed among individuals who used 6 to 14 tablets of aspirin per week and among those who used more than 14 tablets of aspirin per week."

In addition, longer duration of aspirin use was associated with significant risk reduction for BRAF-wild-type cancer, whereas duration of aspirin use was not significantly associated with BRAF-mutated .

"There was no statistically significant interaction between post-diagnosis aspirin use and BRAF mutation status in colorectal cancer-specific or overall survival analysis. This suggests that the potential protective effect of aspirin may differ by status in the early phase of tumor evolution before clinical detection but not during later phases of tumor progression," the authors write.

"The identification of specific cancer-subtypes that are prevented by aspirin is important for several reasons. First, it enhances our understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects. Second, development of clinical, genetic, or molecular predictors of specific subtypes of colorectal cancer might lead to the development of more tailored screening or chemo-preventive strategies. Nevertheless, given the modest absolute risk difference, further investigations are necessary to evaluate clinical implications of our findings. Lastly, our data provide additional support for a causal association between aspirin use and risk reduction for a specific subtype of colorectal cancers. Accumulating evidence supports preventive effect of aspirin against colorectal cancer."

In an accompanying editorial, Boris Pasche, M.D., Ph.D., of the University of Alabama at Birmingham, (and JAMA contributing editor), comments on the findings of this study.

"Nishihara el al derived their report from the Nurses' Health Study and the Health Professionals Follow-up Study, which include a large number of female and male health professionals. This population is predominantly white: 98 percent of the participants in the Nurses' Health Study and 95 percent of participants in the Health Professionals Follow-up Study are of a non-Hispanic white ethnic background. However, black individuals have the highest incidence of colorectal cancer in the United States and represent the ethnic group for whom colorectal cancer prevention may have the greatest benefit. Therefore, it will be important to determine whether the findings reported by Nishihara et al are confirmed in black individuals."

"In summary, these results identify biomarkers of response to aspirin administered either preventively or therapeutically and are likely to help tailor the use of aspirin in the prevention and treatment of ."

Explore further: Genes may determine aspirin's effect on advanced colon cancer

More information: JAMA. 2013;309(24):2563-2571
JAMA. 2013;309(24):2598-2599

Related Stories

Genes may determine aspirin's effect on advanced colon cancer

October 24, 2012
(HealthDay)—For patients suffering from advanced colorectal cancer, aspirin may prolong their lives if their tumor has a certain gene mutation, a new study finds.

Aspirin may lower melanoma risk

March 11, 2013
A new study has found that women who take aspirin have a reduced risk of developing melanoma—and that the longer they take it, the lower the risk. The findings suggest that aspirin's anti-inflammatory effects may help protect ...

Eligibility for aspirin for primary prevention in men increases when cancer mortality benefit added

June 6, 2013
While aspirin has been shown to be effective in preventing heart attacks in men, it also increases the risk of gastrointestinal bleeding and possibly stroke, even at low doses. As such, national guidelines suggest that aspirin ...

Study adds to evidence daily aspirin linked to lower cancer mortality

August 10, 2012
A large new observational study finds more evidence of an association between daily aspirin use and modestly lower cancer mortality, but suggests any reduction may be smaller than that observed in a recent analysis. The study, ...

Should aspirin be used to prevent cancer?

October 1, 2012
Aspirin, the everyday drug taken by countless people around the world to ward off pain and reduce their risk of developing heart disease, may have a new trick up its sleeve –-preventing cancer.

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.