In contrast to the unopposed estrogen used for some time as hormone replacement therapy (HRT) in the United States, combination regimens (CHRT) are becoming increasingly popular. With this approach, ...a progestin is added to estrogen for either the entire monthly cycle or sequentially. Because reassessment of the relationship between HRT and breast cancer seemed to be in order, a population-based, case-control study was planned. Women diagnosed with incident breast cancer in Los Angeles County were enrolled over a 4.5-year period starting in mid-1987. Cases included 1897 postmenopausal women ranging in age from 55 to 76 years; there were 1637 control women. No subject had undergone simple hysterectomy.HRT was used by 54 percent of breast cancer patients and 52 percent of control subjects. The average number of months of use was 46 and 43, respectively. A majority of users had received unopposed estrogen, most often relatively low doses (≤0.625 mg daily) of conjugated equine estrogen. CHRT was most often used sequentially; the progestin used was nearly always medroxyprogesterone acetate. The risk of breast cancer increased 10 percent for every 5 years of HRT use, for an odds ratio (OR) of 1.10. The findings suggested a steady rise in risk with an increasing duration of HRT use, to a level of 36 percent after 15 years of use. Estrogen replacement was not associated with the risk of breast cancer except in women using it for 15 years or longer (OR = 1.24). Thin women seemed to be more at risk than those who were heavy. The risk of breast cancer increased much more with the use of CHRT; the OR associated with 10 or more years of use was 1.51, and the estimated risk per 5 years of use was 1.24. Sequential CHRT carried a higher risk than a continuous regimen, but the difference was not statistically significant. With estrogen-only therapy, the excess risk was almost exclusively limited to in situ disease, but with CHRT, risk levels were comparable for all stages of cancer at presentation. The increased risk associated with CHRT was not restricted to current users; those who had stopped using this therapy 2 or more years earlier had a similar risk.These findings are evidence that adding a progestin to HRT substantially increases the risk of breast cancer compared with estrogen-only therapy. Women who are candidates for CHRT, in part to protect against endometrial cancer, should be aware that the increased risk of breast cancer may outweigh this benefit.J Natl Cancer Inst 2000;92:328–332
GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of ...inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10-4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.
Objective: Previous studies have suggested that high levels of galactose consumption and/or low levels of galactose-1-phosphate uridyl transferase (GALT) activity may result in an increased risk of ...epithelial ovarian cancer. Similarly, some have reported that carriers of the N314D (asparagine at codon 314 replaced by aspartate) GALT polymorphism, which can be associated with low GALT activity, may have a higher risk of ovarian cancer. We examined these issues as part of a large case-control study of ovarian cancer conducted in Los Angeles between 1992 and 1998. Methods: A total of 1439 histologically confirmed borderline and invasive ovarian cancer cases among English-speaking non-Asian women were ascertained through the population-based cancer registry for Los Angeles County and completed in-person interviews were obtained from 689 of these (78% of cases approached). Controls consisted of 645 English-speaking non-Asian women with at least one intact ovary matched to cases on race/ethnicity (African-American, Latina, non-Latina White), date of birth (±3 years), and neighborhood of residence. Interviewer-administered questionnaires included information on reproductive factors, exogenous hormone use, medical history, and diet. Dietary information for the year before each case's diagnosis (and the same period for her matched control) was obtained using a self-administered food-frequency questionnaire. Blood samples were obtained from 452 controls, 136 cases with borderline ovarian cancer, and 312 cases with invasive ovarian cancer. The N314D polymorphism was characterized using PCR-RFLP and GALT enzyme activity, and was determined for a sample of the subjects with GALT genotype using an erythrocyte-based radioactive enzyme assay. Results: We found no effect of N314D GALT genotype on the risk of borderline ovarian cancer (odds ratio (OR) = 0.91; 95% confidence interval (CI) = 0.54-1.6) or invasive ovarian cancer (OR = 0.78; 95% CI = 0.53-1.2). Neither did we observe a relationship between GALT activity or lactose/galactose intake and risk of borderline or invasive ovarian cancer. Among N314D carriers, galactose consumption was associated with an increased risk of borderline (OR = 2.7, p = 0.01), but not invasive (OR = 1.2, p = 0.34), ovarian cancer; however, this result was based on only 24 N314D-positive borderline cases. Conclusions: Differences in galactose intake and GALT metabolism do not contribute significantly to the risk of ovarian cancer. There is some evidence that galactose intake may play a role in the development of borderline ovarian cancer among women who carry the uncommon GALT N314D polymorphism. More data are needed if this latter suggestion is to be definitively addressed.
BACKGROUND: Hormone replacement therapy (HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing ...practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy CCRT) or a part of the cycle (sequential estrogen plus progestin therapy SEPRT). Few data exist on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of developing breast cancer in a population-based, case-control study. METHODS: Case subjects included those with incident breast cancers diagnosed over 4½ years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided. RESULTS: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR5 = 1.10; 95% confidence interval CI = 1.02-1.18). Risk was substantially higher for CHRT use (OR5 = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR5= 1.06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR5 = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR5= 1.09; 95% CI = 0.88-1.35), but this difference was not statistically significant. Conclusions: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.
Response Pike, Malcolm C.; Peters, Ruth K.; Cozen, Wendy ...
JNCI : Journal of the National Cancer Institute,
01/1998, Letnik:
90, Številka:
2
Journal Article
Few data exist on the extent to which the differences in breast cancer risk between “racial-ethnic” groups in the United States
(US) are “explained” by differences in their distribution of risk ...factors. We have determined this for African-American (AA),
native Hawaiian (NH), Japanese-American (JA), Latina-US-born (L-US), Latina-non-US-born (L-NUS), and white (W) women using
prospective incidence data on 88,712 postmenopausal women recruited in 1993–1996. We identified 1,757 incident breast cancer
cases through 1999 among these women (1,116 cases after excluding women with a simple hysterectomy or missing risk factor
data). Data were available on seven “known” risk factors: ages at menarche and first birth; parity; age at and type of menopause;
weight; hormone replacement therapy use; and alcohol consumption. The relative risks (RRs) of breast cancer (with the RR in
Ws set to 1.0) for the groups were as follows: W = 1.0; AA = 0.78; NH = 1.33; JA = 0.99; L-US = 0.77; and L-NUS = 0.60. After
adjustment for the risk factors, the RRs were as follows: W = 1.0; AA = 0.98; NH = 1.65; JA = 1.11; L-US = 0.95; and L-NUSB
= 0.84. The slightly greater risk of the JAs compared with the Ws is in sharp contrast to the very low breast cancer rates
that were observed in “traditional” Japanese women and in early Japanese migrants. The adjusted RR of NHs is 65% greater than
that of Ws, and that of migrant Latinas is 16% lower than that of Ws. Elucidating the causes of the high rates in NHs is now
a major focus of our efforts.
Abstract Objective Internalized stigma can lead to pervasive negative effects among people with severe mental illness (SMI). Although prevalence of internalized stigma is high, there is a dearth of ...interventions and meanwhile a lack of evidence as to their effectiveness. This study aims at unraveling the existence of different therapeutic interventions and the effectiveness internalized stigma reduction in people with SMI via a systematic review and meta-analysis. Methods Five electronic databases were searched. Studies were included if they (1) involved community or hospital based interventions on internalized stigma, (2) included participants who were given a diagnosis of SMI > 50%, and (3) were empirical and quantitative in nature. Results Fourteen articles were selected for extensive review and five for meta-analysis. Nine studies showed significant decrease in internalized stigma and two showed sustainable effects. Meta-analysis showed that there was a small to moderate significant effect in therapeutic interventions ( SMD = − 0.43; p = 0.003). Among the intervention elements, four studies suggested a favorable effect of psychoeducation. Meta-analysis showed that there was small to moderate significant effect ( SMD = − 0.40; p = 0.001). Conclusion Most internalized stigma reduction programs appear to be effective. This systematic review cannot make any recommendation on which intervention is more effective although psychoeducation seems most promising. More Randomized Controlled Trials (RCT) on particular intervention components using standard outcome measures are recommended in future studies.
Patients with pulmonary large-cell carcinoma (LCC) have poor prognosis and limited treatment options. The identification of clinically actionable molecular alterations helps to guide personalized ...cancer treatment decisions.
A consecutive cohort of 789 resected NSCLC cases were reviewed. Fifty-nine NSCLC cases lacking morphologic differentiation, accounting for 7.5% of all resected NSCLCs, were identified and further characterized by immunohistochemistry according to the 2015 WHO lung tumor classification. Molecular alterations were investigated by multiple technologies including target capture sequencing, immunohistochemistry, and fluorescence in situ hybridizations.
Of 59 NSCLC cases lacking morphologic differentiation, 20 (33.9%) were reclassified as adenocarcinoma (LCC-AD), 14 (23.7%) as squamous cell carcinoma (LCC-SqCC), and 25 (42.4%) as LCC-Null. Approximately 92% of LCC-Null, 95% of LCC-AD, and 86% of LCC-SqCC harbored clinically relevant alterations. Alterations characteristic of adenocarcinoma (EGFR, KRAS, ALK receptor tyrosine kinase ALK, ROS1, and serine/threonine kinase 11 STK11) were detected in the LCC-AD subgroup but not in LCC-SqCC, whereas squamous-lineage alterations (phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha PIK3CA, SRY-box 2 SOX2, fibroblast growth factor receptor 1 FGFR1, and AKT1) were detected in the LCC-SqCC subgroup but not in the LCC-AD group. Although some LCC-Null tumors displayed a genetic profile similar to either adenocarcinoma or squamous-cell carcinoma, more than half of the LCC-Null group were completely devoid of recognizable lineage-specific genetic profiles. High programmed death ligand 1 expression and high frequency of cell cycle regulatory gene alterations were found in the LCC-Null group offering alternative options of targeted therapy.
This comprehensive molecular study provided further insight into the genetic architecture of LCC. The presence of clinically actionable alterations in a majority of the tumors allowed personalized treatment to emerge.
Virtual influencers have great potential to shape the audience's perception and motivate behavioral change. Drawing upon anthropomorphism theory and social identity theory, this paper examined the ...interaction effect of anthropomorphism and racial homophily of virtual influencers in shaping audiences' trust and subsequently pro‐environmental behaviors in low‐ and high‐cost contexts. Two online studies employing experimental materials generated by artificial intelligence were conducted. Study 1 revealed that high anthropomorphism (human‐like virtual influencers) and high racial homophily (local‐like virtual influencers) are more effective for eliciting trust in the context of low‐cost pro‐environmental behaviors. The findings also showed that low racial homophily (foreign‐like virtual influencers) would further weaken the trust level of a virtual influencer in low anthropomorphism (animate‐like virtual influencers). Study 2 aimed to replicate the findings from Study 1 in the context of high‐cost pro‐environmental behaviors. The findings showed that low racial homophily (foreign‐like virtual influencers) enhanced the trust in a high anthropomorphism (human‐like virtual influencers) virtual influencer. The moderated mediation analyses confirmed the hypothesized relationships in the proposed research model. This research advanced our understanding on the moderating role of racial homophily that serves as a cognitive shortcut for low‐cost and quick decisions. However, a low racial homophily (foreign‐like) virtual influencer would be more effective for high‐cost and symbolic pro‐environmental behaviors. These insights provide valuable guidance to businesses, marketers, and environmental advocates aiming to leverage virtual influencers for encouraging sustainability practices.
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