Ovarian cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Huda A. Karman, M.D.

## Overview

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The risk of developing ovarian cancer appears to be affected by several factors; in fact, early age at first pregnancy, older ages of final pregnancy, and the use of low dose hormonal contraception have been associated with a lower incidence of ovarian cancer. There is good evidence that in some women genetic factors are important.

## Risk Factors

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Common risk factors in the development of ovarian cancer include:[1]

Ovarian cancer risk factors |  Characterestics |  description

|
|

Known risk factors [2][3][4][5][6][7][8][9][10][11][12] | Age | As age increases, ovarian cancer incidence increases.
Hormonal and reproductive factors | Early menarche and late menopause, Nulliparity, Infertility
Early menarche and late menopause | Both increase the frequency of the ovulation and the ovarian epithelium exposure to persistent injury
Nulliparity  | Studies have shown that multiparity and full-term pregnancies decrease the risk of ovarian cancer and fallopian tubal carcinoma
Infertility | Infertility is an independent risk factor of ovarian cancer
Endometriosis  | Ovarian cancers that arise from endometriotic tissue usually affect young women and have better prognosis and survival rates
Polycystic ovarian syndrome | The association is controversial and complex
Postmenopausal hormone therapy | Estrogen therapy alone has more association with ovarian cancer than combined estrogen-progesteron therapy
Intrauterine device | Regardless of the type of the IUD, studies have shown an increased risk of ovarian cancer with IUD use
Genetic factors |
BRCA gene mutations | The risk is more with BRCA1 carriers than BRCA2 carriers. Ovarian cancer develops at an earlier age in BRCA1-carrier women compared to BRCA2-carrier women. Serous adenocarcinoma is the most common type.General women and women with BRCA mutations usually present with stage III or IV
Lynch syndrome | Hereditary nonpolyposis colorectal cancer (HNPCC) : 1 percent of cases with ovarian cancer have Lynch syndrome.
Other genetic factors | The genes in the Fanconi anemias pathway can undergo different mutations and lead to the development of ovarian and/or breast cancer. The genes that are associated with ovarian cancer are: BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, PALB2, and BARD1
Family history of certain cancers | BRCA mutation carriers with personal or family history of breast cancer have higher risk of developing ovarian cancer that those without BRCA mutation
Personal history of breast cancer | Increases the risk of breast-ovarian syndrome
Environmental factors | Cigarette smoking associated with mucinous ovarian cancer, asbestos,Talc (Its association is controversial).
Other factors | Diet: dairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association, exercise: No clear evidence about the association between physical activity and breast cancer, and obesity: can increases the risk of ovarian cancer and the risk of its mortality, Pelvic inflammatory disease can increase the risk of and might be used as tumor marker for ovarian tumor.
Possible risk factors[12][9] | Obesity | Can increases the risk of ovarian cancer and the risk of its mortality.
Talc use on genetals | Its association is controversial).
Unknown risk factors[10][13] | Food types and amount | Dairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association
Fertility drugs | The role of medications used for ovulation induction in increasing the risks of ovarian cancer is controversial. The association between the fertility drugs and ovarian cancer could be due to the stimulating effect of these drug, however this association is not a causal relation
Sedentary life | Its association is unknown

* Common risk factors in the development of ovarian cancer include:
* Age:
* There is a proportional association between age and ovarian cancer, as age increases, ovarian cancer incidence increases.[14]
* Hormonal and reproductive factors:
* Early menarche and late menopause:
* Both increase the frequency of the ovulation and the ovarian epithelium exposure to persistent injury.[14][15]
* Nulliparity
* Studies have shown that multiparity and full term pregnancies decrease the risk of ovarian cancer and fallopian tubal carcinoma.[16][17]
* Infertility:
* Type of infertility and its causes should be taken in consideration as different causes can increase the risk of ovarian cancer such as:[18]
* Primary infertility
* Secondary infertility as endometriosis
* The role of medications used for ovulation induction in increasing the risks of ovarian cancer is controversial. The association between the fertility drugs and ovarian cancer could be due to the stimulating effect of these drug, however this association is not a causal relation.[13]
* Regardless to the fertility medications use, infertility is an independent risk factor of ovarian cancer.[13]
* Endometriosis
* Ovarian cancers that arise from endometriotic tissue usually affect young women and have better prognosis and survival rates.[19]
* Polycystic ovarian syndrome:
* The association is controversial and complex. Meta-analysis found an association between PCOS and endometrial cancer in general but not with ovarian cancer specifically.[20]
* Postmenopausal hormone therapy:
* A non statistical significant association found between combined estrogen-progesteron therapy and ovarian carcinoma.[21]
* Meta-analysis found small significant association between ovarian cancer and estrogen therapy alone.[22]
* Intrauterine device:
* Regardless of the type of the IUD, studies have shown an increased risk of ovarian cancer with IUD use.[23]
* Genetic factors
* BRCA gene mutations: the risk of both ovarian and breast cancers increases in women with BRCA mutations.
* The risk is more with BRCA1 carriers than BRCA2 carriers.[3]
* Ovarian cancer develops at an earlier age in BRCA1-carrier women compared to BRCA2-carrier women. Serous adenocarcinoma is the most common type.[4]
* General women and women with BRCA mutations usually present with stage III or IV.[24]
* However, the grade is higher in women who are BRCA mutations' carries.[25]
* The short-term survival rate of ovarian cancer in women with BRCA mutations is higher than non-carriers.[26]
* Prophylactic bilateral salpingo-oophorectomy can be done in BRCA mutation carries who are at higher risk of developing fallopian tube cancer and primary peritoneal carcinoma.[27]
* Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) :
* 1 percent of cases with ovarian cancer have Lynch syndrome.[5]
* Family history of breast cancer:
* It is not clear whether the family’s pattern of cancer is due to chance, shared lifestyle factors, a genetic risk passed from parents to children or a combination of these factors.
* By American cancer society, about 5 to 10% of ovarian cancers are a part of family cancer syndromes resulting from inherited changes (mutations) in certain genes.
* BRCA mutation carriers with personal or family history of breast cancer have higher risk of developing ovarian cancer that those without BRCA mutation[28]
* Other genetic factors:
* The genes in the Fanconi anemias pathway can undergo different mutations and lead to the development of ovarian and/or breast cancer[6]. The genes that are associated with ovarian cancer are: BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, PALB2, and BARD1[7]
* Environmental factors such as:
* Cigarette smoking associated with mucinous ovarian cancer[8]
* Asbestos,Talc (Its association is controversial)[9]
* Other factors such as:
* Diet:
* Ddairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association.[10]
* Exercise:
* No clear evidence about the association between physical activity and breast cancer.[11]
* Obesity:
* Can increases the risk of ovarian cancer and the risk of its mortality.[12]
* Pelvic inflammatory disease can increase the risk of and might be used as tumor marker for ovarian tumor[29]

## References

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1. ↑ A. Daniilidis & V. Karagiannis (2007). "Epithelial ovarian cancer. Risk factors, screening and the role of prophylactic oophorectomy". Hippokratia. 11 (2): 63–66. PMID 19582179. Unknown parameter `|month=` ignored (help)
2. ↑ . doi:10.22034/APJCP.2017.18.1.11. Missing or empty `|title=` (help)
3. ↑ 3.0 3.1 Chen S, Parmigiani G (2007). "Meta-analysis of BRCA1 and BRCA2 penetrance". J Clin Oncol. 25 (11): 1329–33. doi:10.1200/JCO.2006.09.1066. PMC 2267287. PMID 17416853.
4. ↑ 4.0 4.1 Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H; et al. (2005). "BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases". Cancer. 104 (12): 2807–16. doi:10.1002/cncr.21536. PMID 16284991.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
5. ↑ 5.0 5.1 Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR; et al. (1998). "BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing". Am J Obstet Gynecol. 178 (4): 670–7. doi:10.1016/s0002-9378(98)70476-4. PMID 9579428.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
6. ↑ 6.0 6.1 Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA; et al. (2011). "Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer". Gynecol Oncol. 121 (2): 353–7. doi:10.1016/j.ygyno.2011.01.020. PMID 21324516.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
7. ↑ 7.0 7.1 Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S; et al. (2016). "Inherited Mutations in Women With Ovarian Carcinoma". JAMA Oncol. 2 (4): 482–90. doi:10.1001/jamaoncol.2015.5495. PMC 4845939. PMID 26720728.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
8. ↑ 8.0 8.1 Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM (2006). "Does smoking increase risk of ovarian cancer? A systematic review". Gynecol Oncol. 103 (3): 1122–9. doi:10.1016/j.ygyno.2006.08.012. PMID 17005245.CS1 maint: Multiple names: authors list (link)
9. ↑ 9.0 9.1 9.2 Huncharek M, Geschwind JF, Kupelnick B (2003). "Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies". Anticancer Res. 23 (2C): 1955–60. PMID 12820486.CS1 maint: Multiple names: authors list (link)
10. ↑ 10.0 10.1 10.2 Blank MM, Wentzensen N, Murphy MA, Hollenbeck A, Park Y (2012). "Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study". Br J Cancer. 106 (3): 596–602. doi:10.1038/bjc.2011.572. PMC 3273348. PMID 22223086.CS1 maint: Multiple names: authors list (link)
11. ↑ 11.0 11.1 Carnide N, Kreiger N, Cotterchio M (2009). "Association between frequency and intensity of recreational physical activity and epithelial ovarian cancer risk by age period". Eur J Cancer Prev. 18 (4): 322–30. doi:10.1097/CEJ.0b013e32832bf3fa. PMID 19390450.CS1 maint: Multiple names: authors list (link)
12. ↑ 12.0 12.1 12.2 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". N Engl J Med. 348 (17): 1625–38. doi:10.1056/NEJMoa021423. PMID 12711737.CS1 maint: Multiple names: authors list (link)
13. ↑ 13.0 13.1 13.2 Bristow RE, Karlan BY (1996). "Ovulation induction, infertility, and ovarian cancer risk". Fertil Steril. 66 (4): 499–507. PMID 8816606.
14. ↑ 14.0 14.1 Gates MA, Rosner BA, Hecht JL, Tworoger SS (2010). "Risk factors for epithelial ovarian cancer by histologic subtype". Am J Epidemiol. 171 (1): 45–53. doi:10.1093/aje/kwp314. PMC 2796984. PMID 19910378.CS1 maint: Multiple names: authors list (link)
15. ↑ Tsilidis KK, Allen NE, Key TJ, Dossus L, Lukanova A, Bakken K; et al. (2011). "Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition". Br J Cancer. 105 (9): 1436–42. doi:10.1038/bjc.2011.371. PMC 3241548. PMID 21915124.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
16. ↑ Stewart LM, Holman CD, Aboagye-Sarfo P, Finn JC, Preen DB, Hart R (2013). "In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk". Gynecol Oncol. 128 (2): 260–4. doi:10.1016/j.ygyno.2012.10.023. PMID 23116937.CS1 maint: Multiple names: authors list (link)
17. ↑ Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER (2001). "Menstrual and reproductive factors in relation to ovarian cancer risk". Br J Cancer. 84 (5): 714–21. doi:10.1054/bjoc.2000.1596. PMC 2363792. PMID 11237375.CS1 maint: Multiple names: authors list (link)
18. ↑ Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE; et al. (2004). "Ovarian cancer risk associated with varying causes of infertility". Fertil Steril. 82 (2): 405–14. doi:10.1016/j.fertnstert.2004.02.109. PMID 15302291.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
19. ↑ Erzen M, Rakar S, Klancnik B, Syrjänen K, Klancar B (2001). "Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study". Gynecol Oncol. 83 (1): 100–8. doi:10.1006/gyno.2001.6382. PMID 11585420.CS1 maint: Multiple names: authors list (link)
20. ↑ Barry JA, Azizia MM, Hardiman PJ (2014). "Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis". Hum Reprod Update. 20 (5): 748–58. doi:10.1093/humupd/dmu012. PMC 4326303. PMID 24688118.CS1 maint: Multiple names: authors list (link)
21. ↑ Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M; et al. (2003). "Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial". JAMA. 290 (13): 1739–48. doi:10.1001/jama.290.13.1739. PMID 14519708.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
22. ↑ Zhou B, Sun Q, Cong R, Gu H, Tang N, Yang L; et al. (2008). "Hormone replacement therapy and ovarian cancer risk: a meta-analysis". Gynecol Oncol. 108 (3): 641–51. doi:10.1016/j.ygyno.2007.12.003. PMID 18221779.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
23. ↑ Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE (2007). "Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk". Am J Epidemiol. 166 (8): 894–901. doi:10.1093/aje/kwm157. PMID 17656616.CS1 maint: Multiple names: authors list (link)
24. ↑ Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H; et al. (2005). "BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases". Cancer. 104 (12): 2807–16. doi:10.1002/cncr.21536. PMID 16284991.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
25. ↑ Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S; et al. (2004). "Pathology of ovarian cancers in BRCA1 and BRCA2 carriers". Clin Cancer Res. 10 (7): 2473–81. PMID 15073127.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
26. ↑ Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY; et al. (2012). "Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer". JAMA. 307 (4): 382–90. doi:10.1001/jama.2012.20. PMC 3727895. PMID 22274685.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
27. ↑ Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F; et al. (2003). "Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations". J Clin Oncol. 21 (22): 4222–7. doi:10.1200/JCO.2003.04.131. PMID 14615451.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
28. ↑ Kauff ND, Mitra N, Robson ME, Hurley KE, Chuai S, Goldfrank D; et al. (2005). "Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families". J Natl Cancer Inst. 97 (18): 1382–4. doi:10.1093/jnci/dji281. PMID 16174860.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
29. ↑ Lin HW, Tu YY, Lin SY, Su WJ, Lin WL, Lin WZ; et al. (2011). "Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study". Lancet Oncol. 12 (9): 900–4. doi:10.1016/S1470-2045(11)70165-6. PMID 21835693.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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