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  • American Association for Cancer Research (AACR)  (3)
  • 1
    Online Resource
    Online Resource
    Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Prevention Research Vol. 15, No. 8 ( 2022-08-01), p. 509-519
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 15, No. 8 ( 2022-08-01), p. 509-519
    Abstract: MUTYH carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C & gt;T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03–2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42–8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81–2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C & gt;T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-22-0080
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2422346-3
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  • 2
    Online Resource
    Online Resource
    Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Prevention Research Vol. 15, No. 6 ( 2022-06-02), p. 365-375
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 15, No. 6 ( 2022-06-02), p. 365-375
    Abstract: The effects of aspirin on melanoma are unclear, with studies reporting conflicting results. Data from two periods of the ASPirin in Reducing Events in the Elderly (ASPREE) study; the randomized placebo-controlled trial period examining daily 100 mg aspirin in older adults with a median follow-up of 4.7 years, and the second period, an additional 2 years of observational follow-up, were utilized in this secondary analysis to examine whether aspirin exposure is associated with a reduced cutaneous melanoma incidence. All melanoma cases were adjudicated and Cox proportional hazards models were used to compare incidence between randomized treatment groups. ASPREE recruited 19,114 participants with a median age of 74 years. During the trial period, 170 individuals (76 aspirin, 94 placebo) developed an invasive melanoma, and no significant effect of aspirin was observed on incident melanoma [HR = 0.81; 95% confidence interval (CI), 0.60–1.10]. Including the additional 2 years of observational follow-up (median follow-up of 6.3 years), 268 individuals (119 aspirin, 149 placebo) developed an invasive melanoma, and similar results were observed (HR = 0.81; 95% CI, 0.63–1.03). A reduced number of events was observed with aspirin among females in a subgroup analysis (HR = 0.65; 95% CI, 0.44–0.92); however, the interaction effect with males (HR = 0.92; 95% CI, 0.68–1.25) was nonsignificant (P = 0.17). Our findings from this randomized trial do not provide strong support that aspirin is associated with a reduced risk of invasive melanoma in older individuals. Additional studies are required to further explore this relationship. Prevention Relevance: Melanoma prevention is an important strategy to improve outcomes and while preventive efforts have largely focused on sun protection, the role of potential chemopreventive agents such as aspirin warrants investigation.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-21-0244
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2422346-3
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  • 3
    Online Resource
    Online Resource
    Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Prevention Research Vol. 15, No. 7 ( 2022-07-05), p. 447-454
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 15, No. 7 ( 2022-07-05), p. 447-454
    Abstract: Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the association between genetic susceptibility to colorectal cancer and aspirin use in a prospective study of 12,609 individuals of European descent ages ≥70 years, enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) double-blinded, placebo-controlled randomized trial (randomized controlled trial; RCT). Cox proportional hazards models were used to assess the association of aspirin use on colorectal cancer, as well as the interaction between the PRS and aspirin treatment on colorectal cancer. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident colorectal cancer. Aspirin assignment was not associated with incidence of colorectal cancer overall [HR = 0.94; 95% confidence interval (CI), 0.68–1.30] or within strata of PRS (P for interaction = 0.97). However, the PRS was associated with an increased risk of colorectal cancer (HR = 1.28 per SD; 95% CI, 1.09–1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR = 1.85; 95% CI, 1.08–3.15). In a prospective RCT of older individuals, a PRS is associated with incident colorectal cancer risk, but aspirin use was not associated with a reduction of incident colorectal cancer, regardless of baseline genetic risk. Prevention Relevance: There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older individuals outweighs the benefit. We sought to determine whether some older individuals might still benefit from aspirin based on their genetic susceptibility.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-22-0011
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2422346-3
    Location Call Number Limitation Availability
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