Serous ovarian, fallopian tube and primary peritoneal cancers: a comparative epidemiological analysis

Invasive serous cancers are diagnosed in the ovary, fallopian tube and peritoneum. It is widely believed that these are variants of the same malignancy but little is known about fallopian tube and primary peritoneal cancers. A comparison of risk factors for these tumor types may shed light on common or distinct aetiological pathways involved in these types of cancer. We investigated risk factors for the three cancers using data from a large Australian population-based case-control study. We included women with incident invasive serous ovarian (n = 627), primary peritoneal (n = 129) and fallopian tube (n = 45) cancer and 1,508 control women. Participants completed a comprehensive reproductive and lifestyle questionnaire. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Hormonal contraceptive use was inversely related to risk of all three cancers. Parity and breast-feeding were also inversely related to risk of serous ovarian and fallopian tube cancer. In contrast, parous women had an increased risk of peritoneal cancer (OR = 1.8, 95%CI 0.8-3.9), and increasing parity did not lower risk. There was also no association between breast-feeding and peritoneal cancer. However, obesity was associated with a doubling of risk for peritoneal cancer alone (OR = 2.1, 95%CI = 1.3-3.4). The strikingly similar patterns of risk for serous ovarian and fallopian tube cancers and the somewhat different results for primary peritoneal cancer suggest that peritoneal cancers may develop along a different pathway. These results also call into question the role of the physical effects of ovulation in the development of serous ovarian cancer.     

Statin therapy and association with ovarian cancer risk in the New England Case Control (NEC) study

Statins are widely used to lower blood cholesterol and reduce risk for cardiovascular diseases, but attention has recently focused on a role in cancer prevention or therapy. Here we present data from a large case–control study addressing whether statin use can lower the risk for epithelial ovarian cancer (EOC). Between 1992 and 2008, data including medications used for at least 6 months were collected from 2,040 cases with EOC and 2,100 frequency-matched controls without the disease who participated in the New England Case Control study. We used unconditional logistic regression controlling for matching factors and potential confounders to examine the association between statin use and the risk for EOC. Overall, women who used statins had 32% lower risk of ovarian cancer compared to non-users (Odds ratio (OR) 0.68, 95% Confidence Interval (CI): 0.54–0.85), adjusting for the matching factors and other covariates. The reduced risk was most apparent in women taking a lipophilic statin who began use after age 49, and who had used them 2–4.9 years. Statin use was associated with lower risks for both serous and non-serous histologic subtypes with the strongest effect seen for mucinous and mixed epithelial subtypes. The association became apparent about a decade after the introduction of statins and did not appear to be confounded by indications for use of statins or medications used concomitantly. In this case–control study, statins were found to lower the risk for both serous and non-serous EOC and especially mucinous EOC.     

APOBEC3 deletion polymorphism is associated with epithelial ovarian cancer risk among Chinese women

Ovarian cancer remains the leading cause of death from gynecological malignancies and the second most common gynecological malignancy among women worldwide. However, the etiology still remains largely unknown. Previous studies identified APOBEC3 gene deletions were significantly associated with higher breast cancer risk in both European and Chinese women. Considering both breast and ovarian cancers being hormonally driven and sharing multiple risk factors, we performed this case–control study to evaluate the association between APOBEC3 deletion and epithelial ovarian cancer (EOC) risk. We analyzed the APOBEC3 deletion in a case–control study of 2,938 Chinese women (including 1,374 EOC cases and 1,564 healthy controls). All participants were genotyped using real-time qualitative PCR (qPCR). APOBEC3 deletion was significant associated with EOC risk, with ORs (95 % CIs) of 1.46 (1.14–1.86) associated with one copy deletion and 2.53 (0.91–7.06) associated with two copy deletion compared with subjects with no deletion (P for trend =1.50?×?10^?3). Additional adjustments and stratified analyses did not change the results materially. Our data suggests that the loss genotypes of APOBEC3 deletion predispose their carriers to EOC.     

Anti-Mullerian hormone and risk of invasive serous ovarian cancer

Purpose

Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer.

Methods

A case–control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986–2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations.

Results

Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49–1.77 for top vs. bottom tertile, P _trend = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49–0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06–2.54) was observed in younger women, P _homogeneity = 0.002.

Conclusions

In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.     

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.     

Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer

Coffee, alcohol and tobacco use have been examined in many epidemiologic studies of ovarian cancer but findings have generally been inconclusive. To explain prior inconsistent findings, we sought to determine whether associations with these exposures might vary by histologic subtype of ovarian cancer or menopausal status at diagnosis. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 549 women with newly-diagnosed epithelial ovarian cancer and 516 control women selected either by random digit dialing or through lists of residents. Coffee and alcohol consumption was assessed through a semi-quantitative food-frequency questionnaire, and information on tobacco smoking was collected through personal interview. Consumption of coffee and caffeine was associated with increased risk for ovarian cancer but only among premenopausal women. There was no increase in risk for ovarian cancer overall associated with tobacco or alcohol use in either pre- or post-menopausal women. Association of borderline significance for tobacco and invasive serous cancers and alcohol and mucinous cancers were observed but reduced after adjustment for coffee consumption. We conclude that coffee and caffeine consumption may increase risk for ovarian cancer among premenopausal women and are findings that have some epidemiologic and biologic support.     

Age at menarche and risk of ovarian cancer: A meta‐analysis of epidemiological studies

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta‐analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T‐T.G. and Q‐J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random‐effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta‐analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.     

Early pregnancy IGF‐I and placental GH and risk of epithelial ovarian cancer: A nested case‐control study

Insulin‐like growth factor‐I (IGF‐I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF‐I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF‐I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF‐I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975–2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF‐I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF‐I was associated with a nonsignificant decrease in risk for invasive [OR_{T3 vs. T1}: 0.79 (0.62–1.02); p_trend = 0.07] and endometrioid tumors [OR_{T3 vs. T1}: 0.55 (0.28–1.07); p_trend = 0.07]. The protective association between higher IGF‐I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [OR_{T3 vs. T1}: 0.74 (0.57–0.96); p_trend = 0.03]. Our study provides the first data on placental GH and IGF‐I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF‐I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.     

Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California

Perineal talc use has been suggested as a possible risk factor for ovarian cancer based on its structural similarity to asbestos, a known human carcinogen. A population-based epidemiologic case-control study of epithelial ovarian cancer (EOC) was conducted in 22 counties of Central California that comprise the reporting area for 2 regional cancer registries. Telephone interviews were conducted with 256 cases diagnosed in the years 2000-2001 and 1,122 controls frequency-matched on age and ethnicity. The interview obtained information on demographic factors, menstrual and reproductive experience, exogenous hormone use, surgical history and family history of cancer. Questions on perineal talc use included frequency of use, duration of use and specific years when talc was used. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression. The OR for ever use of talc was 1.37 (CI = 1.02-1.85) compared to never users. However, no dose response association was found. Tubal ligation (TL) modified the effect of talc on EOC such that women with TL had an OR of 0.88 (CI = 0.46-1.68) associated with perineal talc use, whereas women with no TL had an OR of 1.54 (CI = 1.10-2.16). Talc use and EOC risk was highest in women with serous invasive tumors (OR = 1.77; CI = 1.12-2.81). This study provides some support for the hypothesis that perineal talc use is associated with an increased risk of EOC.     

Lifetime recreational moderate-to-vigorous physical activity and ovarian cancer risk: A case–control study

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population-based case–control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age-periods in units of metabolic equivalents (METs)-hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change-in-estimate approach. The adjusted OR (95% CI) for each 28.5 MET-hr/week increment of lifetime recreational MVPA was 1.11 (0.99–1.24) for ovarian cancer overall. ORs for individual age-periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00–1.45) for those diagnosed before menopause and 1.04 (0.89–1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high-grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA.     

Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States)

Objective: A population-based case–control study was conducted to examine the hypothesis that active and passive tobacco smoking were associated with the risk of epithelial ovarian cancer. Methods: In-person interviews were obtained from 558 women with epithelial ovarian cancer (431 invasive, 127 borderline) and 607 population controls regarding active lifetime tobacco smoking, environmental tobacco smoke exposure in utero and during childhood, and other factors that may be related to the development of ovarian cancer. Results: No significant associations of ever or former tobacco smoking with the risk of invasive or borderline ovarian cancer were found, although long-term ex-smokers of 20 years or more were at significantly reduced risk of invasive cancer. Significant, positive dose–response relations of the number of cigarettes smoked per day and pack-years with the odds ratios for borderline cancer were evident. No association of active tobacco smoking with risk was found by histologic subtype of invasive ovarian cancer. Smokers were at significantly increased risk for borderline serous cystadenoma (OR: 1.91; 95% confidence intervals, CI: 1.09–3.34), but not for borderline mucinous cystadenoma. When we limited the analyses to current smokers, age-started smoking was significantly inversely related to the risk of invasive, but not borderline ovarian cancer. We found no association of gestational or childhood environmental tobacco smoke exposure with the risk of invasive or borderline ovarian cancer among never smokers. Conclusions: These findings do not support an association of active tobacco smoking with the risk of invasive ovarian cancer. An increased risk of borderline serous cystadenoma among smokers must be viewed with caution.     

Coffee, Tea and Caffeine and Risk of Epithelial Ovarian Cancer

OBJECTIVE: Studies evaluating the relationships between coffee, tea and caffeine and ovarian cancer risk have given inconsistent results. We have examined these associations using data from an Australian population-based case-control study. METHODS: Women with epithelial ovarian cancer (EOC) (n = 696) and control women selected from the Electoral Roll (n = 786) provided comprehensive reproductive and lifestyle data and completed a food frequency questionnaire. RESULTS: Increasing coffee consumption was associated with a decreased risk of invasive EOC ( p trend = 0.009) with an odds ratio (OR) of 0.51 (95% confidence interval (CI) 0.32-0.80) for consumption of >/=4 cups of coffee per day compared to non-drinkers. The association was significant only for serous and endometrioid/clear cell histological subtypes. There was no association with borderline tumours (OR: 1.20, 95% CI: 0.58-2.47). An inverse relationship was also seen between caffeine intake and EOC but tea consumption was not related to EOC (OR: 1.10 95% CI: 0.76-1.61 for >/=4 cups/day versus none). CONCLUSIONS: As tea contributed significantly to caffeine intake in this population we conclude that the association we observed with coffee is not due to caffeine, but to other components within coffee. We suggest future studies consider the type as well as the amount of each beverage consumed.     

Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary

Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype.     

A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer

Menopausal estrogen‐alone therapy (ET) is a well‐established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome‐wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case–control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non‐users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (p_int = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19–1.91), which was stronger for long‐term ET users of 10+ years (OR = 1.85, 95% CI 1.28–2.66, p_int = 0.034). Non‐users showed essentially no association (OR = 1.08, 95% CI 0.96–1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (p_int = 0.021 and p_int = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow‐up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci.     

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.     

Biology of epithelial ovarian cancer: implications for screening women at high genetic risk.

PURPOSE: Our aim was to analyze the clinicopathologic features of screen-detected ovarian cancers identified in women, either at general population risk or high genetic risk of ovarian cancer, who have participated in screening studies. METHODS: Studies published between 1988 and April 2003 were categorized by the population screened and the primary screening modalities used. Each report was examined with reference to the histologic type, stage, and grade of screen-detected cancers. Reports of studies of prophylactically removed ovaries from women at high risk of ovarian cancer were also reviewed. RESULTS: Of the stage I tumors detected by screening women at population risk, almost half were borderline ovarian tumors, granulosa-cell tumors, or germ-cell tumors, which is disproportionate to their frequency. Furthermore, of the stage I invasive epithelial cancers diagnosed in women at population risk, the majority were endometrioid, clear-cell, and mucinous histologic subtypes. Most ovarian cancers that occur in women at high genetic risk are high-grade serous cancers, and these are infrequently screen detected at an early stage. CONCLUSION: The clinicopathologic features of screen-detected ovarian cancers suggest that screening may not reduce mortality in women at increased genetic risk. Prospective screening studies are required in genetically high-risk populations to answer this important question. Women electing surveillance should be aware of the lack of proven benefit and the low likelihood of detecting early stage serous cancers. Bilateral salpingo-oophorectomy appears to be the most effective approach to decrease the risk of ovarian cancer and thereby reduce mortality in high-risk women.     

Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival

Use of hormone replacement therapy (HRT) has been hypothesized to affect survival of epithelial ovarian cancer (EOC). We studied 5-year survival in patients with invasive EOC and borderline ovarian tumors (BOT) according to HRT use before and after diagnosis in a prospective nation-wide cohort study of 799 women diagnosed with EOC (n = 649) and BOT (n = 150) aged 50-74 years in 1993-1995 in Sweden. Cox regression was used to obtain multivariate age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariate models included indicator variables for age, tumor stage, grade and histological subtype. After 5 years of follow-up, 45% of the patients with EOC and 93% of the patients with BOT were alive. For women with BOT there were no associations between HRT-use pre- or postdiagnosis and survival. There was no overall difference in 5-year EOC survival according to use HRT before diagnosis (multivariate HR = 0.83, 95% CI = 0.65-1.08), except for serous EOC (HR = 0.69, 95% CI = 0.48-0.98). Analyses of different HRT preparations, duration and recency of use did not reveal any variations in pattern of survival. We observed a better survival for EOC-patients who used HRT after diagnosis (multivariate HR = 0.57, 95% CI = 0.42-0.78). We conclude that HRT-use prior to diagnosis of EOC does not affect 5-year survival, except for a possible survival advantage in serous EOC. Women using HRT after diagnosis had a better survival than women with no use, but we cannot rule out that this latter finding may reflect a subtle selection process.     

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.     

Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations

Women from families with multiple cases of breast and ovarian cancer, specifically those who carry cancer-associated mutations of BRCA1or BRCA2are at increased life-time risk for peritoneal carcinoma, even after previous surgery to remove the ovaries, fallopian tubes and uterus. Hereditary breast–ovarian cancer (HBOC) syndrome and the associated BRCA1and BRCA2mutations are particularly prevalent in women of Jewish lineage, and specific BRCA1and BRCA2germline mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish populations, especially those of Ashkenazi descent. This review presents the currently available data and looks forward toward further and better understanding of peritoneal carcinoma in women with inherited susceptibility. Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1and BRCA2mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients. The best indications are that while many peritoneal carcinomas in genetically susceptible women may arise directly from malignant transformation of the peritoneum, others might represent metastases from primary ovarian or fallopian tube carcinomas. Although the incidence of borderline ovarian tumors may not be increased in HBOC syndrome kindreds and those who carry cancer-associated BRCA1and BRCA2mutations, these individuals could be susceptible to malignant transformation of borderline lesions of the ovaries and peritoneum. Moreover, recent reports raise the question of possibly increased risk in Jewish carriers of germline BRCA1mutations for uterine papillary serous carcinoma, which could be the source of metastasis to the peritoneum in some cases. The penetrance of cancer-associated BRCA1mutations for ovarian cancer is estimated to be 11%–54%, and for BRCA2mutations the penetrance for ovarian cancer is 11%–23%. So far, available screening methods appear to be insufficient for early detection of many ovarian cancers. Prophylactic oophorectomy has been found to reduce the risk for ovarian cancer in women from HBOC kindreds and those who carry cancer-associated BRCA1and BRCA2mutations, leaving a residual risk for peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of the ovaries, fallopian tubes and uterus, after child-bearing has been completed and by early in the fifth decade of life, are appropriate prophylactic procedures in women whose genetic susceptibility puts them at increased risk for cancers of mullerian tract origin, including ovarian and fallopian tube carcinomas and possibly serous carcinoma of the uterus. Hysterectomy, as well as salpingo-oophorectomy, removes the gynecologic organs targeted for malignant transformation in genetically susceptible women and simplifies decisions regarding hormone replacement therapy and chemical prophylaxis and treatment of breast cancer. Unless a transabdominal operative approach is otherwise indicated, laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and hysterectomy in women with hereditary susceptibility to gynecologic cancer.     

Circulating levels of insulin-like growth factor-I and risk of ovarian cancer

Insulin‐like growth factor (IGF)‐I, a mitogenic and anti‐apoptotic peptide, has been implicated in the development of several cancers. We hypothesized that high circulating IGF‐I concentrations may be associated with an increased risk of ovarian cancer. A case–control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). One hundred thirty‐two women with primary invasive epithelial ovarian cancer diagnosed at least 1 year after blood donation were case subjects. For each case, 2 control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. There was no association between IGF‐I concentrations and ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at a young age (<55), circulating IGF‐I was directly and strongly associated with ovarian cancer risk (OR = 4.97; 95% CI = 1.22–20.2 for the top vs. the bottom IGF‐I tertile after adjustment for parity, BMI categories and smoking). There was no significant association of IGF binding protein‐3 with ovarian cancer risk. We found a strong direct relationship between circulating IGF‐I levels and risk of developing ovarian cancer before age 55. Additional, larger studies of this association are needed to provide more precise estimates of effect. © 2002 Wiley‐Liss, Inc.