09/17/2024


for more investigations on potential racial/ethnic differences in breast cancer biology. See related commentary by Wang et al., p. 704.
Metabolite profiles provide insight into biologic mechanisms contributing to breast cancer development. We explored the association between prediagnostic plasma metabolites (N = 307) and invasive breast cancer among postmenopausal women in a nested case-control study within the Nurses' Health Study (N = 1,531 matched pairs).

Plasma metabolites were profiled via LC/MS-MS using samples taken ≥10 years (distant, N = 939 cases) and <10 years (proximate, N = 592 cases) before diagnosis. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) comparing the 90th to 10th percentile of individual metabolite level, using the number of effective tests (NEF) to account for testing multiple correlated hypotheses. Associations of metabolite groups with breast cancer were evaluated using metabolite set enrichment analysis (MSEA) and weighted gene coexpression network analysis (WGCNA), with adjustment for the FDR.

No individual metabolites were significantly associated with breast cancer risk. MSEA showed negative enrichment of cholesteryl esters at the distant timepoint [normalized enrichment score (NES) = -2.26; Padj = 0.02]. Positive enrichment of triacylglycerols (TAG) with <3 double bonds was observed at both timepoints. TAGs with ≥3 double bonds were inversely associated with breast cancer at the proximate timepoint (NES = -2.91, Padj = 0.03).

Cholesteryl esters measured earlier in disease etiology were inversely associated with breast cancer. TAGs with many double bonds measured closer to diagnosis were inversely associated with breast cancer risk.

The discovered associations between metabolite subclasses and breast cancer risk can expand our understanding of biochemical processes involved in cancer etiology.
The discovered associations between metabolite subclasses and breast cancer risk can expand our understanding of biochemical processes involved in cancer etiology.
Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR(cg05575921) methylation improves specificity of lung cancer screening eligibility criteria.

A total of 9,206 and 5,370 individuals of the 1991 to 1994 and 2001 to 2003 examinations of the Copenhagen City Heart Study, Denmark, were followed for lung cancer within 5 years after examination and mortality. Screening eligibility criteria (DANTE, DLCST, ITALUNG, LUSI, NELSON, NLST, and PLCOM2012) were evaluated, and AHRR (cg05575921) methylation extent at different methylation cut points was added. The model with the lowest number of eligible individuals per 5-year lung cancer was validated within the 2001 to 2003 examination.

Eligibility criteria identified risk-groups ranging from 3,182 (DANTE) to 1,641 (ITALUNG) individuals. The positive predictive value was highest for PLCOM2012 (3.2%), while DANTE showed the highest negative predictive value (99.7%). Adding AHRR (cg05575921) methylationnal predictive risk information to identify eligible smokers for lung cancer screening. See related commentary by Hung, p. 698.
A social media campaign for mothers aimed at reducing indoor tanning (IT) by adolescent daughters reduced mothers' permissiveness toward IT in an immediate posttest. Whether the effects persisted at 6 months after the campaign remains to be determined.

Mothers (N = 869) of daughters ages 14-17 in 34 states without bans on IT by minors were enrolled in a randomized trial. All mothers received an adolescent health campaign over 12 months with posts on preventing IT (intervention) or prescription drug misuse (control). Mothers completed a follow-up at 18 months post-randomization measuring IT permissiveness, attitudes, intentions, communication, and behavior, and support for state bans. Daughters (n = 469; 54.0%) just completed baseline and follow-up surveys.

Structural equation modeling showed that intervention-group mothers were less permissive of IT by daughters [unstandardized coefficient, -0.17; 95% confidence interval (CI), -0.31 to -0.03], had greater self-efficacy to refuse daughter's IT requests (0.17; 95% CI, 0.06-0.29) and lower IT intentions themselves (-0.18; 95% CI, -0.35 to -0.01), and were more supportive of bans on IT by minors (0.23; 95% CI, 0.02-0.43) than control-group mothers. Intervention-group daughters expressed less positive IT attitudes than controls (-0.16; 95% CI, 0.31 to -0.01).

The social media campaign may have had a persisting effect of convincing mothers to withhold permission for daughters to indoor tan for 6 months after its conclusion. Reduced IT intentions and increased support for bans on IT by minors also persisted among mothers.

Social media may increase support among mothers to place more restrictions on IT by minors.
Social media may increase support among mothers to place more restrictions on IT by minors.
Epigenetic changes associated with human papillomavirus (HPV)-driven tumors have been described; however, HPV type-specific alterations are less well understood. We sought to compare HPV16-specific methylation changes with those in virus-unassociated head and neck squamous cell carcinomas (HNSCC).

Within The Cancer Genome Atlas, 59 HPV16+ HNSCC, 238 nonviral HNSCC (no detectable HPV or other viruses), and 50 normal head and neck tissues were evaluated. Significant differentially methylated regions (DMR) were selected, and key associated genes were identified. Partial least squares models were generated to predict HPV16 status in additional independent samples.

HPV infection in HNSCC is associated with type-specific methylomic profiles. Multiple significant DMRs were identified between HPV16+, nonviral, and normal samples. https://www.selleckchem.com/products/gant61.html The most significant differentially methylated genes, SYCP2, MSX2, HLTF, PITX2, and GRAMD4, demonstrated HPV16-associated methylation patterns with corresponding alterations in gene expression. Phylogenetically related HPV types (alpha-9 species; HPV31, HPV33, and HPV35) demonstrated a similar methylation profile to that of HPV16 but differed from those seen in other types, such as HPV18 and 45 (alpha-7).

HNSCC linked to HPV16 and types from the same alpha species are associated with a distinct methylation profile. This HPV16-associated methylation pattern is also detected in cervical cancer and testicular germ cell tumors. We present insights into both shared and unique methylation alterations associated with HPV16+ tumors and may have implications for understanding the clinical behavior of HPV-associated HNSCC.

HPV type-specific methylomic changes may contribute to understanding biologic mechanisms underlying differences in clinical behavior among different HPV+ and HPV- HNSCC.
HPV type-specific methylomic changes may contribute to understanding biologic mechanisms underlying differences in clinical behavior among different HPV+ and HPV- HNSCC.
Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC).

Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007-2015). Adherence [proportion of days covered (PDC) >80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions.

Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88-0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71-0.79).

Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk.

Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.
Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.
Financial hardship is most common among cancer survivors with the fewest financial resources at diagnosis; however, little is known about the financial outcomes of young adult (YA) survivors (ages 20-39 at diagnosis), despite their having fewer financial reserves than older adults.

We utilized data from 3,888 participants in the population-based Detroit Research on Cancer Survivors cohort. Participants self-reported several forms of material and behavioral financial hardship (MFH and BFH, respectively). Psychological financial hardship (PFH) was measured using the Comprehensive Score for financial Toxicity (COST) score. Modified Poisson models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for financial hardship by age at diagnosis controlling for demographic, socioeconomic, and cancer-related factors.

MFH prevalence was inversely associated with age such that 72% of YA survivors reported MFH, 62% ages 40 to 54, 49% ages 55 to 64, and 33% ages 65 to 79 (PRadjusted YA vs. 65+ 1.75; 95% CI, 1.49-2.04; Ptrend < 0.001). BFH was also more common among YA survivors (26%) than those ages 65 to 79 (20%; PRadjusted 1.50; 95% CI, 1.08-2.08; Ptrend = 0.019). Age was positively associated with financial wellbeing. COST scores ranged from 20.7 (95% CI, 19.0-22.4) among YA survivors to 27.2 (95% CI, 26.1-28.2) among adults 65 to 79 years old (Ptrend < 0.001).

In this population of African American cancer survivors, MFH and BFH were more common, and PFH was more severe, in YA survivors compared with those diagnosed as older adults.

Young adulthood at diagnosis should be considered a risk factor for cancer-related financial hardship and addressed in work designed to reduce the adverse financial impacts of cancer.
Young adulthood at diagnosis should be considered a risk factor for cancer-related financial hardship and addressed in work designed to reduce the adverse financial impacts of cancer.
Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes.

Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype.

During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype.

This study found no association between reproductive factors and survival after an ovarian cancer diagnosis.