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Diet and risk of seromucinous benign ovarian cysts
European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
Diet and risk of seromucinous benign ovarian cysts Francesca Chiaffarinoa, Fabio Parazzinia,b,*, Matteo Suracea, Guido Benzib, Vito Chianteraa, Carlo La Vecchiaa,c a
Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, via Eritrea, Milano 62-20157, Italy Clinica Ostetrico Ginecologica, Istituto Clinico di Perfezionamento, Universita` di Milano, Milano, Italy c Istituto di Statistica Medica e Biometria, Universita` degli Studi di Milano, Milano, Italy
b
Received 20 June 2002; received in revised form 20 January 2003; accepted 3 February 2003
Abstract Objective: To analyze the relation between selected dietary indicators and the risk of seromucinous benign ovarian cysts. Study design: We used data from a case–control study on risk factors for benign ovarian cysts conducted in Italy between 1984 and 1994. Cases included 225 women with a histologically confirmed diagnosis of benign seromucinous ovarian neoplasm dating back no more than 2 years. Controls were 450 women below the age of 65 years admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions. Results: Women with seromucinous cysts reported more frequent consumption of beef and other red meat and cheese and less frequent consumption of green vegetables. The multivariate odds ratios (ORs) in highest versus less frequent consumption levels were 2.7 (95% confidence interval (CI) 1.8–4.3) for beef and other red meat, 0.6 (95% CI 0.3–0.9) for green vegetables and 1.4 (95% CI 1.0–2.2) for cheese. Conclusion: Seromucinous benign ovarian cysts are associated with beef and cheese consumption, whereas high intake of green vegetables seems to have a protective effect. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Diet; Risk factors; Ovarian cysts
1. Introduction
2. Methods
Relatively little is known concerning the etiology of seromucinous ovarian cysts, although hormonal factors appear to be important. It is known that nutrition and diet are related to sex hormones and their binding proteins, and this provides a plausible biological explanation for a potential association between diet and seromucinous ovarian cysts [1,2]. A population-based study, of 668 cases and 347 controls analyzed, conducted in metropolitan area of New York, USA, has recently suggested that polyunsaturated and hence vegetable fat may increase the risk of benign ovarian tumors [3]. None of the others nutrients considered, included lactose intake [4] were related to benign ovarian tumors. Using data from a case–control study, conducted in northern Italy, we have considered the potential role of selected foods in the etiology of seromucinous ovarian cancer.
Between 1984 and 1994 we conducted a case–control study of benign ovarian cysts, whose design and methods has been previously described [5,6]. Briefly, cases included 225 women aged less than 65 years (median age 38 years; age range 15–64 years) with a histologically confirmed diagnosis of benign seromucinous ovarian neoplasm, admitted to a network of obstetrics and gynecology departments in Milan. The clinical diagnoses of cases dated back no more than 2 years. Controls were women below the age of 65 years admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions to the Ospedale Maggiore (including the four major teaching and general hospitals in Milan) and several university clinics, serving a catchment area comparable to that of the hospitals where cases had been identified. They were recruited within the framework of a case–control study of female genital neoplasm. Out of a total of 2654 subjects interviewed, 450 controls were identified (age range 16–64 years; median age 38 years), matched with cases in a 1:2 ratio, and randomly selected within strata of 5 years age groups and calendar years of interview. Of these, 34% were
* Corresponding author. Tel.: þ39-02-390141; fax: þ39-02-33200231. E-mail address: [email protected] (F. Parazzini).
0301-2115/$ – see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00115-5
F. Chiaffarino et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
admitted for traumatic conditions (mostly fractures and sprains), 26% had non-traumatic orthopedic disorders (mostly low back pain and disc disorders), 17% acute abdominal diseases requiring surgery, and 23% other miscellaneous illnesses, such as disorders of the ear, nose, throat, or teeth. Trained interviewers identified and questioned cases and controls. All interviews were conducted in hospital. Less than 3% of cases and controls refused to be interviewed. Information was obtained, using a structured questionnaire, on general sociodemographic factors, personal characteristics and habits, gynecological and obstetric history, and lifetime oral contraceptive use. Subjects were also asked about frequency of consumption per week of selected dietary items (including the major sources of retinoids and carotenoids in the Italian diet), such as milk, beef and other red meat, liver, carrots, green vegetables, fresh fruit, eggs, ham, fish, cheese, whole grain in the year before interview. Moreover, the intake of metilxantine (coffee, tea, cola) and of alcoholic beverage (wine, beer, spirits) were collect as number of cup or glasses/day, number of days/week and duration (years) of consumption. Subjective scores (low, intermediate and high) were used to collect information on fat intake (butter, margarine and oil) and consumption of whole grain foods. Reproducibility of the questionnaire was satisfactory [7,8]. The cut-off for the analysis of dietary factors were based on the best possible approximation of tertiles. An estimate of the total daily average alcohol intake was derived assuming a comparable ethanol content in each type of beverage (125 ml wine ¼ 333 ml beer ¼ 40 ml spirits ¼ 15 g pure alcohol). Wine accounted for more than 80% of the alcohol consumed by women in this population. To account simultaneously for the effects of several potential confounding factors, we performed unconditional multiple logistic regression, with maximum likelihood fitting, to obtain the odds ratios (ORs) of seromucinous cysts, their corresponding 95% confidence intervals (CI), and the test for trend when appropriate [9].
3. Results The distribution of cases and controls according to age and selected characteristics are presented in Table 1. Women with seromucinous cysts tended to be more educated, whereas no differences emerged between cases and control in regard to marital status, parity, body mass index and oral contraceptive use. The frequency of consumption of selected foods based on the best possible approximation of tertiles is shown in Table 2 and the corresponding odds ratios of seromucinous ovarian cysts are reported in Table 3. Consumption of milk, liver, carrots, eggs, ham and fish as well as coffee, tea and alcohol consumption were not
197
Table 1 Distribution of 225 casesa of seromucinous benign ovarian cysts and 450 controlsa according to selected factors (Italy 1984–1994) Seromucinous cysts
Control
No.
%
No.
%
100 48 77
44.5 21.3 34.2
206 93 151
45.8 20.7 33.5
Education (years) <7 7–11 12
71 73 81
31.6 32.4 36.0
171 149 130
38.0 33.1 28.9
Marital status Ever married Never married
156 69
69.3 30.7
291 159
64.7 35.3
Parity 0 1 2
103 44 77
46.0 19.6 34.4
195 89 166
43.3 19.8 36.9
Body mass index (kg/m2) <20 62 20–24 104 25 58
27.7 46.4 25.9
112 219 117
25.0 48.9 26.1
Oral contraceptives Ever users Never users
24.0 76.0
92 358
20.4 79.6
Age (years) 35 36–45 46
54 171
a
In some cases the sum does not add up to the total because of missing values.
Table 2 Distribution of 225 casesa of seromucinous cysts and 450 controlsa according to selected foods Food item
Milk Beef and other red meat Liver Carrots Green vegetables Fresh fruit Eggs Ham Fish Cheese Whole-grain foods Butter Margarine Oil Coffee Tea Total alcohol intake a
Frequency of consumption (no. of cases/no. of controls) 1 (low)
2 (intermediate)
3 (high)
62/145 62/165 119/209 86/178 79/124 40/68 41/115 63/157 84/172 85/186 178/308 125/283 204/384 44/70 45/93 181/344 114/200
122/224 58/145 106/240 49/111 94/174 76/120 54/104 71/128 105/186 42/116 26/77 86/147 21/66 147/337 95/209 44/104 48/126
41/81 105/140 90/161 52/152 109/262 130/231 91/165 36/92 98/148 21/65 14/20 34/43 84/147 63/124
For some items, the sum of strata does not add to the total because of missing values.
198
F. Chiaffarino et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
Table 3 Odds ratio estimates of seromucinous ovarian cysts according to frequency of consumption of selected foods Food item
Milk Beef and other red meat Liver Carrots Green vegetables Fresh fruit Eggs Ham Fish Cheese Whole-grain foods Butter Margarine Oil Coffee Tea Total alcohol intake
Table 4 Odds ratios and corresponding 95% confidence intervals for an intake increase of one serving of selected food groups per day
Odds ratio estimatesa (95% CI)
Odds ratiosa (95% CI)
2 (intermediate)
3 (high)
w2 (trend)
1.3 (0.9–1.9) 1.2 (0.8–1.9)
1.3 (0.8–2.2) 2.7 (1.7–4.1)
1.5 20.9, P ¼ 0.0001
0.7 0.9 0.9 1.0 1.5 1.6 1.1 0.8 0.6 1.4 0.6 0.6 1.0 0.7 0.6
(0.5–1.0) (0.6–1.4) (0.6–1.3) (0.6–1.7) (0.9–2.5) (1.0–2.4) (0.8–1.7) (0.5–1.2) (0.3–1.0) (1.0–2.0) (0.4–1.0) (0.4–1.0) (0.6–1.5) (0.5–1.1) (0.4–1.0)
1.1 0.5 0.7 1.6 1.4 0.8 1.5 0.5 1.4
(0.7–1.6) (0.3–0.8) (0.4–1.1) (1.0–2.4) (0.9–2.2) (0.5–1.3) (1.0–2.1) (0.3–0.9) (0.7–3.0)
1.2 (0.6–2.2) 1.2 (0.8–1.9) 0.9 (0.6–1.3)
3.4 0.2 7.1, P ¼ 0.008 3.8, P ¼ 0.05 3.5 2.8 0.4 3.9, P ¼ 0.05 7.7, P ¼ 0.006 3.1 3.3 0.03 0.8 2.1 1.1
Reference category: low frequency of consumption. CI: confidence interval. a Multiple logistic regression estimates including terms for age, education and calendar year at interview.
significantly related to ovarian cysts. No association was observed with fat (butter, margarine and oil) consumption. Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for green vegetables (OR ¼ 0:5 for the highest tertile of intake), fresh fruit (OR ¼ 0:7) and whole grain foods (OR ¼ 0:5), whereas increased risk was associated with beef and other red meat (OR ¼ 2:7) and cheese (OR ¼ 1:5). The tests for linear trend in risk were statistically significant. All food groups significantly associated to ovarian cysts risk were then simultaneously included in the same multiple logistic model, to allow for mutual confounding. The estimates for highest versus less frequent consumption levels were 2.7 (95% CI 1.8–4.3) for beef and other red meat, 0.6 (95% CI 0.3–0.9) for green vegetables and 1.4 (95% CI 1.0– 2.2) for cheese. The relation with fruit and with whole grain foods were limited and no more significant: 0.9 (95% CI 0.5–1.4) for fruit and 0.7 (95% CI 0.4–1.2) for whole grain foods (data not shown in table). It is however not simple to interpret this model because of the collinearity between various foods. In Table 4 the ORs for an intake increase of one serving per day of each food group significantly related to ovarian cancer risk are presented in strata of age and education. The associations were generally consistent in strata of age and education; the direct relation of meat and cheese were apparently stronger in older women, but no significant heterogeneity was observed.
Beef and other red meat
Green vegetables
Cheese
Total series
3.6 (2.1–6.3)
0.7 (0.5–0.9)
1.6 (1.0–2.6)
Age (years) <38 38
2.6 (1.2–5.5) 5.8 (2.5–13.5)
0.6 (0.4–0.9) 0.8 (0.5–1.2)
1.2 (0.7–2.3) 2.2 (1.1–4.5)
Education (years) <7 4.6 (1.7–12.1) 7–11 3.5 (1.2–10.0) 12 3.2 (1.3–8.2)
0.7 (0.4–1.2) 0.5 (0.3–0.9) 0.7 (0.4–1.2)
0.8 (0.3–2.1) 2.8 (1.3–6.2) 1.3 (0.6–3.1)
CI: confidence interval. a Derived from multiple logistic regression equation including terms for age, education and calendar year at interview, plus the above listed variables.
4. Discussion The dietary section in this study was restricted to a few selected indicator foods. Available information, in fact, was limited to the number of portions per week of a restricted list of dietary items, with no quantitative estimate of portion size. However, a major role of information bias is unlikely, since the possible relation between diet and seromucinous cysts was probably unknown to interviewers and the majority of the subjects interviewed. The diet questionnaire, moreover, was satisfactorily reproducible [7,8]. Likewise, a major effect of selection bias is unlikely because we included in the control group only women with acute conditions and excluded women with digestive-tract diseases or any condition that could be related to long term dietary changes. Further, a specific attempt was made to collect dietary information before the first diagnosis of seromucinous cysts. Very little is known on the nutritional epidemiology of benign ovarian cysts, and the main published study is essentially negative [3,4], with the only possible exception of an association with polynsaturated fats. In the same study, moreover, there was an inverse relation (but not statistically significant) between carotenoids and serous benign ovarian tumors, which is consistent with the result of the present study for vegetable and fruit. Like seromucinous carcinomas, benign seromucinous cysts originate from ovarian epithelium. Their common origin suggests that benign and malignant lesions may share similar etiological profiles. Our findings on dietary factors should, therefore, be considered in comparison with the epidemiological data of ovarian cancer [10]. In our study a frequent consumption of meat and cheese increased the risk of seromucinous ovarian cysts. Several studies showed a positive association between various types of meat and ovarian cancer risk [11–14]. In a multicentric
F. Chiaffarino et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
Italian case–control study on ovarian cancer (1031 cases) the OR for the highest quintile of red meat intake compared to the lowest one was 1.53 [11] and in a case–control study from Japan women reporting daily meat intake had an OR for ovarian cancer of 3.1 [12]. A direct association between fat intake and risk of ovarian cancer has been reported from a few case–control studies [15,16], although the relation was not homogenous for various types of fat. Olive oil in particular, showed a modest protective effect [17]. In our study, measures of fats intake were not associated with seromucinous ovarian cysts risk but cheese, an important source of saturated fat in our population, was directly associated with risk. A case–control study on ovarian cancer related to Italian population reported a protective effect of vegetables and whole grain [16], reflecting the results of seromucinous cysts in the present study: the reduction of risk of seromucinous cysts from green vegetables was more consistent than that of fresh fruit, and the association with fruit was no longer significant after the inclusion in multivariate analysis of all food groups significantly associated to ovarian cysts. The protective effect of vegetables on seromucinous ovarian cysts is in agreement with the well-established evidence of a beneficial effect of green vegetables on several epithelial cancers [18–20] and could be attributed to several constituent substances of vegetables, including anti-oxidants, vitamins, flavonoids and other micronutrients [21,22]. Our results show a inverse relation between whole grain food intake and seromucinous ovarian cysts risk. Whole grain foods share with vegetables a number of constituents, including fibers, anti-oxidants and phytoestrogens. The phytoestrogens have a diphenolic structure similar to estrogenic compounds and are related to sex hormone metabolism, behaving both as estrogenic or antiestrogenic compounds [22,23]. This may explain, at least in part, the protective effect suggested for whole grain foods on hormone-related neoplasms [24]. Women with ovarian malignant neoplasia could modify their dietary habits following a general gastrointestinal malaise, but this potential source of bias is less likely for women with benign conditions. In fact, women with ovarian cysts, a generally asymptomatic disease, are less likely to change the dietary habits; it is likely that in case–control study on benign neoplasia reported intakes reflect the actual consumption. The intake of vegetables and whole grain foods may be a general indicator of more health-oriented attitudes towards diet and other lifestyle habits. However, a greater attention to health may also favor the diagnosis the cysts, producing a underestimate of the real association. Social determinants of gynecologic surgery also are well recognized. Surgery for cysts or other benign neoplastic conditions, such as breast disease and uterine fibroids, is more frequent in more educated women of higher social classes [25] and may reflect the greater attention that better-educated women pay to relatively minor health problems.
199
In conclusion, the inverse relation with vegetables, fruit and whole-grain is of potential interest in defining a low risk diet for seromucinous ovarian cysts, whereas with a high risk one is characterized by elevated consumption of meat and cheese.
Acknowledgements This study was partially supported by a grant of Associazione Italiana per la Ricerca sul Cancro, Milano.
References [1] Ingram DM, Bennett FC, Willcox D, de Klerk N. Effect of low-fat diet on female sex hormone levels. JNCI 1987;79:1225–9. [2] Fentiman IS, Caleffi M, Wang DY, et al. The binding of blood-borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer. Nutr Cancer 1988;11:101–6. [3] Britton JA, Westhoff C, Howe G, Gammon MD. Diet and benign ovarian tumors (United States). Cancer Causes Control 2000;11:389– 401. [4] Britton JA, Westhoff C, Howe GR, Gammon MD. Lactose and benign ovarian tumours in a case–control study. Br J Cancer 2000; 83:1552–5. [5] Parazzini F, Moroni S, Negri E, La Vecchia C, Mezzopane R, Crosignani PG. Risk factors for seromucinous benign ovarian cysts in northern Italy. J Epidemiol Comm Health 1996;51:449–52. [6] Parazzini F, La Vecchia C, Franceschi S, Negri E, Cecchetti G. Risk factors for endometrioid, mucinous and serous benign ovarian cysts. Int J Epidemiol 1989;18:108–12. [7] La Vecchia C, Decarli A, Franceschi S, Gentile A, Negri E, Parazzini F. Dietary factors and the risk of breast cancer. Nutr Cancer 1987;10: 205–14. [8] D’Avanzo B, La Vecchia C, Katsouyanni K, Negri E, Trichopoulos D. An assessment, and reproducibility of food frequency data provided by hospital controls. Eur J Cancer Prev 1997;6:288–93. [9] Baker RJ, Nelder JA. The GLIM System release. Oxford: Numerical Algorithms Group; 1978. [10] Parazzini F, Franceschi S, La Vecchia C, Fasoli M. The epidemiology of ovarian cancer. Gynecol Oncol 1991;43:9–23. [11] Bosetti C, Negri E, Franceschi S, et al. Diet and ovarian cancer risk: a case–control study in Italy. Int J Cancer 2001;93:911–5. [12] Mori M, Harabuchi I, Miyake H, Casagrande JT, Henderson BE, Ross RK. Reproductive, genetic, and dietary risk factors for ovarian cancer. Am J Epidemiol 1988;128:771–7. [13] Tavani A, La Vecchia C, Gallus S, et al. Red meat intake and cancer risk: a study in Italy. Int J Cancer 2000;86:425–8. [14] Kushi LH, Mink PJ, Folsom AR, et al. Prospective study of diet and ovarian cancer. Am J Epidemiol 1999;149:21–31. [15] Shu XO, Gao YT, Yuan JM, Ziegler RG, Brinton LA. Dietary factors and epithelial ovarian cancer. Br J Cancer 1989;59:92–6. [16] La Vecchia C, Decarli A, Negri E, et al. Dietary factors and the risk of epithelial ovarian cancer. J Natl Cancer Inst 1987;79:663–9. [17] Tzonou A, Hsieh C, Polychronopoulou A, et al. Diet and ovarian cancer: a case–control study in Greece. Int J Cancer 1993;55:411–4. [18] Soler M, Bosetti C, Franceschi S, et al. Fiber intake and the risk of oral, pharyngeal and esophageal cancer. Int J Cancer 2001;91:283–7. [19] Negri E, Franceschi S, Parpinel M, La Vecchia C. Fiber intake in risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 1998;7:667– 71. [20] La Vecchia C, Ferraroni M, Franceschi S, Mezzetti M, Decarli A, Negri E. Fibers and breast cancer risk. Nutr Cancer 1997;28:264–9.
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[21] La Vecchia C, Chatenoud L, Franceschi S, Soler M, Parazzini F, Negri E. Vegetables and fruit and human cancer: update of an Italian study. Int J Cancer 1999;82:151–2. [22] Potter JD, Steinmetz K. Vegetables, fruit and phytoestrogens as preventive agents. In: Stewart BW, McGregor D, Kleihues P, editors. Principles and chemoprevention. Lyon: IARC Scientific Publ. Int. Agency Res Cancer; 1996. p. 139.
[23] Slavin J, Jacobs D, Marquart L. Whole-grain consumption and chronic disease: protective mechanisms. Nutr Cancer 1997;27:14–21. [24] Chatenoud L, Tavani A, La Vecchia C, et al. Whole grain food intake and cancer risk. Int J Cancer 1998;77:24–8. [25] Parazzini F, La Vecchia C, Negri E, Tozzi L. Determinants of hysterectomy and oophorectomy in Northern Italy. Rev Epidemiol Sante Publique 1993;41:480–6.
Diet and risk of seromucinous benign ovarian cysts Francesca Chiaffarinoa, Fabio Parazzinia,b,*, Matteo Suracea, Guido Benzib, Vito Chianteraa, Carlo La Vecchiaa,c a
Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, via Eritrea, Milano 62-20157, Italy Clinica Ostetrico Ginecologica, Istituto Clinico di Perfezionamento, Universita` di Milano, Milano, Italy c Istituto di Statistica Medica e Biometria, Universita` degli Studi di Milano, Milano, Italy
b
Received 20 June 2002; received in revised form 20 January 2003; accepted 3 February 2003
Abstract Objective: To analyze the relation between selected dietary indicators and the risk of seromucinous benign ovarian cysts. Study design: We used data from a case–control study on risk factors for benign ovarian cysts conducted in Italy between 1984 and 1994. Cases included 225 women with a histologically confirmed diagnosis of benign seromucinous ovarian neoplasm dating back no more than 2 years. Controls were 450 women below the age of 65 years admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions. Results: Women with seromucinous cysts reported more frequent consumption of beef and other red meat and cheese and less frequent consumption of green vegetables. The multivariate odds ratios (ORs) in highest versus less frequent consumption levels were 2.7 (95% confidence interval (CI) 1.8–4.3) for beef and other red meat, 0.6 (95% CI 0.3–0.9) for green vegetables and 1.4 (95% CI 1.0–2.2) for cheese. Conclusion: Seromucinous benign ovarian cysts are associated with beef and cheese consumption, whereas high intake of green vegetables seems to have a protective effect. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Diet; Risk factors; Ovarian cysts
1. Introduction
2. Methods
Relatively little is known concerning the etiology of seromucinous ovarian cysts, although hormonal factors appear to be important. It is known that nutrition and diet are related to sex hormones and their binding proteins, and this provides a plausible biological explanation for a potential association between diet and seromucinous ovarian cysts [1,2]. A population-based study, of 668 cases and 347 controls analyzed, conducted in metropolitan area of New York, USA, has recently suggested that polyunsaturated and hence vegetable fat may increase the risk of benign ovarian tumors [3]. None of the others nutrients considered, included lactose intake [4] were related to benign ovarian tumors. Using data from a case–control study, conducted in northern Italy, we have considered the potential role of selected foods in the etiology of seromucinous ovarian cancer.
Between 1984 and 1994 we conducted a case–control study of benign ovarian cysts, whose design and methods has been previously described [5,6]. Briefly, cases included 225 women aged less than 65 years (median age 38 years; age range 15–64 years) with a histologically confirmed diagnosis of benign seromucinous ovarian neoplasm, admitted to a network of obstetrics and gynecology departments in Milan. The clinical diagnoses of cases dated back no more than 2 years. Controls were women below the age of 65 years admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions to the Ospedale Maggiore (including the four major teaching and general hospitals in Milan) and several university clinics, serving a catchment area comparable to that of the hospitals where cases had been identified. They were recruited within the framework of a case–control study of female genital neoplasm. Out of a total of 2654 subjects interviewed, 450 controls were identified (age range 16–64 years; median age 38 years), matched with cases in a 1:2 ratio, and randomly selected within strata of 5 years age groups and calendar years of interview. Of these, 34% were
* Corresponding author. Tel.: þ39-02-390141; fax: þ39-02-33200231. E-mail address: [email protected] (F. Parazzini).
0301-2115/$ – see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00115-5
F. Chiaffarino et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
admitted for traumatic conditions (mostly fractures and sprains), 26% had non-traumatic orthopedic disorders (mostly low back pain and disc disorders), 17% acute abdominal diseases requiring surgery, and 23% other miscellaneous illnesses, such as disorders of the ear, nose, throat, or teeth. Trained interviewers identified and questioned cases and controls. All interviews were conducted in hospital. Less than 3% of cases and controls refused to be interviewed. Information was obtained, using a structured questionnaire, on general sociodemographic factors, personal characteristics and habits, gynecological and obstetric history, and lifetime oral contraceptive use. Subjects were also asked about frequency of consumption per week of selected dietary items (including the major sources of retinoids and carotenoids in the Italian diet), such as milk, beef and other red meat, liver, carrots, green vegetables, fresh fruit, eggs, ham, fish, cheese, whole grain in the year before interview. Moreover, the intake of metilxantine (coffee, tea, cola) and of alcoholic beverage (wine, beer, spirits) were collect as number of cup or glasses/day, number of days/week and duration (years) of consumption. Subjective scores (low, intermediate and high) were used to collect information on fat intake (butter, margarine and oil) and consumption of whole grain foods. Reproducibility of the questionnaire was satisfactory [7,8]. The cut-off for the analysis of dietary factors were based on the best possible approximation of tertiles. An estimate of the total daily average alcohol intake was derived assuming a comparable ethanol content in each type of beverage (125 ml wine ¼ 333 ml beer ¼ 40 ml spirits ¼ 15 g pure alcohol). Wine accounted for more than 80% of the alcohol consumed by women in this population. To account simultaneously for the effects of several potential confounding factors, we performed unconditional multiple logistic regression, with maximum likelihood fitting, to obtain the odds ratios (ORs) of seromucinous cysts, their corresponding 95% confidence intervals (CI), and the test for trend when appropriate [9].
3. Results The distribution of cases and controls according to age and selected characteristics are presented in Table 1. Women with seromucinous cysts tended to be more educated, whereas no differences emerged between cases and control in regard to marital status, parity, body mass index and oral contraceptive use. The frequency of consumption of selected foods based on the best possible approximation of tertiles is shown in Table 2 and the corresponding odds ratios of seromucinous ovarian cysts are reported in Table 3. Consumption of milk, liver, carrots, eggs, ham and fish as well as coffee, tea and alcohol consumption were not
197
Table 1 Distribution of 225 casesa of seromucinous benign ovarian cysts and 450 controlsa according to selected factors (Italy 1984–1994) Seromucinous cysts
Control
No.
%
No.
%
100 48 77
44.5 21.3 34.2
206 93 151
45.8 20.7 33.5
Education (years) <7 7–11 12
71 73 81
31.6 32.4 36.0
171 149 130
38.0 33.1 28.9
Marital status Ever married Never married
156 69
69.3 30.7
291 159
64.7 35.3
Parity 0 1 2
103 44 77
46.0 19.6 34.4
195 89 166
43.3 19.8 36.9
Body mass index (kg/m2) <20 62 20–24 104 25 58
27.7 46.4 25.9
112 219 117
25.0 48.9 26.1
Oral contraceptives Ever users Never users
24.0 76.0
92 358
20.4 79.6
Age (years) 35 36–45 46
54 171
a
In some cases the sum does not add up to the total because of missing values.
Table 2 Distribution of 225 casesa of seromucinous cysts and 450 controlsa according to selected foods Food item
Milk Beef and other red meat Liver Carrots Green vegetables Fresh fruit Eggs Ham Fish Cheese Whole-grain foods Butter Margarine Oil Coffee Tea Total alcohol intake a
Frequency of consumption (no. of cases/no. of controls) 1 (low)
2 (intermediate)
3 (high)
62/145 62/165 119/209 86/178 79/124 40/68 41/115 63/157 84/172 85/186 178/308 125/283 204/384 44/70 45/93 181/344 114/200
122/224 58/145 106/240 49/111 94/174 76/120 54/104 71/128 105/186 42/116 26/77 86/147 21/66 147/337 95/209 44/104 48/126
41/81 105/140 90/161 52/152 109/262 130/231 91/165 36/92 98/148 21/65 14/20 34/43 84/147 63/124
For some items, the sum of strata does not add to the total because of missing values.
198
F. Chiaffarino et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 196–200
Table 3 Odds ratio estimates of seromucinous ovarian cysts according to frequency of consumption of selected foods Food item
Milk Beef and other red meat Liver Carrots Green vegetables Fresh fruit Eggs Ham Fish Cheese Whole-grain foods Butter Margarine Oil Coffee Tea Total alcohol intake
Table 4 Odds ratios and corresponding 95% confidence intervals for an intake increase of one serving of selected food groups per day
Odds ratio estimatesa (95% CI)
Odds ratiosa (95% CI)
2 (intermediate)
3 (high)
w2 (trend)
1.3 (0.9–1.9) 1.2 (0.8–1.9)
1.3 (0.8–2.2) 2.7 (1.7–4.1)
1.5 20.9, P ¼ 0.0001
0.7 0.9 0.9 1.0 1.5 1.6 1.1 0.8 0.6 1.4 0.6 0.6 1.0 0.7 0.6
(0.5–1.0) (0.6–1.4) (0.6–1.3) (0.6–1.7) (0.9–2.5) (1.0–2.4) (0.8–1.7) (0.5–1.2) (0.3–1.0) (1.0–2.0) (0.4–1.0) (0.4–1.0) (0.6–1.5) (0.5–1.1) (0.4–1.0)
1.1 0.5 0.7 1.6 1.4 0.8 1.5 0.5 1.4
(0.7–1.6) (0.3–0.8) (0.4–1.1) (1.0–2.4) (0.9–2.2) (0.5–1.3) (1.0–2.1) (0.3–0.9) (0.7–3.0)
1.2 (0.6–2.2) 1.2 (0.8–1.9) 0.9 (0.6–1.3)
3.4 0.2 7.1, P ¼ 0.008 3.8, P ¼ 0.05 3.5 2.8 0.4 3.9, P ¼ 0.05 7.7, P ¼ 0.006 3.1 3.3 0.03 0.8 2.1 1.1
Reference category: low frequency of consumption. CI: confidence interval. a Multiple logistic regression estimates including terms for age, education and calendar year at interview.
significantly related to ovarian cysts. No association was observed with fat (butter, margarine and oil) consumption. Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for green vegetables (OR ¼ 0:5 for the highest tertile of intake), fresh fruit (OR ¼ 0:7) and whole grain foods (OR ¼ 0:5), whereas increased risk was associated with beef and other red meat (OR ¼ 2:7) and cheese (OR ¼ 1:5). The tests for linear trend in risk were statistically significant. All food groups significantly associated to ovarian cysts risk were then simultaneously included in the same multiple logistic model, to allow for mutual confounding. The estimates for highest versus less frequent consumption levels were 2.7 (95% CI 1.8–4.3) for beef and other red meat, 0.6 (95% CI 0.3–0.9) for green vegetables and 1.4 (95% CI 1.0– 2.2) for cheese. The relation with fruit and with whole grain foods were limited and no more significant: 0.9 (95% CI 0.5–1.4) for fruit and 0.7 (95% CI 0.4–1.2) for whole grain foods (data not shown in table). It is however not simple to interpret this model because of the collinearity between various foods. In Table 4 the ORs for an intake increase of one serving per day of each food group significantly related to ovarian cancer risk are presented in strata of age and education. The associations were generally consistent in strata of age and education; the direct relation of meat and cheese were apparently stronger in older women, but no significant heterogeneity was observed.
Beef and other red meat
Green vegetables
Cheese
Total series
3.6 (2.1–6.3)
0.7 (0.5–0.9)
1.6 (1.0–2.6)
Age (years) <38 38
2.6 (1.2–5.5) 5.8 (2.5–13.5)
0.6 (0.4–0.9) 0.8 (0.5–1.2)
1.2 (0.7–2.3) 2.2 (1.1–4.5)
Education (years) <7 4.6 (1.7–12.1) 7–11 3.5 (1.2–10.0) 12 3.2 (1.3–8.2)
0.7 (0.4–1.2) 0.5 (0.3–0.9) 0.7 (0.4–1.2)
0.8 (0.3–2.1) 2.8 (1.3–6.2) 1.3 (0.6–3.1)
CI: confidence interval. a Derived from multiple logistic regression equation including terms for age, education and calendar year at interview, plus the above listed variables.
4. Discussion The dietary section in this study was restricted to a few selected indicator foods. Available information, in fact, was limited to the number of portions per week of a restricted list of dietary items, with no quantitative estimate of portion size. However, a major role of information bias is unlikely, since the possible relation between diet and seromucinous cysts was probably unknown to interviewers and the majority of the subjects interviewed. The diet questionnaire, moreover, was satisfactorily reproducible [7,8]. Likewise, a major effect of selection bias is unlikely because we included in the control group only women with acute conditions and excluded women with digestive-tract diseases or any condition that could be related to long term dietary changes. Further, a specific attempt was made to collect dietary information before the first diagnosis of seromucinous cysts. Very little is known on the nutritional epidemiology of benign ovarian cysts, and the main published study is essentially negative [3,4], with the only possible exception of an association with polynsaturated fats. In the same study, moreover, there was an inverse relation (but not statistically significant) between carotenoids and serous benign ovarian tumors, which is consistent with the result of the present study for vegetable and fruit. Like seromucinous carcinomas, benign seromucinous cysts originate from ovarian epithelium. Their common origin suggests that benign and malignant lesions may share similar etiological profiles. Our findings on dietary factors should, therefore, be considered in comparison with the epidemiological data of ovarian cancer [10]. In our study a frequent consumption of meat and cheese increased the risk of seromucinous ovarian cysts. Several studies showed a positive association between various types of meat and ovarian cancer risk [11–14]. In a multicentric
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Italian case–control study on ovarian cancer (1031 cases) the OR for the highest quintile of red meat intake compared to the lowest one was 1.53 [11] and in a case–control study from Japan women reporting daily meat intake had an OR for ovarian cancer of 3.1 [12]. A direct association between fat intake and risk of ovarian cancer has been reported from a few case–control studies [15,16], although the relation was not homogenous for various types of fat. Olive oil in particular, showed a modest protective effect [17]. In our study, measures of fats intake were not associated with seromucinous ovarian cysts risk but cheese, an important source of saturated fat in our population, was directly associated with risk. A case–control study on ovarian cancer related to Italian population reported a protective effect of vegetables and whole grain [16], reflecting the results of seromucinous cysts in the present study: the reduction of risk of seromucinous cysts from green vegetables was more consistent than that of fresh fruit, and the association with fruit was no longer significant after the inclusion in multivariate analysis of all food groups significantly associated to ovarian cysts. The protective effect of vegetables on seromucinous ovarian cysts is in agreement with the well-established evidence of a beneficial effect of green vegetables on several epithelial cancers [18–20] and could be attributed to several constituent substances of vegetables, including anti-oxidants, vitamins, flavonoids and other micronutrients [21,22]. Our results show a inverse relation between whole grain food intake and seromucinous ovarian cysts risk. Whole grain foods share with vegetables a number of constituents, including fibers, anti-oxidants and phytoestrogens. The phytoestrogens have a diphenolic structure similar to estrogenic compounds and are related to sex hormone metabolism, behaving both as estrogenic or antiestrogenic compounds [22,23]. This may explain, at least in part, the protective effect suggested for whole grain foods on hormone-related neoplasms [24]. Women with ovarian malignant neoplasia could modify their dietary habits following a general gastrointestinal malaise, but this potential source of bias is less likely for women with benign conditions. In fact, women with ovarian cysts, a generally asymptomatic disease, are less likely to change the dietary habits; it is likely that in case–control study on benign neoplasia reported intakes reflect the actual consumption. The intake of vegetables and whole grain foods may be a general indicator of more health-oriented attitudes towards diet and other lifestyle habits. However, a greater attention to health may also favor the diagnosis the cysts, producing a underestimate of the real association. Social determinants of gynecologic surgery also are well recognized. Surgery for cysts or other benign neoplastic conditions, such as breast disease and uterine fibroids, is more frequent in more educated women of higher social classes [25] and may reflect the greater attention that better-educated women pay to relatively minor health problems.
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In conclusion, the inverse relation with vegetables, fruit and whole-grain is of potential interest in defining a low risk diet for seromucinous ovarian cysts, whereas with a high risk one is characterized by elevated consumption of meat and cheese.
Acknowledgements This study was partially supported by a grant of Associazione Italiana per la Ricerca sul Cancro, Milano.
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