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Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis. [ABSTRACT FROM AUTHOR]

The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case‐control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption. Pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none = 0.83; 95% CI = 0.58‐1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR = 0.44; 95% CI = 0.20‐0.97) and for invasive and borderline mucinous tumors combined (OR = 0.48; 95% CI = 0.26‐0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self‐reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample. [ABSTRACT FROM AUTHOR]

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. [ABSTRACT FROM AUTHOR]

Background:Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited.Methods:Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths).Results:Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)).Conclusions:Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted. [ABSTRACT FROM AUTHOR]

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC.Methods: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis.Results: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81).Conclusions: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence. [ABSTRACT FROM AUTHOR]

Objectives Animal evidence suggests that circadian disruption may be associated with ovarian cancer, though very little epidemiological work has been done to assess this potential association. We evaluated the association between self-reported nightshift work, a known circadian disruptor, and ovarian cancer in a population-based case-control study. Methods The study included 1101 women with invasive epithelial ovarian cancer, 389 women with borderline epithelial ovarian tumours and 1832 controls and was conducted in western Washington state. Shift work data were collected as part of inperson interviews. Results Working the nightshift was associated with an increased risk of invasive (OR=1.24, 95% CI 1.04 to 1.49) and borderline (OR=1.48, 95% CI 1.15 to 1.90) tumours; however, we observed little evidence that risks increased with increasing cumulative duration of nightshift work, and risks were not elevated in the highest duration category (>7 nightshift work-years). Increased risks were restricted to women who were 50 years of age and older and to serous and mucinous histologies of invasive and borderline tumours. There was suggestive evidence of a decreased risk of ovarian cancer among women reporting a preference for activity during evenings rather than mornings. Conclusions We found evidence suggesting an association between shift work and ovarian cancer. This observation should be followed up in future studies incorporating detailed assessments of diurnal preference (ie, chronotype) in addition to detailed data on shift schedules. [ABSTRACT FROM AUTHOR]

Purpose: Associations between sun exposure (a primary source of vitamin D) and risk of ovarian cancer have been inconsistent. Furthermore, studies have not investigated whether sun exposure at different periods in the lifetime of a person results in differences in risk associations, and little is known about differences according to histological subtype.Methods: Using a population-based case-control study of 1,334 non-Hispanic white women diagnosed with epithelial ovarian cancer in western Washington State between 2002 and 2009 and 1,679 non-Hispanic white controls, we assessed the relation of epithelial ovarian cancer with constitutional pigmentation characteristics, sun exposure behaviors, and an index of ultraviolet (UV) exposure based on residential history. Information was collected through in-person interviews. Logistic regression was used to compute odds ratios, 95 % confidence intervals, and trend p values (P(trend)).Results: We noted no association with residence-based measures of UV exposure or self-reported sun exposure, either over the lifetime or within specific age intervals. Also, we observed little evidence of association between constitutional pigmentation characteristics and risk, save for a suggestion of increased risk among women who reported increased ability to suntan upon prolonged sun exposure (P(trend) = 0.03).Conclusions: Results from this study suggest that sun exposure has little influence on the risk of epithelial ovarian cancer. Additional studies in populations with a wider gradient of sun exposure may yet be warranted. [ABSTRACT FROM AUTHOR]

Background: We conducted a population-based, case-control study to examine the association between the use of genital powder and ovarian cancer risk, including measures of extent and timing of exposure. We also assessed the relationship of powder use with risk of disease subtypes according to histology and degree of malignancy.Methods: Information was collected during in-person interviews with 812 women with epithelial ovarian cancer diagnosed in western Washington State from 2002 to 2005 and 1,313 controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: Overall, the perineal use of powder after bathing was associated with a slightly increased ovarian cancer risk (OR = 1.27, 95% CI: 0.97-1.66), which was most evident among women with borderline tumors (OR = 1.55, 95% CI: 1.02-2.37). We noted no clear pattern of risk increase on the basis of the extent of use, assessed as years in which powder was used, or as lifetime number of applications for invasive or borderline tumors, or their histologic subtypes. There was no alteration in the risk of ovarian cancer associated with other types of powder exposure (e.g., on sanitary napkins or diaphragms).Conclusions: The International Agency for Research on Cancer has designated perineal exposure to talc (via the application of genital powders) as a possible carcinogen in women. A modest association of ovarian cancer with this exposure was seen in our study and in some previous ones, but that association generally has not been consistent within or among studies. Therefore, no stronger adjective than "possible" appears warranted at this time. [ABSTRACT FROM AUTHOR]

Background: Physical activity may influence ovarian cancer risk through hormonal, inflammatory, or immune-mediated processes or by suppressing ovulation. In a population-based case-control study of epithelial ovarian cancer, we assessed risk associated with recreational physical activity with a focus on characterizing risk within histologic subtypes.Methods: Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002-2005 and 1,313 controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Exercise was assessed according to the average hours and metabolic equivalent (MET)-hours per week and the number of years in which regular recreational activity occurred.Results: Relative to women who reported no regular exercise throughout adulthood, the overall risk of invasive, but not borderline, ovarian cancer was reduced among more active women. Reductions in risk of invasive disease were most evident among women with the greatest frequency of high-intensity activity during adulthood. For serous invasive cancer, women in the uppermost category of MET-hours per week of recreational activity in adulthood had 60% the risk of inactive women (95% CI 0.4-0.9), whereas this level of activity was associated with more than a doubling in risk of endometrioid and clear cell invasive tumors.Conclusions: Our findings are compatible with an overall reduction in risk of invasive epithelial ovarian cancer associated with recreational activity but suggest that this association may differ in women with different histologic types of disease. Inconsistent findings across studies that have considered histologic type indicate that this issue is not yet resolved. [ABSTRACT FROM AUTHOR]

Background: A recent consensus statement encouraged use of certain symptoms to diagnose ovarian cancer earlier. We assessed the sensitivity, specificity, and positive predictive value of a proposed symptom index and of symptoms included in the consensus recommendation. [ABSTRACT FROM PUBLISHER]

The authors conducted a population-based case-control study of 410 women residing in three counties in western Washington State who were aged 18–64 years when diagnosed with papillary thyroid cancer in 1988–1994 and 574 controls to assess the effects of pregnancy history and other aspects of reproductive life on risk of this disease. Among women aged 45–64, the authors observed no associations with number of live births, age at first live birth, or age at last live birth. Risk was somewhat increased in women <45 years who had given birth within the previous 5 years; this association was most evident among women who reported that cancer symptoms had led to diagnosis. Among women who had given birth within the last 5 years, risk was greatest among those with two or more births during that time period (relative risk (RR) = 4.2, 95% confidence interval (Cl): 2.0, 8.9, relative to parous women whose last birth was >5 years before the reference date). Risk of thyroid cancer was also associated with lactation during the previous 5 years (e.g., RR = 2.9, 95% Cl: 1.5, 5.5, among parous women who had breastfed £12 months, vs. 0–1 months, during that interval). Our results suggest that thyroid stimulation during both pregnancy and lactation may result in a transient increase in risk of papillary thyroid cancer. Am J Epidemiol 2000;151:765–72. [ABSTRACT FROM PUBLISHER]

Objective: Some forms of ovarian neoplasms may be preventable through the removal of precursor lesions. We assessed the risk associated with a prior diagnosis of, and ovarian surgery following, ovarian cysts and endometriosis, with a focus on characterizing risk among tumor subgroups.Methods: Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002 to 2005 and 1,313 population-based controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: The risk of a borderline mucinous ovarian tumor associated with a history of an ovarian cyst was increased (OR=1.7, 95% CI: 1.0-2.8), but did not vary notably according to receipt of subsequent ovarian surgery. While risk of invasive epithelial ovarian cancer was slightly increased among women with a cyst who had no subsequent ovarian surgery, it was reduced when a cyst diagnosis was followed by surgery (OR = 0.6, 95% CI: 0.4-0.9). This reduction in risk was most evident for serous invasive tumors. Women with a history of endometriosis had a threefold increased risk of endometrioid and clear cell invasive tumors, with a lesser risk increase among women who underwent subsequent ovarian surgery.Conclusions: Our results suggest differences in the relation of ovarian cysts and endometriosis with risk of specific subtypes of ovarian cancer as well as the possibility that ovarian surgery in women with these conditions may lower the risk of invasive disease. [ABSTRACT FROM AUTHOR]

The authors conducted a population-based, case-control study among women aged 35–54 years to assess the influence of infertility and use of ovulation-inducing drugs on ovarian cancer risk. The study was conducted from 1994 to 1998 in three regions (metropolitan Atlanta, Georgia, Detroit, Michigan, and Seattle, Washington) and included 378 cases and 1,637 controls. Data were obtained through in-person interviews, and analysis was conducted using unconditional logistic regression. Among parous women, the authors observed no association of cancer risk with a history of infertility, medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Among nulliparous women, risk was increased among women with a history of infertility (odds ratio = 1.6, 95% confidence interval: 1.0, 2.6), particularly when infertility first became manifest relatively late in reproductive life (for first infertility at ≥30 years of age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.5); risk was not associated with medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Findings were similar when borderline and invasive epithelial tumors were considered separately. While the results of this study support the hypothesis that a subset of nulliparous women who experience infertility may be at increased risk of ovarian cancer, the reasons for this increase in risk remain unclear. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited.Methods: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths).Results: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)).Conclusions: Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted. [ABSTRACT FROM AUTHOR]