Ovarian Cancer Incidence Rates Research Articles

Use of a Markov Model to Estimate Long-Term Insured Lives’ Mortality Risk Associated With BRCA1 and BRCA2 Gene Mutations

There is uncertainty regarding the degree of insurance risk associated with BRCA1/2, the gene mutations associated with breast cancer. Most reports to date have been based on high-risk populations selected from families with multiple and/or early-onset cancers; more favorable data have been reported in studies without this selection bias. This paper discusses use of a Markov model to estimate mortality risk associated with BRCA1/2 gene mutations in female life insurance applicants. The goal is to derive a range of risk estimates based on different assumptions of breast and ovarian cancer incidence. A particular strength of the model is that transition probabilities after cancer diagnosis vary with age and cancer stage, as do excess hazard rates. Data calculated by the model indicate that no single mortality curve characterizes risk for all life insurance applicants with a BRCA1/2 mutation. Rather, mortality risk depends on breast and ovarian cancer incidence rates and subsequent mortality rates, and on the method used to deal with competing breast and ovarian cancer incidence and mortality rates. Further refinement of risk estimates will depend on better incidence data and on resolution of complex statistical problems, such as informative censoring. Widespread use of genetic information by insurance consumers could have important economic implications. For companies that sell individually underwritten products, profitability might decrease. Consumers might find higher prices and reduced availability, with a corresponding decrease in quantity of insurance purchased. Insurance and consumer ramifications would vary by cover, with living-benefit products, such as critical-illness insurance, most adversely affected. Societal choices are limited. Given assumptions in the cited scenario, it is likely premiums would rise and quantity of insurance purchased would decrease even with no change in existing social policy; attempted legal or regulatory remedies would further accentuate price increases and reductions in quantity purchased.

Cross-sectionally derived hysterectomy prevalence for correcting uterine and ovarian cancer incidence rates and probabilities

PURPOSE: This paper presents a cross-sectional method for deriving age-specific hysterectomy prevalence. The influence of hysterectomy prevalence on uterine and ovarian cancer incidence rates and probabilities is illustrated.METHODS: Hysterectomy prevalence estimates are derived from cross-sectional data using a life table method. Analysis is based on hysterectomy data from the Utah Hospital Discharge Data Base and cancer cases recorded by the Utah Cancer Registry, 1995–1997.RESULTS: Correction for hysterectomy prevalence increases cancer incidence rates, more so at older ages, such that by ages 85 and older the increase is 92% for uterine cancers of the cervix and corpus, and 17% for ovarian cancer. Over the life span, correction for hysterectomy prevalence increases the estimated number per 100,000 developing these diseases by 195 (from 603 to 798) for uterine cervical cancer, 1,553 (from 2,580 to 4,133) for corpus uterine cancer, and 911 (1,674 to 2,585) for ovarian cancer.CONCLUSIONS: The utility of the cross-sectional method for deriving hysterectomy prevalence is that it does not require several years of data to obtain reasonable estimates. Correction for hysterectomy prevalence has a large effect on the cancer rates and probabilities, providing a more accurate representation of the risk and burden of these cancers.

Patterns in the incidence of age-related ovarian cancer in South East England 1967-1996.

To study the age-related trends in the incidence rates of ovarian cancer in South East England between 1967 and 1996. A retrospective review of systematically collected data on ovarian cancer in South East England. Data were obtained from the Thames Cancer Registry on the numbers and rates per 100,000 population of ovarian cancer per five-year age group (0-85+) in the 30-year period from 1967 to 1996 from the 26 health authorities in the Thames region. Linear regression was performed to determine the changes in incidence rates of ovarian cancer per age group over time. The change in overall incidence of ovarian cancer in South East England, as well as the change in incidence of ovarian cancer in each five-year age groups (20-85+) in the 30-year study period. There was a strong positive correlation between ovarian cancer rates and year of diagnosis in women aged > or = 70 years, and this was particularly marked in women > 85 years of age. There was a negative correlation between rates and year of diagnosis in women aged 45-59 years. The analysis did not demonstrate a significant correlation between ovarian cancer rates and year of diagnosis in women < 44 years of age or women aged 60-69 years. There have been significant changes in the pattern of ovarian cancer incidence in South East England during the 30-year period studied. The observed changes in ovarian cancer incidence in younger women may, in part, be explained by known reproductive factors. The rise in ovarian cancer rates among the older age group is difficult to explain, but has important implications for the future planning and provision of cancer services.

Declining ovarian cancer rates in U.S. women in relation to parity and oral contraceptive use.

Ovarian cancer incidence and mortality rates have declined among U.S. women age 35-59 years during the period 1970-1995. Epidemiologic studies have shown that ovarian cancer risk decreases with increasing parity and increasing duration of oral contraceptive use. During this period, parity has declined while oral contraceptive use has increased. We compared temporal trends in observed ovarian cancer incidence rates with rates predicted by changes in parity and duration of oral contraceptive use to determine whether the changes in these characteristics could explain the declining rates in younger women. In addition, we wished to examine whether oral contraceptive use continues to be protective to postmenopausal women. To predict changes in rates between 1970 and 1995, we assumed that increases in parity and duration of oral contraceptive use induce proportional decreases in incidence rates. We found that the rates predicted by these assumptions agreed well with observed rates in young women (age 30-49) but were substantially lower than observed rates in older women (age 50-64). The data indicate that the relative decrease in incidence rates due to the protective effect of oral contraceptive use declines with age.

Oral contraceptives and ovarian cancer.

The protection conveyed by oral contraceptives against ovarian cancer risk is one of the best established and most important features of epithelial ovarian cancer on a public health scale. Ovarian cancer incidence and mortality rates have been declining in most developed countries for women born after 1920, and the decline was greater in countries where oral contraceptive use has been more widespread. Thus, data from descriptive epidemiology are consistent with a favourable effect of oral contraceptives on ovarian cancer risks. The overall estimated protection from cohort and case-control studies is approximately 40% in ever oral contraceptive users, and increases with duration of use to more than 50% for users of 5 years or longer. The favourable effect of oral contraceptives against ovarian cancer risk persists for at least 10-15 years after use has ceased, and it is not confined to any particular type of oral contraceptive formulation. However, available data do not provide definite evidence for more recent low-dose formulations and for longer periods of latency or recency of use. The protection is also observed on borderline malignancy ovarian neoplasms, and probably on benign epithelial cysts as well. There is suggestive evidence of some protection for sex-cord-stromal cancers, but not for germ cell neoplasms. In terms of biological mechanisms, oral contraceptives are thought to act on ovarian cancer risk by affecting the lifetime number of ovulations. The protection attributable to oral contraceptives on ovarian cancer risk is one of the major issues on any individual risk/benefit assessment and public health evaluation of this type of contraceptive use.

Prognosis of patients with ovarian cancer and borderline tumours diagnosed in Norway between 1954 and 1993.

The Scandinavian countries exhibit some of the highest incidence rates of ovarian cancer in the world. Prognosis is poor, and the crude 5-year relative survival was 36% in the Nordic countries in the 1980s. Histology-specific prognostic trends in 5-year relative survival of patients with ovarian cancer and borderline tumours were examined, based on data from the population-based Cancer Registry of Norway. Relative risks (RRs) of dying were derived from Cox regression models. Logistic regression analysis on the proportion of cases with a localised tumour was performed. The 5-year relative survival rate of patients with ovarian cancer increased steadily from 1954 to 1993, being most pronounced in women below the age of 65 at the time of diagnosis. No improvement was seen for women older than 75. For all patients with ovarian cancer, an RR of dying of 0.48 (95% CI = 0.44-0.53) was estimated in 1989-1993 compared with 1954-1958. For patients with epithelial cancer, an RR of 0.63 (95% CI = 0.57-0.69) was seen in 1989-1993 compared with 1970-1973. Patients with mucinous, endometrioid and clear cell tumours had the highest odds of having a localised tumour. The age-adjusted 5-year relative survival rate of patients with borderline tumours was almost constant between 1970 and 1993, at about 93%. The prognosis of patients with ovarian cancer in Norway has improved since the 1950s. The very favourable prognosis of patients with borderline tumours has remained unchanged since the 1970s.

Incidence of ovarian cancer after hysterectomy: a nationwide controlled follow up.

To estimate the risk of developing ovarian cancer after abdominal (total or subtotal) hysterectomy on benign indication. Prospective historical cohort study with 12.5 years of follow up. Denmark, nationwide. All Danish women (aged 0 to 99 years) having undergone hysterectomy with conservation of at least one ovary for a benign indication from 1977 to 1981 (n = 22,135). Follow up was conducted from 1977 to 1991. The reference group included all Danish women who had not undergone hysterectomy, age-standardised according to the hysterectomy group (n = 2,554,872). Registry data derived from the Danish National Register of Patients (diagnoses and operation codes) and the Civil Registration System (information about general population, including time of death). Incidence rate of ovarian cancer, lifetime risk of ovarian cancer, relative risk of ovarian cancer. Seventy-one women developed ovarian cancer on average 7.0 years after hysterectomy and 10,659 women in the reference group had ovarian cancer diagnosed after on average 6.4 years. The incidence rate of ovarian cancer was 0.27 per 1000 person-years in the group that had undergone hysterectomy and 0.34 per 1000 person-years in the general population (age-standardised). The extrapolated lifetime risk of developing ovarian cancer was 2.1% after hysterectomy and 2.7% in the general population (RR 0.78; 95% CI 0.60-0.96). The risk of ovarian cancer is lower among women who have undergone hysterectomy compared with those who have not. The protection seems to decrease with time.

Ovarian Cancer

Ovarian cancer incidence rates are highest and stable in white populations; in Asia previously low incidence rates may be increasing. Most cases present with disseminated disease, and mortality rates remain high despite the use of aggressive polychemotherapy. Mortality among younger women has decreased, which has been attributed to widespread use of oral contraceptives. Studies consistently show a protective effect of oral contraceptives that increases with duration of use; no dose effect has been identified to date. Risk decreases substantially with increasing numbers of pregnancies; periods of lactation are relatively less protective. Periods of oral contraceptive use are less protective than equal periods of pregnancy. These factors may protect against ovarian cancer due to inhibition of ovulation or due to suppression of another aspect of ovarian function. Hysterectomy and tubal ligation are both protective, perhaps by preventing the ascent of environmental carcinogens that are as yet unidentified. A positive family history substantially increases risk; mutations in the BRCA1 gene may be responsible for about 5% of cases. No other exposures have been consistently associated with disease risk. Whether risk is modified by ovarian damage mediated by dietary galactose is being evaluated; studies to date have conflicting results. The effect of infertility and its treatments on ovarian cancer risk is controversial; two studies suggest that infertility treatments increase risk.

"The Estimated Effect of Oral Contraceptive Use on the Cumulative Risk of Epithelial Ovarian Cancer."

This study sought to determine the effect of oral contraceptive (OC) use on the cumulative incidence of epithelial ovarian cancer from ages 20 to 40 20 to 50m and 20 to 55 years among 4 groups of women: positive family history negative family history parous and nulliparous. Cancer and Steroid Hormone Study data were combined with data from the Surveillance Epidemiology and End Results Network to provide estimates of the age-specific incidence rates of epithelial ovarian cancer among never-users of OCs in the 4 specified groups of women. These rates provided the basis for calculating cumulative incidences. The rates in women using OCs were estimated from meta-analysis of the epidemiologic literature using regression equations expressing the log-relative rate of epithelial ovarian cancer as a function of duration of use and recency. In all 4 groups the cumulative number of epithelial ovarian cancer cases estimated to occur per 100000 OC users compared to never-users decreased with increasing duration of OC use. The authors results suggest that 5 years of OC use by nulliparous women can reduce their ovarian cancer risk to the level seen in parous women who never use OCs and that 10 years of OC use by women with a positive family history can reduce their risk to a level below that for women whose family history is negative and who never use OCs. These data represent the first published estimates of the effect of OC use on the cumulative incidence of epithelial ovarian cancer by family history and by parity. The demonstrated substantial noncontraceptive benefit from OCs justifies their judicious use as a potentially powerful resource for primary prevention in women at high risk of ovarian cancer. (authors)

Malignant and Benign Ovarian Neoplasms Among Atomic Bomb Survivors, Hiroshima and Nagasaki, 1950–80&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

For 1950-80, 194 ovarian cancer cases were ascertained among the 70,030 females of the Radiation Effects Research Foundation's Life-Span Study E-85 sample, and 106 autopsied cases with benign ovarian neoplasms were ascertained among all 3,046 autopsies performed in the same sample. On the basis of microscopic review, 66% of the cancer and 84% of the benign tumor cases were classified by histologic type. The age-adjusted ovarian cancer incidence rates showed a statistically significant increase with increased exposure dose, both in the entire exposed group (P less than .01) and in the microscopically reviewed subset (P less than .01). This dose response was only significant (P less than .01) in the latter half of the study period, 1965-80. The radiation effect was higher in the younger age group at the time of the bomb (ATB) for the specific attained age or was adjusted for attained age. In general, relative risk (greater than or equal to 100 rad vs. 0 rad) did not differ by attained age, except for the youngest age group, less than 20 years old ATB, where the relative risk tended to decrease with increased attained age, although cases were few in number and follow-up study was necessary. Estimated minimum latent period for radiation-induced ovarian cancer seemed to be 15-20 years. The proportion of autopsied cases with benign ovarian tumor increased with increasing exposure dose, both in the entire series of cases (P less than .05) and in the microscopically reviewed subset. Statistical significance, however, was not achieved in the latter group (P greater than .10). The distribution of histologic types of both cancer and benign tumor of the ovary did not vary significantly with radiation dose. The data are consistent with the hypothesis that radiation injury of the ovaries and secondary excess of gonadotropic hormones are important causative factors in the development of ovarian neoplasms.

Age-specific hysterectomy and oophorectomy prevalence rates and the risks for cancer of the reproductive system.

A sample survey was conducted in 1982 to determine the prevalence of hysterectomy and oophorectomy among upstate New York women, ages 25-74. The effects of this surgery on age-specific estimates of the risk for cancer of the uterus, cervix, and ovary were calculated. Overall, 16.9 per cent of the women reported having had a hysterectomy and 9.9 per cent reported a bilateral oophorectomy. The adjustment for age-specific hysterectomy increased the 1977-1979 average annual incidence rate of cervical and uterine cancer by 21 per cent. In several five-year age categories, the increase reached 54 per cent. The 1977-1979 average annual incidence rate of ovarian cancer increased by 12 per cent after adjusting for age-specific bilateral oophorectomy. The increase reached 29 per cent in one five-year age group. The sample results show a lower prevalence of hysterectomy among women 25 to 40 years old and among women 70 to 74 than estimates based on the application of mathematical models to data on surgical incidence.