Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer

Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer.     

Benign Epithelial Ovarian Tumours—cancer Precursors or Markers for Ovarian Cancer Risk?

The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.     

HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: A proof of principle study

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age‐matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3‐fold by high HOXA9 methylation for all stages, and 14.8‐fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention. © 2009 UICC     

Hormone replacement therapy and risk of epithelial ovarian cancer.

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.     

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.     

Ovulation and risk of epithelial ovarian cancer

Incessant ovulation is thought to be one of the primary causes of epithelial ovarian cancer. However, the effects of ovulation at different ages and of the various exposures or events that suppress ovulation have not been established. We used data from an Australian case-control study of 791 ovarian cancer cases and 853 controls to examine the effect of ovulation on ovarian cancer risk. The total number of lifetime ovulations was calculated using information provided in a monthly contraceptive/reproductive calendar, as well as incorporating other information such as average menstrual cycle length. An increase of 1 year's worth of ovulation was associated with a 6% increase in risk of ovarian cancer (95% confidence interval [CI] = 4-8%). Ovulations in the 20-29-year age group were associated with the greatest risk, with a 20% increase in risk associated with each year of ovulation during this age period (95% CI = 13-26%). When the effects of different exposures that suppress ovulation were compared, there was an indication that some factors may have a greater effect than others. These findings support the theory that incessant ovulation is a major contributor to the occurrence of ovarian cancer and suggest that ovulations during the 20s may be those most associated with disease risk.     

A prospective study of dietary lactose and ovarian cancer

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.     

Alcohol consumption and ovarian cancer risk in a population-based case-control study

Alcohol consumption has been investigated as a possible risk factor for ovarian cancer in several epidemiological studies, with inconsistent findings. Recent studies have suggested that the association between alcohol consumption and ovarian cancer may vary according to histologic subtype of ovarian cancer and type of alcohol consumed (e.g., wine, beer, or liquor). We examined these associations in a population-based case-control study comprised of 762 incident cases of epithelial ovarian cancer and 6,271 population controls from Massachusetts and Wisconsin aged 40-79 years. Women reported their usual alcohol consumption as young adults (20-30 years of age) and in the recent past. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. There was no significant association of ovarian cancer with increasing alcohol consumption either during ages 20-30 years (p trend 0.42) or in the recent past (p trend 0.83). Regular drinking of beer (1 drink/day or more) during ages 20-30 (OR 1.55, 95% CI 1.07-2.26), though not liquor (OR 1.35, 95% CI 0.86-2.11) or wine (OR 0.99, 95% CI 0.49-2.00), was associated with a statistically significant increase in risk of invasive tumors, whereas no significant relationships were observed for recent drinking, regardless of alcohol type. The elevated risk for early adult regular drinking was confined to serous invasive tumors (OR 1.52, 95% CI 1.01-2.30), though results for other subtypes were based on sparse data and results were imprecise. In this study, neither total alcohol consumption as a young adult nor recently was associated with an increase in the risk of ovarian cancer.     

Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women's Health Study

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.     

Tibolone and risk of gynecological hormone sensitive cancer

Risk of ovarian cancer with hormone therapy is associated with use of both unopposed estrogen therapy and combined estrogen–progestin therapy, whereas for endometrial cancer addition of continuous progestin decreases the estrogen induced increased risk. Less is known about risk with use of tibolone; a synthetic steroid with estrogenic, progestagenic and androgenic properties. We assessed these associations in a prospective cohort study, including all Danish women 50–79 years of age and followed 1995–2009. National Danish Registers captured individually updated exposure information, cancer cases including histology and confounding factors. Poisson regression analyses provided multiple adjusted incidence rate ratios (IRRs). More than 900,000 women were followed for 9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with endometrial cancer. Compared to women never on postmenopausal hormone therapy, current users of tibolone had an increased IRR for ovarian cancer (1.42(95% confidence interval [CI], 1.01–2.00) and serous ovarian tumors (2.21(95%CI 1.48–3.32)). The risk increased with duration of use, particularly for serous ovarian tumors. Compared to never users, the IRR of endometrial cancer was 3.56(95%CI 2.94–4.32) among current users of tibolone and 3.80(95%CI 3.08–4.69) of Type I endometrial cancer. The steepest risk increase with duration of use was for Type I tumors. In conclusion, tibolone is associated with increased risk for ovarian and endometrial cancer overall; and particular the risk of serous ovarian tumors and Type I endometrial cancer. Because the associations are stronger with increasing durations of use – and for hormone sensitive tumors – the results seem indicative of causality.     

Tubal ligation,hysterectomy and epithelial ovarian cancer in the New England Case–Control Study

Previous studies have observed that tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer; however, little is known about whether these associations vary by surgical characteristics, individual characteristics or tumor histology. We used logistic regression to examine tubal ligation, simple hysterectomy and hysterectomy with unilateral oophorectomy in relation to risk of epithelial ovarian cancer in the New England Case–Control Study. Our primary analysis included 2,265 cases and 2,333 controls. Overall, tubal ligation was associated with a lower risk of epithelial ovarian cancer [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.68–0.97], especially for endometrioid tumors (OR = 0.45, 95% CI: 0.29–0.69). The inverse association between tubal ligation and ovarian cancer risk was stronger for women who had undergone the procedure at the time of last delivery (OR = 0.60, 95% CI: 0.42–0.84) rather than at a later time (OR = 0.93, 95% CI: 0.75–1.15). Overall, simple hysterectomy was not associated with ovarian cancer risk (OR: 1.09, 95% CI: 0.83–1.42), although it was associated with a nonsignificant decreased risk of ovarian cancer among women who underwent the procedure at age 45 or older (RR: 0.64, 95% CI: 0.40–1.02) or within the last 10 years (OR = 0.65, 95% CI: 0.38–1.13). Overall, women who had a hysterectomy with a unilateral oophorectomy had significantly lower risk of ovarian cancer (OR = 0.65, 95% CI: 0.45–0.94). In summary, tubal ligation and hysterectomy with unilateral oophorectomy were inversely associated with ovarian cancer risk in a large population‐based case–control study. Additional research is necessary to understand the potential biologic mechanisms by which these procedures may reduce ovarian cancer risk.     

Risk of ovarian cancer in the United States in relation to anthropometric measures: does the association depend on menopausal status?

Objective: To elucidate the association between anthropometric measures and ovarian cancer risk. Methods: From a population-based study of 563 cases of ovarian cancer and 523 controls we recorded weight, both at index age and age 18, and height using an in-person questionnaire, and used these to calculate body mass index (BMI). Multivariate logistic regression was used to calculate the exposure odds ratios, adjusted for established risk factors, stratified, in turn, by menopausal status and histologic type of ovarian cancer. Results: Height, weight, and BMI were unrelated to risk for ovarian cancer in the total group of cases and controls. After stratification by menopausal status, weight and BMI were associated positively with risk among premenopausal women, but did not affect risk postmenopausally. High BMI, weight, and height were most strongly related to risk of serous borderline cancer, particularly among premenopausal women. The association did not appear to be confined only to those overweight women with gynecologic problems such as irregular periods or ovarian cysts. Conclusions: Weight and BMI are positively related to premenopausal ovarian cancer risk in this population-based case–control study. This association is particularly noted for serous borderline tumors. This may suggest the importance of endocrine factors, which are altered in overweight women, such as insulin or androgens.     

BRCA2 Arg372Hispolymorphism and epithelial ovarian cancer risk

The BRCA2 372 HH genotype defined by the BRCA2 N372H nonconservative amino acid substitution polymorphism was recently reported to be associated with a small increased risk of breast cancer. We investigated whether this polymorphism was associated with ovarian cancer risk by conducting British and Australian case-control comparisons in parallel, including a total sample of 1,121 ovarian cancer cases and 2,643 controls. There was no difference in genotype frequency between control groups from the 2 studies (p = 0.9). The HH genotype was associated with an increased risk of ovarian cancer in both studies, and the risk estimate for the pooled studies was 1.36 (95% CI 1.04-1.77, p = 0.03). There was also a suggestion that this risk may be greater for ovarian cancers of the serous subtype for both studies, with an OR (95% CI) of 1.66 (1.17-2.54) for the 2 studies combined (p = 0.005). The BRCA2 372 HH genotype appears to be associated with an increased risk of ovarian cancer of a similar magnitude to that reported for breast cancer.     

Incomplete pregnancies and risk of ovarian cancer (Washington, United States)

Because of the reduced risk of ovarian cancer related to prior full-term pregnancies, we sought to determine whether there was any association with a history of one or more incomplete pregnancies. White female residents of three counties in Washington State (United States) diagnosed with ovarian cancer during 1986–88 (n=322), and a random sample of control women selected from these same counties (n=426), were interviewed regarding their pregnancy and childbearing histories. Among women who had given birth to at least one child, an additional incomplete pregnancy was not associated with the risk of ovarian cancer (relative risk [RR]=1.1, 95 percent confidence interval [CI]=0.8–1.6, adjusting for age, oral contraceptive use, and number of births). For those who had never given birth, a somewhat smaller proportion of cases had a history of incomplete pregnancy than controls (RR=0.8, CI=0.4–1.7). In an analysis restricted to ever-pregnant women, a prior induced or spontaneous abortion was not found to be associated with the incidence of ovarian tumors (RR=1.0, CI=0.6–1.7, and RR=1.3, CI=0.8–1.9, respectively). Other studies of the possible relation between incomplete pregnancies and ovarian cancer generally have observed either a weak negative association or no association at all. It is possible that if incomplete pregnancies do affect the risk of ovarian cancer, their impact might be too small to be identified reliably through epidemiologic studies.This research was supported in part by a grant from the US National Cancer Institute (R35 CA39779), and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-CN-05230 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center.     

Ovarian cancer risk in premenopausal and perimenopausal women treated with Tamoxifen: a case-control study

As tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increase ovarian cancer risk in women treated premenopausally. In a national case-control study in Britain, treatment histories were collected for 158 cases of ovarian cancer after breast cancer diagnosed at ages under 55 years and 464 controls who had breast cancer at these ages without subsequent ovarian cancer. Risk of ovarian cancer was not raised for women overall who had taken tamoxifen (odds ratio (OR)=0.9, 95% confidence interval (CI) 0.6-1.3) or for those treated when premenopausal (OR=1.0, 95% CI 0.6-1.6) or perimenopausal (OR=0.7, 95% CI 0.2-2.4). There was also no relation of risk to daily dose, duration or cumulative dose of tamoxifen, or time since last use. There was, however, a significantly raised risk in relation to non-hormonal chemotherapy. The results suggest that tamoxifen treatment of premenopausal or perimenopausal women does not materially affect ovarian cancer risk, but that non-hormonal chemotherapy might increase risk.     

Risk of epithelial ovarian tumors among women with polycystic ovary syndrome: A nationwide population-based cohort study

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted.     

Medication use and risk of ovarian carcinoma: a prospective study

Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study.     

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.     

Aspirin,other NSAIDs,and ovarian cancer risk (United States)

Objective: We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories. Methods: We prospectively assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses' Health Study who had no history of cancer other than non-melanoma skin cancer. Women reported known and suspected ovarian cancer risk factors in biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988–1994. We assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992, and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of invasive epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, body mass index, oral contraceptive use, smoking history, parity, postmenopausal hormone use, tubal ligation, and other potential ovarian cancer risk factors. Results: Aspirin use was not associated with ovarian cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence interval (CI 0.80–1.25). We found no association between aspirin dose (in number of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more tablets weekly compared with nonusers, 0.98, 95% CI 0.63–1.52). Similarly, duration of aspirin use was not associated with risk (RR for aspirin use of 20 or more years, 0.99, 95% CI 0.69–1.43). In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40% reduction in risk among NSAID users versus nonusers (RR 0.60, 95% CI 0.38–0.95). However, when we examined this relationship in terms of days of NSAID use per month, we did not observe a dose–response with increasing NSAID use. Conclusions: We observed no association between aspirin use, dose, or duration and epithelial ovarian cancer risk. Although we found a modest reduction in risk associated with NSAID use, there was no dose–effect.     

Body size and risk of epithelial ovarian and related cancers: a population-based case-control study

Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer.