Summary Background More than 1000 reports have been published in the past two decades on associations between variants in candidate genes and risk of breast cancer. Results have been generally ...inconsistent. We did a literature search and meta-analyses to provide a synopsis of the current understanding of the genetic architecture of breast-cancer risk. Methods A systematic literature search for candidate-gene association studies of breast-cancer risk was done in two stages, using PubMed on or before Feb 28, 2010. A total of 24 500 publications were identified, of which 1059 were deemed eligible for inclusion. Meta-analyses were done for 279 genetic variants in 128 candidate genes or chromosomal loci that had at least three data sources. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast-cancer risk. Findings 51 variants in 40 genes showed significant associations with breast-cancer risk. Cumulative epidemiological evidence of an association was graded as strong for ten variants in six genes ( ATM, CASP8, CHEK2, CTLA4, NBN , and TP53 ), moderate for four variants in four genes ( ATM, CYP19A1, TERT , and XRCC3 ), and weak for 37 variants. Additionally, in meta-analyses that included a minimum of 10 000 cases and 10 000 controls, convincing evidence of no association with breast-cancer risk was identified for 45 variants in 37 genes. Interpretation Whereas most genetic variants assessed in previous candidate-gene studies showed no association with breast-cancer risk in meta-analyses, 14 variants in nine genes had moderate to strong evidence for an association. Further evaluation of these variants is warranted. Funding US National Cancer Institute.
Black women diagnosed with epithelial ovarian cancer have poorer survival compared to white women. Factors that contribute to this disparity, aside from socioeconomic status and guideline‐adherent ...treatment, have not yet been clearly identified. We examined data from the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium which harmonized data on 1074 Black women and 3263 white women with ovarian cancer from seven US studies. We selected potential mediators and confounders by examining associations between each variable with race and survival. We then conducted a sequential mediation analysis using an imputation method to estimate total, direct, and indirect effects of race on ovarian cancer survival. Black women had worse survival than white women (HR = 1.30; 95% CI 1.16‐1.47) during study follow‐up; 67.9% of Black women and 69.8% of white women died. In our final model, mediators of this disparity include college education, nulliparity, smoking status, body mass index, diabetes, diabetes/race interaction, postmenopausal hormone (PMH) therapy duration, PMH duration/race interaction, PMH duration/age interaction, histotype, and stage. These mediators explained 48.8% (SE = 12.1%) of the overall disparity; histotype/stage and PMH duration accounted for the largest fraction. In summary, nearly half of the disparity in ovarian cancer survival between Black and white women in the OCWAA consortium is explained by education, lifestyle factors, diabetes, PMH use, and tumor characteristics. Our findings suggest that several potentially modifiable factors play a role. Further research to uncover additional mediators, incorporate data on social determinants of health, and identify potential avenues of intervention to reduce this disparity is urgently needed.
What's new?
Disparities in ovarian cancer survival between Black women and white women are accounted for in part by differences in socioeconomic status and adherence to treatment guidelines. The extent to which other factors, such as lifestyle, hormone therapy, and diabetes, influence these survival disparities remains unclear. In our study, using a novel statistical approach, the authors show that almost half of the disparity in ovarian cancer survival between Black women and white women is associated with lifestyle, education, diabetes, postmenopausal hormone use, and tumor characteristics. Further characterization of these mediating factors is essential to reducing racial disparities in ovarian cancer survival.
Diagnosed before age 50, early onset pancreatic malignancy (EOPM), is hypothesized to be a distinct subset of disease, although research is limited. To better characterize EOPM, and the effect of age ...at diagnosis on pancreatic cancer survival, we examined clinical characteristics and survival in EOPM and typical age‐at‐onset pancreatic malignancy (TOPM) cases. Vanderbilt University Medical Center (VUMC) Cancer Registry confirmed pancreatic adenocarcinomas (PDACs) and malignant pancreatic neuroendocrine tumors (PNETs) were evaluated. Clinical characteristics were compared using χ2 tests. Overall survival was visualized with Kaplan–Meier functions; Cox proportional hazards regression was used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 1,697 pancreatic malignancies were diagnosed at the VUMC between 1988 and 2013. Of 1,407 PDACs, 118 (8.4%) were EOPM, which was associated with significantly better survival (adjusted HR: 0.82, 95% CI: 0.67–1.00). EOPM and TOPM PDACs significantly differed with regard to having multiple malignancies; survival associations significantly differed by race, stage of disease, treatment and multiple malignancies. Of 190 PNETs, 63 (33.1%) were EOPM, which was not significantly associated with survival (adjusted HR: 0.80, 95% CI: 0.46–1.40). Malignant neuroendocrine EOPM and TOPM cases significantly differed by stage of disease and tumor location; survival associations significantly differed by family history of pancreatic cancer, stage of disease and multiple malignancies. Differences in clinical characteristics and associations with survival were identified, indicating that EOPM is distinct from TOPM, and exists among both pancreatic adenocarcinomas and malignant pancreatic neuroendocrine tumors.
What's new?
Pancreatic cancer that occurs before age 50 has not been well characterized. In this study, the authors compared survival and clinical characteristics in early‐onset vs. typical age‐at‐onset pancreatic cancers. They found that in pancreatic adenocarcinoma (PDAC), early onset confers significant survival advantage. This and differences in clinical characteristics for both PDACs and malignant pancreatic neuroendocrine tumors (PNETs) support the hypothesis that early onset pancreatic malignancy (EOPM) is a distinct subset of pancreatic cancers.
Family history (FH) of ovarian cancer and breast cancer are well‐established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women ...by histotype. We assessed first‐ and second‐degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race‐specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high‐grade serous vs others). First‐degree FH of ovarian cancer was associated with high‐grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First‐degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high‐grade serous carcinoma only in white women. Associations with second‐degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high‐grade serous carcinoma in both groups. First‐degree FH of ovarian cancer and of breast cancer, and second‐degree FH of ovarian cancer is strongly associated with high‐grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high‐grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.
What's new
Family history of breast or ovarian cancer are well known risk factors for ovarian cancer. Here, the authors looked at first‐ and second‐degree family history as it related to risk of epithelial ovarian cancer, stratified by serotype, among white and African American women. Having a first‐degree relative with breast cancer increased the risk in African American women regardless of histotype, but the increased risk was specific to high‐grade serous carcinoma (HGSC) in white women. First‐ or second‐degree history of ovarian cancer was associated with increased risk of high‐grade serous carcinoma in both racial groups, but less strongly associated with non‐HGSC.
We developed a decision analysis model to evaluate risks and benefits of delaying scheduled bariatric surgery during the novel coronavirus disease (COVID-19) pandemic. Our base case was a 45-year-old ...female with diabetes and a body mass index of 45 kg/m
2
. We compared immediate with delayed surgery after 6 months to allow for COVID-19 prevalence to decrease. We found that immediate and delayed bariatric surgeries after 6 months resulted in similar 20-year overall survival. When the probability of COVID-19 infection exceeded 4%, then delayed surgery improved survival. If future COVID-19 infection rates were at least half those in the immediate scenario, then immediate surgery was favored and local infection rates had to exceed 9% before surgical delay improved survival. Surgeons should consider local disease prevalence and patient comorbidities associated with increased mortality before resuming bariatric surgery programs.
Oral contraceptive use is associated with reduced ovarian cancer risk; however, associations with other contraceptive methods, such as intrauterine device (IUD) and tubal ligation, are less clear. ...Women in China differ from western women in regard to mechanisms and duration of use of contraception. This study was undertaken to evaluate associations between contraceptive methods and ovarian cancer risk using data from the prospective Shanghai Women's Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. A total of 174 epithelial ovarian cancer cases were found to occur among 70,259 women who were followed‐up for a total of 888,258 person‐years. The majority of women had ever used any contraception (77.0%), including IUD (55.6%), oral contraceptive (20.4%), tubal ligation (14.7%) or contraceptive shots (2.6%). Ever use of any contraception was associated with a nonsignificant reduction in ovarian cancer risk (HR: 0.86, 95% CI: 0.60–1.24). Longer duration of IUD use was associated with lower ovarian cancer risk (p‐value for trend = 0.04). Compared with never users, women with durations of IUD use longer than the median (20 years) were 38% less likely to develop ovarian cancer (HR: 0.62, 95% CI: 0.40–0.97). Based on the high prevalence and long duration of IUD use among Chinese women, we estimate a preventive fraction of 9.3%, corresponding to approximately 16 ovarian cancer cases. High prevalence of long‐term IUD use may, therefore, contribute to the low incidence of ovarian cancer observed in China.
What's new?
Patterns of contraceptive use are unique in China, where long‐term use of intrauterine devices (IUDs) is common. But the impact of that trend on ovarian cancer risk remains unclear. In this study, 55.6% of women in the Shanghai Women's Health Study reported ever‐use of IUD contraception, whereas oral contraceptive use was 20.4% and tubal ligation was 14.7%. While ever‐use of any contraception had little impact on ovarian cancer risk, IUD use for more than 20 years significantly reduced risk for the disease. The high prevalence of IUD contraception may be related to China's low incidence of ovarian cancer.
Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests ...that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from
,
, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.
Purpose
To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC).
Methods
We conducted a pooled case-only analysis of 1,793 ...Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2 + (HER2 +) and triple negative BC (TNBC) subtype relative to hormone receptor (HR) + /HER2- status (referent).
Results
Among 359 premenopausal women, 55.4% of cases were HR + /HER2 −, 20.1% were HER2 + , and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately, 50–60% of both pre- and postmenopausal women were obese (BMI > 30 kg/m
2
), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35 + kg/m
2
) was not associated with the development of HER2 + BC (OR 0.69; 95% CI 0.42–1.14) or TNBC (OR 0.93; 95% CI 0.60–1.45) relative to HR + /HER2- tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43–2.48) and 1.13 (95% CI 0.48–2.64).
Conclusion
In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.
While there is clear evidence for an association between later age at first live birth and increased breast cancer risk, associations with the timing of other reproductive events are less clear. As ...breast tissues undergo major structural and cellular changes during pregnancy, we examined associations between reproductive time events and intervals with breast cancer risk among parous women from the population‐based Shanghai Breast Cancer Study (SBCS). Unconditional logistic regression was used to evaluate associations with breast cancer risk for 3,269 cases and 3,341 controls. In addition to later age at first live birth, later ages at first pregnancy and last pregnancy were significantly associated with increased breast cancer risk (p‐trend = 0.002, 0.015, 0.008, respectively); longer intervals from menarche to first or last live birth were also associated with increased risk (p‐trend < 0.001, =0.018, respectively). Analyses stratified by menopausal status and estrogen receptor (ER)/progesterone receptor (PR) status revealed that associations for later age at first pregnancy or live birth and longer intervals from menarche to first or last live birth occurred among premenopausal women and ER+/PR+ breast cancers, whereas the association for later age at last pregnancy occurred among postmenopausal women and women with ER+/PR− or ER−/PR+ breast cancers. Because of the high correlation with other reproductive variables, models did not include adjustment for age at first live birth; when included, the significance of all associations was attenuated. These findings suggest that while reproductive time events and intervals play an important role in breast cancer etiology, contributions may differ by menopausal status and hormone receptor status of breast cancers.
What's new?
Early age at menarche and first live birth have been reported to be associated with decreased breast cancer risk by numerous studies; however, associations of other reproductive events and intervals is less clear, especially among Asian women. This large population‐based case‐control study is the first to comprehensively examine associations of reproductive time events and intervals with breast cancer risk among parous women, and is one of only a few such studies among Chinese women. Findings include that in addition to later age at first live birth, later age at first pregnancy, later age at last pregnancy, and longer intervals from menarche to either first live birth or last live birth were associated with increased breast cancer risk. Further, these associations were found to vary by menopausal status and hormone‐receptor status. Notably, the significance of all associations was attenuated when adjusted included age at first birth, possibly due to its high correlation with other reproductive events and intervals.
Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian ...cancer survival is limited.
We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis.
ABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60-0.93) or all non-A (HR: 0.77, 95% CI: 0.63-0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25-0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39-0.99) in unadjusted models.
Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.
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