Differential Effects of Wine Consumption on Colorectal Cancer Outcomes Based on Family History of the Disease

Potentially favorable effects of wine consumption on colorectal cancer (CRC) incidence have been reported, but effects on clinical outcomes are unknown. This case-only analysis was designed to investigate outcomes among familial (n = 141) and sporadic (n = 358) CRC patients enrolled in the University of California Irvine CRC gene-environment study during 1994–1996 based on their reported frequency of wine consumption in the year prior to diagnosis. Cases were categorized as either regular or infrequent wine consumers. Univariate survival rate analyses were estimated using the Kaplan and Meier method and log-rank test. Multivariate survival analyses were performed using Cox proportionalhazards ratios (HRs). Earlier stage at presentation (P = 0.034) was noted for familial (but not sporadic) CRC cases reporting regular wine consumption. An overall survival (OS) benefit was observed for familial (but not sporadic) CRC cases that were regular (10-yr OS = 75%) versus infrequent wine consumers (10-yr OS = 47%; P = 0.002). This survival improvement for familial CRC cases remained after adjustment for age, stage, treatment, and other clinically relevant factors (HR = 0.50, 95% confidence interval = 0.25–0.99). Our findings implicate favorable effects of wine consumption on stage at presentation and survival in CRC, selectively among familial CRC cases.     

Inhibition of Lupus by Genetic Alteration of the Interferon-α/β Receptor

Type I interferons (IFN-αβ) are immunoregulatory cytokines that promote both innate and adaptive immune responses. Although they have been implicated in human SLE, recent studies in mice have helped solidify this connection. By using lupus-prone mice with knockout of the IFN-αβ receptor, we and others have documented that lack of IFN-αβ leads to a marked reduction in disease manifestations, including autoantibody production, target organ damage and mortality. Furthermore, IFN-αβ was found to potentially contribute to several levels of disease pathogenesis. These included the differentiation and activation of dendritic cells, the activation and proliferation of T cells, T cell survival and the activation and survival of autoantibody-producing B cells. These findings strongly support the targeting of IFN-αβ in SLE and suggest that definition of the specific pathways critical for disease induction will be important for optimal intervention.     

Unusual localization of an adenoid cystic carcinoma subsequent to superficial parotidectomy for a benign lesion

Adenoid cystic carcinoma of the parotid gland is relatively rare. According to a retrospective study of the medical records and histopathology files of 514 cases of parotid tumors operated at our hospital over a period of 18 years, adenoid cystic carcinoma represented only 2.3% of all parotid gland neoplasms, a total of 12 cases. In our records we retrieved only one documented case of adenoid cystic carcinoma that originated in the parotid gland subsequent to superficial parotidectomy for a benign lesion (pleomorphic adenoma).An even more exceptional presentation of adenoid cystic carcinoma is as a bilobed tumor extending from the post auricular to the temporal and zygomatic region. The management of this case is presented along with a brief review of the literature concerning the evaluation and management of this rare entity.     

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

Background: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure.Objective: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels.Methods: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography–tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA.Results: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration.Discussion: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174     

Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X

Context  Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective  To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants  Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures  Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results  Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). Conclusions  Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.      

Carotid endarterectomy in octogenarians: Does increased age indicate “high risk?”

OBJECTIVE: Carotid endarterectomy (CEA) is proven to be the most effective treatment for symptomatic carotid artery stenosis of 50% or greater and asymptomatic carotid stenosis of 60% or greater. Although the prevalence of carotid artery disease increases with age, most prospective and randomized trials have excluded patients older than 80 years, implying that they are either at higher procedural risk or have decreased life expectancy. Since advanced age (>/=80 years) has been viewed as a "high-risk" indicator for CEA, age >/=80 years has been used as an indication for alternative treatment. The study was conducted to determine if age >/=80 years is related to increased morbidity, mortality, and length of stay in patients undergoing CEA. METHODS: In the 12-year period from 1993 to 2004, 2217 CEAs were performed in 1961 patients. Three hundred sixty procedures were performed in 334 patients >/=80 years. Demographics, presentation, risk factors, operative outcome, and survival were analyzed. Contemporary literature was reviewed and the results summarized. RESULTS: In patients aged >/=80 years, compared with their younger cohort, there was no difference in stroke (1.1% vs 0.8%, P = .333) but there was a higher operative mortality (1.9% vs 0.8%, P = .053). The combined stroke/death rate was higher in octogenarians (3.1% vs 1.5%, P = .041). This difference was due to the greater stroke/death rate in symptomatic octogenarians vs asymptomatic octogenarians (6.0% vs 0.9%, P = .007). The average postoperative length of stay was 3.2 +/- 4.8 days for octogenarians compared with 2.4 +/- 3.5 days for their younger counterparts ( P < .001). Thirty-seven percent of the octogenarians were discharged on the first postoperative day vs 51% ( P < .001), whereas 13% remained hospitalized beyond 5 days vs 8% ( P = .003). Although Kaplan-Meier survival curves show a higher mortality in octogenarians, survival after CEA approaches that of the overall population. A summary of the contemporary literature of CEA in 2204 patients >/=80 shows an operative stroke rate of 2.23% and death rate of 1.28%, with a combined stroke/death rate of 3.51%. CONCLUSION: CEA is a safe and effective procedure in the octogenarian. The combined stroke/death rate is increased in patients aged >/=80, indicating increased risk, predominantly in symptomatic patients. Although CEA risk in octogenarians is higher compared with a younger cohort, outcomes remain within acceptable national guidelines and within outcome measures known to confer benefit compared with best medical care. Therefore, the term "high risk" should not be arbitrarily applied to patients reaching the 80-year threshold. This is confirmed by the contemporary literature.