Ovarian cancer risk factors

Prevention

Preventable cases of ovarian cancer, UK

Lack of breastfeeding

Ovarian cancer cases linked to breastfeeding for less than 6 months or not at all, UK

Smoking

Ovarian cancer cases linked to exposure to tobacco smoke, UK

Hormone replacement

Ovarian cancer cases linked to the use of hormone replacement therapy (HRT), UK

21% of ovarian cancer cases each year in the UK are linked to major lifestyle and other risk factors.[1]

Ovarian cancer risk is associated with a number of risk factors.[2-4]

Ovarian Cancer Risk Factors

Increases risk ('sufficient' or 'convincing' evidence) May increase risk ('limited' or 'probable' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)
  • Asbestos
  • Hormone replacement therapy (oestrogen-only)
  • Tobacco smoking
  • Talc-based body powder (perineal use)
  • X-radiation, gamma radiation
  • Adult-attained height
  • Oral contraceptives
  • Breastfeeding
  • Non-starchy vegetables (not salted or pickled)

International Agency for Research on Cancer (IARC) and The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifications.

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Ovarian cancer risk is associated with factors affecting lifetime number of (and breaks between) ovulations, and/or sex hormone levels (oestrogen, progesterone and androgens). Ovulation causes structural changes to the ovary which may stimulate cancer development, and hormonal factors may compound this or have their own independent effects.[1-3] Having more children, breastfeeding, or using oral contraceptives (OCs) decreases the number of ovulations.

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Current use of postmenopausal oestrogen hormone replacement therapy (HRT) is classified by the International Agency for Research on Cancer (IARC) as a cause of ovarian cancer.[1] An estimated 1% of ovarian cancer cases in the UK are linked to HRT use.[2]

Ovarian cancer risk is 53% higher in long-term (5+ years) current oestrogen-only HRT users, compared with never users, a cohort study showed.[3]

Ovarian cancer risk is 17% higher in long-term (5+ years) oestrogen-progesterone HRT users, compared with never users, a cohort study showed.[3]

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Ovarian cancer risk varies with circulating androstenedione levels, a nested case-control study showed; this association varies with ovarian cancer type and menopausal status.[1] Ovarian cancer risk is not associated with circulating testosterone levels.[1]

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Tobacco smoking is classified by the International Agency for Research on Cancer (IARC) as a cause of ovarian cancer.[1] An estimated 3% of ovarian cancer cases in the UK are linked to smoking tobacco.[2]

Ovarian mucinous cancer risk is 31-49% higher in current smokers compared with never-smokers, meta- and pooled analyses have shown.[3,4] Risk increases with smoking duration.[3,4] Ovarian mucinous borderline malignant tumour risk is 83-125% higher in current versus never-smokers.[3,4]

Ovarian clear cell and ovarian endometrioid cancer risk may be lower in current versus never-smokers, but evidence is mixed.[3,4] Other ovarian cancer types are not associated smoking.[3,4]

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Asbestos is classified by the International Agency for Research on Cancer (IARC) as a cause of ovarian cancer.[1]

Ovarian cancer mortality risk is higher in women occupationally exposed to asbestos, meta-analyses have shown; however the evidence is limited by erroneous inclusion of peritoneal mesothelioma with ovarian cancer cases, potential confounding by other risk factors, and lack of evidence for an association with ovarian cancer incidence.[2,3]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Accessed December 2014.
  2. Reid A, de Klerk N, Musk AW. Does exposure to asbestos cause ovarian cancer? A systematic literature review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2011;20(7):1287-95.
  3. Camargo MC, Stayner LT, Straif K, et al. Occupational exposure to asbestos and ovarian cancer: a meta-analysis. Environ Health Perspect 2011;119(9):1211-7.
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Talc-based body powder used perineally Open a glossary item is classified by the International Agency for Research on Cancer (IARC) as a probable cause of ovarian cancer.[1]

Ovarian cancer risk is 24-35% higher in women who have ever used body powder perineally/genitally versus those who have not, meta- and pooled analyses of case-controls studies have shown.[2,3] However, recall bias (cases more likely than controls to recall exposure to possible risk factors) may have influenced this, as ovarian cancer risk is not associated with perineal powder use in cohort studies.[3,4] Ovarian cancer risk is not associated with non-genital talc-based body powder use.[5]

This association with ovarian cancer risk may be due to the mineral talc in body powders, though not all body powders today contain talc; it may also be due to asbestos traces in some body powders made before the 1970s.[3]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Accessed December 2014.
  2. Terry KL, Karageorgi S, Shvetsov YB, et al. Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls. Cancer Rev Pres (Phila) 2013;6(8):811-21.
  3. Langseth H, Hankinson SE, Siemiatycki J, et al. Perineal use of talc and risk of ovarian cancer. J Epidemiol Community Health 2008;62(4):358-60.
  4. Houghton SC, Reeves KW, Hankinson SE, et al. Perineal powder use and risk of ovarian cancer. J Natl Cancer Inst 2014;106(9). pii: dju208.
  5. Terry KL, Karageorgi S, Shvetsov YB, et al. Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls. Cancer Rev Pres (Phila) 2013;6(8):811-21.
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X radiation and gamma radiation is classified by the International Agency for Research on Cancer (IARC) as a probable cause of ovarian cancer.[1]

A very small number of ovarian cancer cases may be associated with radiotherapy for previous cancer, specifically breast cancer.[2] However associations between breast and ovarian cancers are probably due more to shared genetic or hormonal risk factors; indeed radiotherapy has been associated with decreased ovarian cancer risk in breast cancer survivors.[3]

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Around 3% of ovarian cancer cases occur in women with a family history of ovarian cancer, a cohort study showed.[1] Ovarian cancer risk is 2.7-3.5 times higher in women whose mother or sister has/had ovarian cancer, compared with women with no such family history, cohort studies have shown; risk may be higher if the affected relative was diagnosed at a younger age.[2,3]

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Ovarian cancer risk is higher in women whose sibling has/had stomach, liver, breast, prostate, or connective tissue cancer, or melanoma; or whose parent has/had breast or liver cancer, a cohort study showed.[1] Ovarian cancer risk is higher in families with a history of breast cancer compared with the general population, even when when BRCA1 Open a glossary item or BRCA2 Open a glossary item mutations are not present, a cohort study showed.[2]

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Inherited conditions account for 5-15% of ovarian cancer cases; the majority of these hereditary cases are linked with BRCA1/2 mutations.[1]

Ovarian cancer risk is up to 65% higher in women with BRCA1 mutation, and up to 35% higher in women with BRCA2 mutation, versus women without these genes.[2,3] Ovarian cancer risk among BRCA1 mutation carriers is lower in those who have given birth to 4+ children versus none, those who have used oral contraceptives for a year or more, and those who have had tubal ligation; but is not associated with other reproductive factors, or hormone replacement therapy (HRT) use, a meta-analysis showed.[4] Ovarian cancer risk among BRCA2 mutation carriers is lower in oral contraceptives users but is not associated with reproductive factors or HRT use.[4]

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Around 7% of women with Lynch syndrome  develop ovarian cancer by age 70, a pooled analysis showed.[1] Around 21% of women with Peutz-Jeghers syndrome develop ovarian cancer aged 15-64, a meta-analysis showed.[2]

References

  1. Watson P, Vasen HF, Mecklin JP, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 2008;123(2):444-9.
  2. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119(6):1447-53.
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Ovarian cancer risk among hormone replacement therapy (HRT) never-users, and premenopausal women, is 10-13% higher per 5-unit body mass index (BMI) increment, meta-analyses have shown.[1,2] Ovarian cancer risk among HRT ever-users (presumably postmenopausal) is 5% lower per 5-unit BMI increment.[1] Ovarian cancer risk may only be increased in women with BMI above 28, a meta-analysis showed.[2]

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Greater adult attained height (as a marker of factors that promote linear growth in childhood) is classified by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) a probable cause of ovarian cancer.[1]

Ovarian cancer risk is 7-10% higher per 5cm increment in height, meta-analyses and a pooled analysis of Nordic data showed.[2-4]

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Ovarian cancer risk is 27-80% higher in women with endometriosis Open a glossary item, versus women without the disease and the general population respectively, a meta-analysis showed.[1] The association may differ by tumour type.[1]

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Ovarian cancer risk is 20-55% higher in diabetics compared with non-diabetics, meta-analyses have shown.[1,2]

Ovarian cancer risk among diabetics may be slightly higher in insulin users versus non-users.[3] Ovarian cancer risk among diabetics is not associated with metformin or pioglitazone use versus non-use.[4,5]

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Ovarian cancer risk is 24% higher in breast cancer survivors compared with the general population, a cohort study showed.[1] Ovarian cancer risk among breast cancer survivors is higher in those diagnosed with breast cancer at a younger age versus those diagnosed older, and higher risk is limited to oestrogen-receptor Open a glossary item (ER)-negative or ER-unknown breast cancer.[1]

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Ovarian cancer risk is higher in bowel cancer survivors compared with the general population, a cohort study showed; this is limited to those diagnosed with bowel cancer at a younger age, and largely limited to the period very shortly after bowel cancer diagnosis.[1]

These associations between primary breast and bowel cancers and subsequent ovarian cancer probably reflects the impact of BRCA mutations and Lynch syndrome, or shared hormonal risk factors.[1,2]

References

  1. Ahmed F, Goodman MT, Kosary C, et al. Excess risk of subsequent primary cancers among colorectal carcinoma survivors, 1975-2001. Cancer 2006;107(5 Suppl):1162-71.
  2. Schonfeld SJ, Berrington de Gonzalez A, Visvanathan K, et al. Declining second primary ovarian cancer after first primary breast cancer. J Clin Oncol 2013;31(6):738-43.
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Oral contraceptives (OCs) are classified by the International Agency for Research on Cancer (IARC) as protective against ovarian cancer.[1] An estimated 9% more ovarian cancer cases would occur each year in the UK, but for current and past use of OCs.[2]

Ovarian cancer risk is 25-28% lower in women who have ever used OCs compared with never-users, a meta-analysis showed.[3] Risk reduces further with longer duration of OC use; it is more than halved with 10+ years' use, a meta-analysis showed.[3] Ovarian cancer risk in OC ever-users remains reduced for at least 30 years after last use of OCs, though the protection may diminish over time.[3,4]

Among BRCA1/2 mutation carriers, ovarian cancer risk is almost halved among OC ever-users compared with never-users, a meta-analysis showed.[3,5]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Accessed December 2014.
  2. Parkin DM. Cancers attributable to exposure to hormones in the UK in 2010. Br J Cancer Dec 2011; 105 (S2):S42-S48.
  3. Havrilesky LJ, Gierisch JM, Moorman PG, et al. Oral contraceptive use for the primary prevention of ovarian cancer. Evid Rep Technol Assess (Full Rep). 2013;(212):1-514.
  4. Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, Hermon C, et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008;371(9609):303-14.
  5. Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis [PDF]. J Clin Oncol. 2013;31(33):4188-98.Oct 21.
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Breastfeeding is classified by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) as possibly protective against ovarian cancer, based on limited evidence.[1] An estimated 18% of ovarian cancers in the UK are linked to women breastfeeding each of their children for fewer than 6 months.[2]

Ovarian cancer risk is 24% lower in women who have ever breastfed, versus those who have never done so, meta-analyses have shown; risk decreases further with longer breastfeeding duration.[3,4]

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Consumption of non-starchy vegetables is classified by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) as possibly protective against ovarian cancer, based on limited evidence.[1]

Consumption of cruciferous vegetables and vegetables overall is not associated with ovarian cancer risk, meta- and pooled analyses have shown.[2,3]

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Ovarian cancer risk is lower in women with the following reproductive or medical factors, meta-and pooled analyses or systematic reviews have shown:

  • Higher parity (number of children given birth to).[1-3] Nulliparity (bearing no children) plus not breastfeeding are probably the mechanisms underlying higher ovarian cancer risk in infertile women, including those treated with ovarian stimulating drugs.[4-6]
  • Hysterectomy Open a glossary item – 27-31% lower risk (though some evidence of higher risk in women undergoing hysterectomy in more recent years, perhaps due to changes in average age at hysterectomy, surgical technique, or use of hormone replacement therapy (HRT) following hysterectomy).[7,8]
  • Tubal ligation – 30% lower risk, with variation by ovarian cancer subtype.[7]
  • Statins – 21% lower risk in users versus non-users, even lower risk in long-term (5+ years) users.[9]
  • Systemic lupus erythematosus Open a glossary item – 34% lower risk versus general population[10] (though some evidence of no association[11]).

References

  1. Högnäs E, Kauppila A, Pukkala E, et al. Cancer risk in women with 10 or more deliveries. Obstet Gynecol 2014;123(4):811-6.
  2. Bodelon C, Wentzensen N, Schonfeld SJ, et al. Hormonal risk factors and invasive epithelial ovarian cancer risk by parity. Br J Cancer 2013;109(3):769-76.
  3. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 2013;31(20):2607-18.
  4. Li LL, Zhou J, Qian XJ, et al. Meta-analysis on the possible association between in vitro fertilization and cancer risk. Int J Gynecol Cancer 2013;23(1):16-24.
  5. Tworoger SS, Fairfield KM, Colditz GA, et al. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 2007;166(8):894-901.
  6. Jensen A, Sharif H, Olsen JH, et al. Risk of breast cancer and gynecologic cancers in a large population of nearly 50,000 infertile Danish women. Am J Epidemiol 2008; 168(1):49-57.
  7. Rice MS, Murphy MA, Tworoger SS. Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis. J Ovarian Res 2012;5(1):13.
  8. Jordan SJ, Nagle CM, Coory MD, et al. Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta-analysis. Eur J Cancer 2013;49(17):3638-47.
  9. Liu Y, Qin A, Li T, et al. Effect of statin on risk of gynecologic cancers: a meta-analysis of observational studies and randomized controlled trials. Gynecol Oncol 2014;133(3):647-55.
  10. Bernatsky S, Ramsey-Goldman R, Foulkes WD, et al. Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis. Br J Cancer 2011;104(9):1478-81.
  11. Bernatsky S, Ramsey-Goldman R, Labrecque J, et al. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun 2013;42:130-5.
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The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) make no judgment on the association between ovarian cancer risk and dietary fibre; fruits; pulses (legumes); meat; poultry; fish; eggs; milk and dairy products; total fat; cholesterol; coffee; tea; alcohol; carbohydrate; lactose; protein; vitamin A; folate; vitamin C; vitamin E; recreational activity; body fatness; abdominal fatness; weight change and energy intake, due to limited evidence.[1]

Ovarian cancer risk is not associated with the following factors, meta- and pooled analyses or systematic reviews have shown:

  • Older age at menarche (though some evidence of lower risk in case-control studies).[2]
  • Polycystic ovary syndrome (PCOS) and ovarian cysts (though limited evidence of higher risk in younger women with PCOS).[3-6]
  • Aspirin[7,8] (though some evidence of lower risk particularly with daily low-dose aspirin[9,10]).
  • Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs)[7,8,10] (though some evidence of lower risk of mucinous ovarian cancer[8]).
  • Paracetamol (acetaminophen).[9,11,12]
  • Physical activity (though some evidence of lower risk in case-control studies).[13]
  • Birth weight.[14]
  • Vitamin D levels.[15,16]
  • Alcohol.[17-19]
  • Coffee.[20]
  • Red and processed meat.[21]
  • Fish.[22]
  • Dietary lycopene (postmenopausal women).[23]
  • Dairy products.[24,25]
  • Total dietary fat (though some evidence of higher risk, particularly for animal fats[26,27]).[28]
  • Fruit.[29]
  • Eggs (though some evidence of higher risk in case-control studies).[30]

References

  1. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR; 2007.
  2. Gong TT, Wu QJ, Vogtmann E, et al. Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies. Int J Cancer 2013;132(12):2894-900.
  3. Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2014;20(5):748-58.
  4. Greenlee RT, Kessel B, Williams CR, et al. Prevalence, incidence, and natural history of simple ovarian cysts among women >55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010;202(4):373.e1-9.
  5. Rossing MA, Cushing-Haugen KL, Wicklund KG, et al. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control 2008;19(10):1357-64.
  6. Borgfeldt C, Andolf E. Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand 2004;83(4):395-400.
  7. Ni X, Ma J, Zhao Y, et al. Meta-analysis on the association between non-steroidal anti-inflammatory drug use and ovarian cancer. Br J Clin Pharmacol. 2013;75(1):26-35.
  8. Murphy MA, Trabert B, Yang HP, et al. Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control 2012;23(11):1839-52.
  9. Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst 2014;106(2):djt431.
  10. Baandrup L, Faber MT, Christensen J, et al. Nonsteroidal anti-inflammatory drugs and risk of ovarian cancer: systematic review and meta-analysis of observational studies. Acta Obstet Gynecol Scand 2013;92(3):245-55.
  11. Bonovas S, Filioussi K, Sitaras NM. Paracetamol use and risk of ovarian cancer: a meta-analysis. Br J Clin Pharmacol 2006;62(1):113-21.
  12. Pinheiro SP, Tworoger SS, Cramer DW, et al. Use of nonsteroidal antiinflammatory agents and incidence of ovarian cancer in 2 large prospective cohorts. Am J Epidemiol 2009;169(11):1378-87.
  13. Zhong S, Chen L, Lv M, et al. Nonoccupational physical activity and risk of ovarian cancer: a meta-analysis. Tumour Biol 2014;35(11):11065-73.
  14. Yang TO, Reeves GK, Green J, et al. Birth weight and adult cancer incidence: large prospective study and meta-analysis. Ann Oncol 2014;25(9):1836-43.
  15. Prescott J, Bertrand KA, Poole EM, et al. Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies. Cancers (Basel) 2013;5(4):1577-600.
  16. Yin L, Grandi N, Raum E, et al. Meta-analysis: Circulating vitamin D and ovarian cancer risk. Gynecol Oncol. 2011;121(2):369-75.
  17. Genkinger JM, Hunter DJ, Spiegelman D, et al. Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies. Br J Cancer 2006; 94(5):757-62.
  18. Kelemen LE, Bandera EV, Terry KL, et al. Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium. BMC Cancer 2013;13:28.
  19. Rota M, Pasquali E, Scotti L, et al. Alcohol drinking and epithelial ovarian cancer risk. a systematic review and meta-analysis. Gynecol Oncol 2012;125(3):758-63.
  20. Braem MG, Onland-Moret NC, Schouten LJ, et al. Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis. Am J Clin Nutr 2012;95(5):1172-81.
  21. Wallin A, Orsini N, Wolk A. Red and processed meat consumption and risk of ovarian cancer: a dose-response meta-analysis of prospective studies. Br J Cancer 2011;104(7):1196-201.
  22. Jiang PY, Jiang ZB, Shen KX, et al. Fish intake and ovarian cancer risk: a meta-analysis of 15 case-control and cohort studies. PLoS One 2014;9(4):e94601.
  23. Li X, Xu J. Meta-analysis of the association between dietary lycopene intake and ovarian cancer risk in postmenopausal women. Sci Rep 2014;4:4885.
  24. Genkinger JM, Hunter DJ, Spiegelman D, et al. Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev 2006;15(2):364-72.
  25. Liu J, Tang W, Sang L, et al. Milk, yogurt, and lactose intake and ovarian cancer risk: a meta-analysis. Nutr Cancer 2015;67(1):68-72.
  26. Huncharek M, Kupelnick B. Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies. Nutr Cancer 2001;40(2):87-91.
  27. Blank MM, Wentzensen N, Murphy MA, et al. Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study. Br J Cancer 2012;106(3):596-602.
  28. Genkinger JM, Hunter DJ, Spiegelman D, et al. A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer. Cancer Causes Control 2006;17(3):273-85.
  29. Koushik A, Hunter DJ, Spiegelman D, et al. Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev 2005; 14(9):2160-7.
  30. Zeng ST, Guo L, Liu SK, et al. Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies. Clin Nutr 2014 pii: S0261-5614(14)00185-X.
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Cancer Statistics Explained

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