Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case–control study of African Americans and whites

Abstract Introduction A polymorphism in the manganese superoxide dismutase (MnSOD) gene, Ala-9Val, has been examined in association with breast cancer risk in several epidemiologic studies. Results suggest that the Ala allele increases the risk of breast cancer and modifies the effects of environmental exposures that produce oxidative damage to DNA. Methods We examined the role of the MnSOD Ala-9Val polymorphism in a population-based case–control study of invasive and in situ breast cancer in North Carolina. Genotypes were evaluated for 2025 cases (760 African Americans and 1265 whites) and for 1812 controls (677 African Americans and 1135 whites). Results The odds ratio for MnSOD Ala/Ala versus any MnSOD Val genotypes was not elevated in African Americans (odds ratio = 0.9, 95% confidence interval = 0.7–1.2) or in whites (odds ratio = 1.0, 95% confidence interval = 0.8–1.2). Greater than additive joint effects were observed for the Ala/Ala genotype and smoking, radiation to the chest, and occupational exposure to ionizing radiation. Antagonism was observed between the Ala/Ala genotype and the use of nonsteroidal anti-inflammatory drugs. Conclusions The MnSOD genotype may contribute to an increased risk of breast cancer in the presence of specific environmental exposures. These results provide further evidence for the importance of reactive oxygen species and of oxidative DNA damage in the etiology of breast cancer

Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV

Background While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown. Methods People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6–12 months, 1–2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class. Results Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0–23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6–12 months: IR, 45.8; 95% CI, 41.4–50.19; 1–2 years: IR, 34.3; 95% CI, 31.5–37.4; and 2+ years: IR, 18.5; 95% CI, 17.4–19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. Conclusions cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk

Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV

Background. While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown. Methods. People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6-12 months, 1-2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class. Results. Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0-23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6-12 months: IR, 45.8; 95% CI, 41.4-50.19; 1-2 years: IR, 34.3; 95% CI, 31.5-37.4; and 2+ years: IR, 18.5; 95% CI, 17.4-19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. Conclusions. cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk

Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case–control study of African Americans and whites

INTRODUCTION: A polymorphism in the manganese superoxide dismutase (MnSOD) gene, Ala-9Val, has been examined in association with breast cancer risk in several epidemiologic studies. Results suggest that the Ala allele increases the risk of breast cancer and modifies the effects of environmental exposures that produce oxidative damage to DNA. METHODS: We examined the role of the MnSOD Ala-9Val polymorphism in a population-based case–control study of invasive and in situ breast cancer in North Carolina. Genotypes were evaluated for 2025 cases (760 African Americans and 1265 whites) and for 1812 controls (677 African Americans and 1135 whites). RESULTS: The odds ratio for MnSOD Ala/Ala versus any MnSOD Val genotypes was not elevated in African Americans (odds ratio = 0.9, 95% confidence interval = 0.7–1.2) or in whites (odds ratio = 1.0, 95% confidence interval = 0.8–1.2). Greater than additive joint effects were observed for the Ala/Ala genotype and smoking, radiation to the chest, and occupational exposure to ionizing radiation. Antagonism was observed between the Ala/Ala genotype and the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The MnSOD genotype may contribute to an increased risk of breast cancer in the presence of specific environmental exposures. These results provide further evidence for the importance of reactive oxygen species and of oxidative DNA damage in the etiology of breast cancer

Prevalence of and risk for gastrointestinal bleeding and peptic ulcerative disorders in a cohort of HIV patients from a U.S. healthcare claims database.

The primary study objectives were to estimate the frequencies and rates of gastrointestinal bleeding and peptic ulcerative disorder in HIV-positive patients compared with age- and sex-matched HIV-negative subjects. Data from a US insurance claims database was used for this analysis. Among 89,207 patients with HIV, 9.0% had a GI bleed, 1.0% had an upper gastrointestinal bleed, 5.6% had a lower gastrointestinal bleed, 1.9% had a peptic ulcerative disorder diagnosis, and 0.6% had both gastrointestinal/peptic ulcerative disorder. Among 267,615 HIV-negative subjects, the respective frequencies were 6.9%, 0.6%, 4.3%, 1.4%, and 0.4% (p<0.0001 for each diagnosis subcategory). After combining effect measure modifiers into comedication and comorbidity strata, gastrointestinal bleeding hazard ratios (HRs) were higher for HIV-positive patients without comedication/comorbidity, and those with comedication alone (HR, 2.73; 95% confidence interval [CI], 2.62-2.84; HR, 1.59; 95% CI, 1.47-1.71). The rate of peptic ulcerative disorder among those without a history of ulcers and no comorbidity/comedication was also elevated (HR, 2.72; 95% CI, 2.48-2.99). Hazard ratios of gastrointestinal bleeding, and peptic ulcerative disorder without a history of ulcers were lower among patients infected with HIV with comedication/comorbidity (HR, 0.64; 95% CI, 0.56-0.73; HR, 0.46; 95% CI, 0.33-0.65). Rates of gastrointestinal bleeding plus peptic ulcerative disorder followed a similar pattern. In summary, the rates of gastrointestinal/peptic ulcerative disorder events comparing HIV-infected subjects to non-HIV-infected subjects were differential based on comorbidity and comedication status

Cutoff doses (mg/day) for NA-NSAIDs and aspirin (≤ low-dose or >high-dose).

<p>Cutoff doses (mg/day) for NA-NSAIDs and aspirin (≤ low-dose or >high-dose).</p

Univariate associations of effect measure modifiers utilized in hazard rate models.

<p>Univariate associations of effect measure modifiers utilized in hazard rate models.</p

Demographic and baseline characteristics of age- and sex-matched HIV-positive and HIV-negative patients.

<p>Demographic and baseline characteristics of age- and sex-matched HIV-positive and HIV-negative patients.</p

Conditional cox proportional-hazard models of HIV infection status and GI bleeding, PUD, or GI bleeding and PUD Events; stratified by effect measure modification using composite comorbidities and comedications determined individually for each of the 3 outcomes.

<p>Conditional cox proportional-hazard models of HIV infection status and GI bleeding, PUD, or GI bleeding and PUD Events; stratified by effect measure modification using composite comorbidities and comedications determined individually for each of the 3 outcomes.</p