Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Breast-feeding and risk of epithelial ovarian cancer.

PURPOSE: Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail. METHODS: Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987). CONCLUSIONS: Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk.

We analyzed the polymorphic (CAG)n and (GGN)n regions within the androgen receptor gene from participants in a population-based case-control study of prostate cancer in middle-aged (40-64 years) Caucasian men. The associations between repeat lengths and risk of prostate cancer and the effects of confounding and modifying factors, such as age, family history of prostate cancer, and body mass index, were evaluated. DNA was available for 301 cases and 277 controls. The overall age-adjusted relative odds of prostate cancer associated with the number of (CAG) repeats as a continuous variable was 0.97 [95% confidence interval (CI), 0.92-1.03], suggesting a 3% decrease in risk of prostate cancer for each additional (CAG) repeat. Further analyses identified several subgroups at increased risk. These were men with less than the median number of CAG repeats (< 22) that were younger [< 60 years; relative odds (RO), 1.47; 95% CI, 0.96-2.25], had an affected first-degree relative (RO, 1.59; 95% CI, 0.62-4.14), or were relatively thin (Quetelet index < 24.4; RO, 2.21; 95% CI, 1.07-4.69). Although only the latter result was statistically significant, these results are provocative and support the hypothesis that (CAG)n array length is a predictor of risk for prostate cancer. Similar analyses of (GGN)n showed that with the exception of men with a family history of prostate cancer and those in the highest quartile of body mass index, men with < or = 16 repeats had higher risk estimates than did men with > 16 repeats. Overall, those men who had < or = 16 repeats had a significant elevation in risk (RO, 1.60; 95% CI, 1.07-2.41). When both repeat lengths were considered jointly, the subgroup with two short repeats (CAG, < 22; GGN, < or = 16) had a 2-fold elevation in odds (RO, 2.05; 95% CI, 1.09-3.84) relative to those with two long repeats (CAG, > or = 22; GGN, > 16). These data suggest that determination of both androgen receptor repeats within germ-line DNA may be useful in assessing an individual's risk of developing prostate cancer.

Vasectomy and risk of prostate cancer.

Most studies do not support an association between vasectomy and prostate cancer, but a few have suggested a link. Vasectomy is a common birth control method, and prostate cancer is the most frequently diagnosed solid tumor in men, making this a major public health question. This study was specifically designed to determine whether or not vasectomy is associated with risk of prostate cancer. To examine this issue, we conducted a population-based case-control study in King County, Washington. Interviews were completed with men ages 40-64 years newly diagnosed with prostate cancer between January 1993 and December 1996 who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry (n = 753) and with comparison men without prostate cancer identified from the same general population (n = 703). The odds ratio (OR) for prostate cancer in relation to vasectomy was assessed. The prevalence of vasectomy was similar in cases (39.4%) and controls (37.7%), resulting in no association (adjusted OR, 1.10; 95% confidence interval, 0.9-1.4). There was no consistent evidence that risk varied by the age at which vasectomy was performed, the time since vasectomy, or the calendar period when the vasectomy was performed. The OR in relation to vasectomy was higher in men with less aggressive prostate cancer. Risk estimates did not differ according to age, race, or family history of prostate cancer. This study suggests that vasectomy is not associated with the risk of developing prostate cancer. It also provides evidence that vasectomized men may be more likely to present with earlier-stage, lower-grade prostate tumors.

Sexual factors and the risk of prostate cancer.

A population-based case-control study of prostate cancer was performed in King County, Washington, in White men and Black men aged 40-64 years, between 1993 and 1996. Incident prostate cancer cases (n = 753) were identified from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Controls (n = 703) were identified through random digit dialing and were frequency matched to cases on age. Sexual behavior, medical history, and other potential prostate cancer risk factors were ascertained through an in-person interview. There was no relation between sexual orientation and prostate cancer, although the number of men who had sex with men was small. Risk estimates increased directly with the lifetime number of female sexual partners (trend p < 0.001) but not with male partners (trend p = 0.62). Risk also increased with decreasing age at first intercourse, but this effect disappeared after adjusting for the number of female partners. Prior infection with gonorrhea was positively associated with risk (odds ratio = 1.50; 95% confidence interval: 1.0, 2.2), but no effect was seen among men with other sexually transmitted diseases. No relation between lifetime frequency of sexual intercourse and risk of prostate cancer was apparent. These findings are consistent with previous studies that support an infectious etiology for prostate cancer.

Reproductive factors and risk of papillary thyroid cancer in women.

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 (CI): 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% CI: 1.5, 5.5, among parous women who had breastfed > or =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.

Respiratory cancer among orchardists in Washington State, 1968 to 1980.

A case-control investigation was conducted to evaluate the hypothesis that past exposure to the pesticide lead arsenate led to an excess mortality from respiratory cancer. Cases included all white male orchardists who died in Washington State between 1968 and 1980 from respiratory cancer. Orchardists who died of other causes during this period served as controls. Occupational and smoking data for 155 case subjects and 155 control subjects were obtained via telephone interview with next-of-kin/informants. Neither presence, intensity, nor duration of lead arsenate exposure differed between case and control subjects. Although cigarette smoking was unusually common among cases of respiratory cancer, smoking habits of the orchardists and a sample of non-orchardists who had died of other causes were quite similar. The cause of the excess mortality from respiratory cancer among Washington State orchardists remains unknown.

Use of exogenous hormones hormones and risk of papillary thyroid cancer (Washington, United States).

OBJECTIVES: Greater incidence of thyroid cancer in women than men, particularly evident during the reproductive years, has led to the suggestion that female hormones may increase risk of this disease. We conducted a population-based case-control study in women aged 18 to 64 years in three counties of western Washington State (United States) to assess the relation of use of exogenous hormones, including oral contraceptives (OC) and hormone replacement therapy (HRT), to risk of papillary thyroid cancer. METHODS: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988-94 who were identified as eligible, 468 (83.9 percent) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6 percent. Logistic regression was used to calculate odds ratios (OR) and associated 95 percent confidence intervals (CI) estimating the relative risk of papillary thyroid cancer among users of exogenous hormones. RESULTS: Among women aged 45 to 64 years, we observed no association of use of OCs or HRT with risk of papillary thyroid cancer. Among women less than 45 years of age, risk of papillary thyroid cancer was reduced in women who had ever used OCs (OR = 0.6, CI = 0.4-0.9); beyond the relation with ever-use, there was no further association with specific aspects of exposure such as estrogenic potency, latency, recency, age at first or last use, or use at the reference date. CONCLUSIONS: Our data do not support the hypothesis that use of exogenous estrogens increases the risk of female thyroid cancer.

Recreational physical activity and risk of papillary thyroid cancer (United States).

OBJECTIVE: Exercise has been hypothesized to influence cancer risk through a variety of mechanisms including hormonal, metabolic and immunologic effects, yet its relation with the risk of thyroid cancer has not been examined. We conducted a population-based case-control study in women aged 18-64 in three counties of western Washington State to assess the relation of recreational physical activity with risk of papillary thyroid cancer. METHODS: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988-1994 who were identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6%. Logistic regression was used to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with various aspects of recreational exercise. RESULTS: Risk of thyroid cancer was reduced among women who reported that they engaged in regular recreational exercise during the 2 years before diagnosis relative to women who did not report exercise during that time period (OR = 0.76, 95% CI 0.59-0.98). A similar risk reduction was noted among women who reported having exercised regularly between ages 12 and 21 (OR = 0.83, 95% CI 0.64-1.1). However, no clear associations with aspects of recreational activity, including average hours exercised per week or weekly energy expenditure, were observed. CONCLUSIONS: These results provide some initial support for the hypothesis that physical activity may reduce risk of thyroid cancer.

The association of fatty acids with prostate cancer risk.

BACKGROUND: Animal studies indicate that omega-6 fatty acids promote and omega-3 fatty acids inhibit tumor development. This pilot study was designed to evaluate whether these fatty acids are associated with human prostate cancer. METHODS: Levels of erythrocyte membrane omega-3 and omega-6 fatty acids were determined for 67 incident prostate cancer cases and 156 population-based controls. RESULTS: Prostate cancer risk was increased in the highest compared to the lowest quartile of alpha-linolenic acid (OR = 2.6, 95% CI = 1.1-5.8, trend P = 0.01). Positive associations were also observed with higher levels of linoleic acid (OR = 2.1, 95% CI = 0.9-4.8) and total omega-6 fatty acids (OR = 2.3, 95% CI = 1.0-5.4). CONCLUSIONS: Results are consistent with other studies showing that linoleic and total omega-6 fatty acids increase risk of prostate cancer. Contrary to animal studies, alpha-linolenic acid was also positively associated with risk. Further research will be required to clarify the role of these fatty acids in human prostate cancer.

Risk of papillary thyroid cancer in women in relation to smoking and alcohol consumption.

Both smoking and alcohol consumption may influence thyroid function, although the nature of these relations is not well understood. We examined the influence of tobacco and alcohol use on risk of papillary thyroid cancer in a population-based case-control study. Of 558 women with thyroid cancer diagnosed during 1988-1994 identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (N = 410). Controls (N = 574) were identified by random digit dialing, with a response proportion of 73.6%. We used logistic regression to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with cigarette smoking and alcohol consumption. A history of ever having smoked more than 100 cigarettes was associated with a reduced risk of disease (OR = 0.7, 95% CI = 0.5-0.9). This reduction in risk was most evident in current smokers (OR = 0.5, 95% CI = 0.4-0.7). Women who reported that they had ever consumed 12 or more alcohol-containing drinks within a year were also at reduced risk (OR 0.7, 95% CI = 0.5-1.0). Similar to the association noted with smoking, the reduction in risk was primarily present among current alcohol consumers. The associations we observed, if not due to chance, may be related to actions of cigarette smoking and alcohol consumption that reduce thyroid cell proliferation through effects on thyroid stimulating hormone, estrogen, or other mechanisms.

Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.

OBJECTIVE: To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest. DESIGN: Population-based case-control study. SETTING: Seattle and suburban King County, Washington. PARTICIPANTS: A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake. RESULTS: Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6). CONCLUSION: Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.

Diuretic therapy for hypertension and the risk of primary cardiac arrest.

BACKGROUND: The results of trials of the primary prevention of coronary heart disease have suggested that treating hypertension with high doses of thiazide diuretic drugs might increase the risk of sudden death from cardiac causes. In contrast, treatment with low doses of thiazide reduces the risk of coronary heart disease. METHODS: To examine the association between thiazide treatment for hypertension and the occurrence of primary cardiac arrest, we conducted a population-based case-control study among enrollees of a health maintenance organization. The case patients were 114 persons with hypertension who had a primary cardiac arrest from 1977 through 1990. The control patients were a stratified random sample of 535 persons with hypertension. The patients' treatment was assessed with the use of a computerized pharmacy data base. Records of their ambulatory care were reviewed to determine other clinical characteristics. RESULTS: The risk of primary cardiac arrest among patients receiving combined thiazide and potassium-sparing diuretic therapy was lower than that among patients treated with a thiazide without potassium-sparing therapy (odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). As compared with low-dose thiazide therapy (25 mg daily), moderate-dose therapy (50 mg daily) was associated with a moderate increase in risk (odds ratio, 1.7; 95 percent confidence interval, 0.7 to 4.5), and high-dose therapy (100 mg daily) was associated with a larger increase in risk (odds ratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (P value for trend, 0.02). The addition of a potassium-sparing drug to low-dose thiazide therapy was associated with a reduced risk of cardiac arrest (odds ratio, 0.4; 95 percent confidence interval, 0.1 to 1.5). CONCLUSIONS: Both the dose of thiazide drugs and the addition of potassium-sparing drugs influence the risk of primary cardiac arrest. These results may explain the differences in the effect of antihypertensive therapy on mortality from coronary heart disease in previous clinical trials.