Abstract
Purpose
The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology.
Methods
We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model.
Results
Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose–response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer.
Conclusions
Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90
Karim-Kos HE, de Vries E, Soerjomataram I et al (2008) Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 44(10):1345–1389
Jordan SJ, Whiteman DC, Purdie DM et al (2006) Does smoking increase risk of ovarian cancer? A systematic review. Gynecol Oncol 103(3):1122–1129
Gates MA, Rosner BA, Hecht JL et al (2010) Risk factors for epithelial ovarian cancer by histologic subtype. Am J Epidemiol 171(1):45–53
Gram IT, Lukanova A, Brill I et al (2012) Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study. Int J Cancer 130(9):2204–2210
Terry PD, Miller AB, Jones JG et al (2003) Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study. Eur J Cancer 39(8):1157–1164
Tworoger SS, Gertig DM, Gates MA et al (2008) Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer 112(5):1169–1177
Green A, Purdie D, Bain C et al (2001) Cigarette smoking and risk of epithelial ovarian cancer (Australia). Cancer Causes Control 12(8):713–719
Huusom LD, Frederiksen K, Hogdall EV et al (2006) Association of reproductive factors, oral contraceptive use and selected lifestyle factors with the risk of ovarian borderline tumors: a Danish case-control study. Cancer Causes Control 17(6):821–829
Jordan SJ, Green AC, Whiteman DC et al (2007) Risk factors for benign, borderline and invasive mucinous ovarian tumors: epidemiological evidence of a neoplastic continuum? Gynecol Oncol 107(2):223–230
Marchbanks PA, Wilson H, Bastos E et al (2000) Cigarette smoking and epithelial ovarian cancer by histologic type. Obstet Gynecol 95(2):255–260
Modugno F, Ness RB, Cottreau CM (2002) Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer. Epidemiology 13(4):467–471
Pan SY, Ugnat AM, Mao Y et al (2004) Association of cigarette smoking with the risk of ovarian cancer. Int J Cancer 111(1):124–130
Riman T, Dickman PW, Nilsson S et al (2001) Risk factors for epithelial borderline ovarian tumors: results of a Swedish case-control study. Gynecol Oncol 83(3):575–585
Rossing MA, Cushing-Haugen KL, Wicklund KG et al (2008) Cigarette smoking and risk of epithelial ovarian cancer. Cancer Causes Control 19(4):413–420
Soegaard M, Jensen A, Hogdall E et al (2007) Different risk factor profiles for mucinous and nonmucinous ovarian cancer: results from the Danish MALOVA study. Cancer Epidemiol Biomarkers Prev 16(6):1160–1166
Zhang Y, Coogan PF, Palmer JR et al (2004) Cigarette smoking and increased risk of mucinous epithelial ovarian cancer. Am J Epidemiol 159(2):133–139
Kurian AW, Balise RR, McGuire V et al (2005) Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol Oncol 96(2):520–530
Gram IT, Braaten T, Adami HO et al (2008) Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer. Int J Cancer 122(3):647–652
Goodman MT, Tung KH (2003) Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States). Cancer Causes Control 14(6):569–577
Kuper H, Titus-Ernstoff L, Harlow BL et al (2000) Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. Int J Cancer 88(2):313–318
Collaborative Group on Epidemiological Studies of Ovarian Cancer (2012) Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies. Lancet Oncol 13(9):946–956
Ramus SJ, Vierkant RA, Johnatty SE et al (2008) Consortium analysis of 7 candidate SNPs for ovarian cancer. Int J Cancer 123(2):380–388
Merritt MA, Green AC, Nagle CM et al (2008) Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. Int J Cancer 122(1):170–176
Risch HA, Bale AE, Beck PA et al (2006) PGR +331 A/G and increased risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 15(9):1738–1741
Rossing MA, Cushing-Haugen KL, Wicklund KG et al (2007) Menopausal hormone therapy and risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 16(12):2548–2556
Royar J, Becher H, Chang-Claude J (2001) Low-dose oral contraceptives: protective effect on ovarian cancer risk. Int J Cancer 95(6):370–374
Ness RB, Dodge RC, Edwards RP et al (2011) Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer. Ann Epidemiol 21(3):188–196
Glud E, Kjaer SK, Thomsen BL et al (2004) Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer. Arch Intern Med 164(20):2253–2259
Kelemen LE, Sellers TA, Schildkraut JM et al (2008) Genetic variation in the one-carbon transfer pathway and ovarian cancer risk. Cancer Res 68(7):2498–2506
Schildkraut JM, Iversen ES, Wilson MA et al (2010) Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer. PLoS One 5(4):e10061
Terry KL, De Vivo I, Titus-Ernstoff L et al (2005) Androgen receptor cytosine, adenine, guanine repeats, and haplotypes in relation to ovarian cancer risk. Cancer Res 65(13):5974–5981
Bandera EV, King M, Chandran U et al (2011) Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study. BMC Womens Health 11:40
Garcia-Closas M, Brinton LA, Lissowska J et al (2007) Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study. BMC Cancer 7:60
Song H, Ramus SJ, Quaye L et al (2006) Common variants in mismatch repair genes and risk of invasive ovarian cancer. Carcinogenesis 27(11):2235–2242
McGuire V, Felberg A, Mills M et al (2004) Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations. Am J Epidemiol 160(7):613–618
Pal T, Permuth-Wey J, Betts JA et al (2005) BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 104(12):2807–2816
Narod SA, Risch H, Moslehi R et al (1998) Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 339(7):424–428
Balogun N, Gentry-Maharaj A, Wozniak EL et al (2011) Recruitment of newly diagnosed ovarian cancer patients proved challenging in a multicentre biobanking study. J Clin Epidemiol 64(5):525–530
Goodman MT, Lurie G, Thompson PJ et al (2008) Association of two common single-nucleotide polymorphisms in the CYP19A1 locus and ovarian cancer risk. Endocr Relat Cancer 15(4):1055–1060
Goode EL, Chenevix-Trench G, Song H et al (2010) A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet 42(10):874–879
Pike MC, Pearce CL, Peters R et al (2004) Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 82(1):186–195
Wu AH, Pearce CL, Tseng CC et al (2009) Markers of inflammation and risk of ovarian cancer in Los Angeles County. Int J Cancer 124:1409–1415
Risch HA, Jain M, Marrett LD et al (1994) Dietary fat intake and risk of epithelial ovarian cancer. J Natl Cancer Inst 86(18):1409–1415
Baker JA, Odunuga OO, Rodabaugh KJ et al (2006) Active and passive smoking and risk of ovarian cancer. Int J Gynecol Cancer 16(Suppl 1):211–218
Stukel TA, Demidenko E, Dykes J et al (2001) Two-stage methods for the analysis of pooled data. Stat Med 20(14):2115–2130
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188
Leffondré K, Abrahamowitz M, Siemiatycki J et al (2002) Modeling smoking history: a comparison of different approaches. Am J Epidemiol 156:813–823
Massey F Jr (1951) The Kolmogorov-Smirnov test for goodness of fit. J Am Stat Assoc 46(253):68–78
Gilks CB, Ionescu DN, Kalloger SE et al (2008) Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 39(8):1239–1251
R: A Language and Environment for Statistical Computing (2011) R Foundation for Statistical Computing, Vienna, Austria
Kotsopoulos J, Baer HJ, Tworoger SS (2010) Anthropometric measures and risk of epithelial ovarian cancer: results from the nurses’ health study. Obesity (Silver Spring) 18(8):1625–1631
Eriksen M, Mackay J, Ross H (2012) The tobacco atlas. American Cancer Society, Atlanta
Riman T, Dickman PW, Nilsson S et al (2004) Some life-style factors and the risk of invasive epithelial ovarian cancer in Swedish women. Eur J Epidemiol 19(11):1011–1019
Nagle CM, Olsen CM, Webb PM et al (2008) Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. Eur J Cancer 44(16):2477–2484
Chen KM, Zhang SM, Aliaga C et al (2012) Induction of ovarian cancer and DNA adducts by Dibenzo[a, l]pyrene in the mouse. Chem Res Toxicol 25(2):374–380
Zenzes MT, Puy LA, Bielecki R (1998) Immunodetection of benzo[a]pyrene adducts in ovarian cells of women exposed to cigarette smoke. Mol Hum Reprod 4(2):159–165
Risch HA, Marrett LD, Jain M et al (1996) Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case-control study. Am J Epidemiol 144(4):363–372
Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40(9):1213–1223
Plummer M, Herrero R, Franceschi S et al (2003) Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control 14(9):805–814
Slattery ML, Potter JD, Friedman GD et al (1997) Tobacco use and colon cancer. Int J Cancer 70(3):259–264
Lindemann K, Vatten LJ, Ellstrom-Engh M et al (2008) Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study. Br J Cancer 98(9):1582–1585
Kurman RJ, Shih I (2010) The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 34(3):433–443
Pandeya N, Williams GM, Green AC et al (2009) Do low control response rates always affect the findings? Assessments of smoking and obesity in two Australian case-control studies of cancer. Aust N Z Public Health 33:312–319
Greenland S, O’Rourke K (2008) Meta-analysis. In: Rothman KJ, Greenland S, Lash T (eds) Modern epidemiology, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, pp 652–682
Acknowledgments
The work was supported by the European Commission’s Seventh Framework Programme grant agreement no. 223175 (HEALTH-F2-2009-223175). It was also supported by the National Institutes of Health (R01 CA074850, and R01 CA080742 [CON], R01 CA112523, and R01 CA87538 [DOV], R01 CA58598, N01 CN55424, and N01 PC67001 [HAW], R01 CA95023 [HOP], R01 CA61107 [MAL], R01 CA122443, and P50 CA136393 [MAY], R01 CA76016 [NCO], R01 CA54419, and P50 CA105009 [NEC], K07 CA095666, R01 CA83918, and K22 CA138563 [NJO], U01 CA71966, R01 CA16056, K07 CA143047, and U01 CA69417 [STA], R01 CA106414 [TBO], R01 CA063682, R01 CA063678, and R01 CA080978 [TOR], CA 8860, CA92044, and PSA 042205 [UCI], CA17054, CA14089, CA61132, and N01-PC-67010 [USC]); Danish Cancer Society (94 222 52 [MAL]); Mermaid 1 (MAL); German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB9401 (GER); German Cancer Research Center (GER); U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729 [AUS]); National Health & Medical Research Council of Australia (AUS); Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania (AUS); Cancer Foundation of Western Australia (AUS); National Health and Medical Research Council of Australia (199600 [AUS]); Department of Defense (DAMD17-02-1-0669 [HOP], DAMD17-02-1-0666 [NCO], W81XWH-10-1-02802 [NEC], and DAMD17-98-1-8659 [TBO]); The Cancer Institute of New Jersey (NJO); Radboud University Nijmegen Medical Centre (NTH); Intramural Research Program of the National Cancer Institute (POL); Roswell Park Alliance Foundation (RPI); Cancer Research UK (C490/A10119, and C490/A10124 [SEA]); National Health Research and Development Program of Health and Welfare Canada (6613-1415-53 [SON]); American Cancer Society (CRTG-00-196-01-CCE [TBO]); Celma Mastery Ovarian Cancer Foundation (TBO); Lon V Smith Foundation (LVS-39420 [UCI]); Cancer Research UK (UKO, SEA); Eve Appeal (UKO); OAK Foundation (UKO); California Cancer Research Program (00-01389V-20170, R03 CA113148, R03 CA115195, and N01 CN25403 [USC]); California Cancer Research Program (2II0200 [USC]); and National Cancer Institute (P01 CA17054 [USC]). A portion of this work was done at UCLH/UCL within the ‘Women’s Health Theme’ of the NIHR UCLH/UCL Comprehensive Biomedical Research Centre supported by the Department of Health (UKO). The German group thanks Ursula Eilber and Tanja Koehler for competent technical assistance (GER). The Australian group thanks all the clinical and scientific collaborators and the women for their contribution (AUS). The cooperation of the 32 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged (CON). Some data used in the CON study were obtained from the Connecticut Tumor Registry, Connecticut Department of Public Health. The CON study assumes full responsibility for analyses and interpretation of these data. The MALOVA group is grateful to Nick Martinussen for data management assistance (MAL). The NJO group thanks Lorna Rodriguez, Lisa Paddock, and the staff at the New Jersey State Cancer Registry and Thanusha Puvananayagam for their contribution to the study (NJO). The SEARCH group thanks the SEARCH team, Craig Luccarini, Caroline Baynes, and Don Conroy (SEA). The UKOPS group thanks Ian Jacobs, Eva Wozniak, Andy Ryan, Jeremy Ford, and Nyaladzi Balogun for their contribution to the study (UKO).
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Faber, M.T., Kjær, S.K., Dehlendorff, C. et al. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies. Cancer Causes Control 24, 989–1004 (2013). https://doi.org/10.1007/s10552-013-0174-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-013-0174-4