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1.
Int J Cancer ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433939

RESUMO

When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well-studied. We pooled data from four large, prospective cohorts (the Nurses' Health Study, the Nurses' Health Study II, the Sister Study and the Women's Health Initiative - Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow-up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI: 0.94-1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI: 0.95-1.16; P-for-trend = .46). Long-term use (>20 years; HR = 1.12, 95% CI: 0.96-1.31; P-for-trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow-up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long-term use may merit further consideration.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33335022

RESUMO

BACKGROUND: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. METHODS: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. RESULTS: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679-0.721]). Our model had slightly improved discrimination (0.714 [0.694-0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. CONCLUSIONS: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. IMPACT: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.

3.
Eur J Epidemiol ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331993

RESUMO

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses' Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65-0.91]; >10 years of use, 0.43 [0.32-0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41-0.67]) and second-generation progestins (0.43 [0.30-0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50-0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49-0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.

4.
Eur J Epidemiol ; 35(11): 1025-1042, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32959149

RESUMO

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.

5.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732252

RESUMO

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

6.
Gynecol Oncol ; 158(3): 702-709, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32641237

RESUMO

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

7.
Cancer Epidemiol Biomarkers Prev ; 29(9): 1739-1749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32616494

RESUMO

BACKGROUND: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis. RESULTS: A positive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintileQ5-Q1 = 1.29; 95% confidence interval (CI) = 1.03-1.62; P trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P trend = 0.03) and n-3 α-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertileT3-T1 = 1.39; 95% CI = 0.99-1.94; P trend = 0.06) and α-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P trend = 0.06). CONCLUSIONS: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer. IMPACT: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.

8.
Clin Cancer Res ; 26(20): 5411-5423, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32554541

RESUMO

PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.

9.
JAMA Oncol ; 6(6): e200421, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239218

RESUMO

Importance: Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent. Objective: To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype. Design, Setting, and Participants: A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019. Exposures: Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies. Main Outcomes and Measures: Diagnosis of epithelial ovarian cancer. Results: A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02). Conclusions and Relevance: Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.

10.
Int J Cancer ; 147(8): 2042-2052, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32243586

RESUMO

A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.

11.
Int J Cancer ; 147(5): 1325-1333, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32011733

RESUMO

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2 ), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2 ) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.

12.
Breast Cancer Res ; 22(1): 23, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075687

RESUMO

BACKGROUND: Experimental and epidemiological studies demonstrate a role for 27-hydroxycholesterol (27HC) in breast cancer development, though results are conflicting. Cholesterol 27-hydroxylase (CYP27A1) and oxysterol 7-alpha-hydroxylase (CYP7B1) regulate 27HC concentrations, while differential expression of the liver X receptor (LXR) and estrogen receptor beta (ERß) may impact the association between 27HC and breast cancer risk. METHODS: We evaluated correlates of tumor tissue expression of CYP27A1, CYP7B1, LXR-ß, and ERß and the association between circulating prediagnostic 27HC concentrations and breast cancer risk by marker expression in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort including 287 breast cancer cases with tumor tissue available. Tumor protein expression was evaluated using immunohistochemistry, and serum 27HC concentrations quantified using liquid chromatography-mass spectrometry. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A higher proportion of CYP7B1-positive cases were progesterone receptor (PR)-positive, relative to CYP7B1-negative cases, whereas a higher proportion of ERß-positive cases were Bcl-2 low, relative to ERß-negative cases. No differences in tumor tissue marker positivity were observed by reproductive and lifestyle factors. We observed limited evidence of heterogeneity in associations between circulating 27HC and breast cancer risk by tumor tissue expression of CYP27A1, CYP7B1, LXR-ß, and ERß, with the exception of statistically significant heterogeneity by LXR-ß status in the subgroup of women perimenopausal at blood collection (p = 0.02). CONCLUSION: This exploratory study suggests limited associations between tumor marker status and epidemiologic or breast cancer characteristics. Furthermore, the association between circulating 27HC and breast cancer risk may not vary by tumor expression of CYP27A1, CYP7B1, LXR-ß, or ERß.


Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Hidroxicolesteróis/sangue , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Colestanotriol 26-Mono-Oxigenase/metabolismo , Família 7 do Citocromo P450/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Alemanha/epidemiologia , Humanos , Receptores X do Fígado/metabolismo , Pessoa de Meia-Idade , Tipagem Molecular/métodos , Gradação de Tumores , Avaliação Nutricional , Estudos Prospectivos , Fatores de Risco , Esteroide Hidroxilases/metabolismo
13.
Cancer Res ; 80(9): 1885-1892, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32075798

RESUMO

Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case-cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER- subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development. SIGNIFICANCE: This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals.See related commentary by Song and Tworoger, p. 1801.


Assuntos
Neoplasias , Linfócitos T Reguladores , Estudos de Coortes , Epigênese Genética , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
14.
Cancer Res ; 80(5): 1210-1218, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.


Assuntos
Neoplasias Ovarianas/epidemiologia , Ovário/imunologia , Ovulação/imunologia , Idoso , Anticoncepcionais/administração & dosagem , Tubas Uterinas/imunologia , Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Ovário/patologia , Ovulação/efeitos dos fármacos , Modelos de Riscos Proporcionais , Estudos Prospectivos , História Reprodutiva , Medição de Risco , Fatores de Risco
15.
Int J Cancer ; 146(12): 3267-3280, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31506954

RESUMO

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

16.
Eur J Nutr ; 59(7): 2929-2937, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31705265

RESUMO

PURPOSE: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. METHODS: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). RESULTS: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. CONCLUSIONS: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

17.
J Ovarian Res ; 12(1): 116, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771659

RESUMO

BACKGROUND: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. METHODS: We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. RESULT: The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. CONCLUSIONS: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.


Assuntos
Antígeno Ca-125/sangue , Detecção Precoce de Câncer , Modelos Teóricos , Neoplasias/diagnóstico , Pós-Menopausa/sangue , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/sangue
18.
BMC Med ; 17(1): 178, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31547832

RESUMO

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Metabolômica/métodos , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
19.
Cancer Res ; 79(20): 5442-5451, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31462430

RESUMO

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. SIGNIFICANCE: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Carcinoma/sangue , Proteínas de Neoplasias/sangue , Neoplasias Ovarianas/sangue , Idoso , Carcinogênese , Carcinoma/classificação , Carcinoma/epidemiologia , Estudos de Casos e Controles , Intervalos de Confiança , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Inflamação , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Ovarianas/epidemiologia , Estudos Prospectivos , Risco , Fatores de Risco , Sensibilidade e Especificidade , Estados Unidos/epidemiologia
20.
Int J Epidemiol ; 48(3): 807-816, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31143958

RESUMO

BACKGROUND: There are observational data suggesting an inverse association between circulating concentrations of sex hormone binding globulin (SHBG) and risk of postmenopausal breast cancer. However, causality is uncertain and few studies have investigated this association by tumour receptor status. We aimed to investigate these associations under the causal framework of Mendelian randomization (MR). METHODS: We used summary association estimates extracted from published genome-wide association study (GWAS) meta-analyses for SHBG and breast cancer, to perform two-sample MR analyses. Summary statistics were available for 122 977 overall breast cancer cases, of which 69 501 were estrogen receptor positive (ER+ve) and 21 468 were ER-ve, and 105 974 controls. To control for potential horizontal pleiotropy acting via body mass index (BMI), we performed multivariable inverse-variance weighted (IVW) MR as the main analysis, with the robustness of this approach further tested in sensitivity analyses. RESULTS: The multivariable IVW MR analysis indicated a lower risk of overall (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.90, 0.98; P: 0.006) and ER+ve (OR: 0.92; 95% CI: 0.87, 0.97; P: 0.003) breast cancer, and a higher risk of ER-ve disease (OR: 1.09; 95% CI: 1.00, 1.18; P: 0.047) per 25 nmol/L higher SHBG levels. Sensitivity analyses were consistent with the findings of the main analysis. CONCLUSIONS: We corroborated the previous literature evidence coming from observational studies for a potentially causal inverse association between SHBG concentrations and risk of ER+ve breast cancer, but our findings also suggested a potential novel positive association with ER-ve disease that warrants further investigation, given the low prior probability of being true.


Assuntos
Neoplasias da Mama/epidemiologia , Globulina de Ligação a Hormônio Sexual/metabolismo , Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Feminino , Humanos , Análise da Randomização Mendeliana , Razão de Chances , Receptores Estrogênicos/metabolismo , Globulina de Ligação a Hormônio Sexual/genética
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