Endometriosis linked to increased risk for melanoma

Endometriosis Linked to Increased Risk for Melanoma
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
Authors and Disclosures
CME/CE Released: 10/30/2007; Valid for credit through 10/30/2008

October 30, 2007 — Endometriosis increased the risk for melanoma, according to the results of a large, prospective French cohort study reported in the October 22 issue of the Archives of Internal Medicine.

“An association between melanoma and endometriosis has been reported, but most findings relied on case-control studies or a limited number of melanoma cases, and therefore the available evidence is weak,” write Marina Kvaskoff, MPH, from Institut National de la Santé et de la Recherche Médicale and Institut Gustave Roussy in Villejuif, France, and colleagues. “Moreover, the effect of other benign gynecological diseases on melanoma risk is unknown.”

The Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale cohort includes 98,995 French women, insured by a national health scheme mostly covering teachers, who were aged 40 to 65 years at enrollment. Beginning in 1990, the investigators regularly collected data on history of endometriosis and other benign gynecologic diseases, and they calculated relative risks (RRs) using Cox proportional hazards regression models.

Of 91,965 women followed up for 12 years, 5949 had a history of endometriosis, and 363 were diagnosed with melanoma during follow-up. History of endometriosis was a significant risk factor for development of melanoma (RR, 1.62; 95% confidence interval [CI], 1.15 – 2.29).

Women with a history of fibroma (n = 24,375) also had a significantly increased risk for melanoma vs those with no such history (RR, 1.33; 95% CI, 1.06 – 1.67). However, ovarian cysts, uterine polyps, breast adenoma/fibroadenoma, and breast fibrocystic disease were not significant predictors of melanoma.

“These data provide the strongest evidence to date of a positive association between a history of endometriosis and melanoma risk,” the study authors write. “The association between fibroma and melanoma, which has not been previously described, warrants further investigation.”

Limitations of the study include possible misclassification bias, lack of data on specific types of drugs used as hormonal treatment for the studied gynecologic conditions, study cohort being predominantly female teachers with high levels of education and socioeconomic status, lack of data on sun exposure and sunburn history, and possible unknown residual confounders.

“Endometriosis is an important women’s health issue worldwide,” the study authors conclude. “Because this disease appears to be a risk indicator for cutaneous melanoma, gynecologists may play a role in melanoma prevention by alerting patients with endometriosis of their higher susceptibility to the disease.”

The French League Against Cancer, the European Community, the 3M Company, the Mutuelle Générale de l’Education Nationale, the Institut Gustave Roussy, the Institut National de la Santé et de la Recherche Médicale, and the Fondation de France supported this study. Some of the study authors have disclosed relevant financial relationships.

Arch Intern Med. 2007;167:2061-2065.

Clinical Context

An unexpected association has been found between melanoma and a history of endometriosis in 3 previous cohort studies, and a retrospective cohort study of women with infertility found an increased risk for melanoma. Some reproductive factors may be associated with both endometriosis and melanoma because nulliparity and pauciparity have been associated with melanoma, and the risk for melanoma has been observed to be lower among women with high parity and earlier age at first pregnancy.

This is a prospective cohort study of French women in a national health insurance scheme who were followed up for nearly 12 years to examine the association between benign gynecologic conditions and the risk for melanoma.

Study Highlights

• Included were 98,995 women aged 40 to 65 years at baseline, who were primarily teachers covered by a national health insurance scheme, were enrolled for a 2-year period, and who completed a baseline questionnaire.
• Excluded were women with a preexisting cancer (except basal cell carcinoma), those lost to follow-up, and those who had never menstruated.
• Women completed follow-up questionnaires every 2 years, which addressed medical events including cancer and benign gynecologic diseases.
• Information on age at menarche, parity, body mass index (BMI), duration of menstrual cycles, and infertility treatments were obtained.
• Benign gynecologic diseases were defined as those treated or diagnosed via a specific diagnostic procedure; for all conditions, type of treatment was described.
• A positive exposure of a benign gynecologic condition included conditions diagnosed by laparoscopy, biopsy, hysterography, hysteroscopy, or ultrasonography.
• Ovarian cysts occurring with endometriosis were not separately considered.
• Cox proportional hazard regression models were used to derive RRs.
• During follow-up, a total of 363 melanoma cases were ascertained among 91,965 women, and pathology reports were available for 97.8% of melanoma cases.
• Median follow-up was 12 years.
• 84% of women had a BMI at baseline of 25 kg/m 2 or less, 60% had chestnut-colored hair, 18% were blond, and 13% had brown hair.
• 38% were highly sensitive to sun exposure, and 46% were moderately sensitive to sun exposure.
• 24% had very many nevi and 9% had very many freckles.
• Women with melanoma were significantly more likely to have blond, red, or chestnut hair, as expected, and a high sensitivity to sun exposure with a larger number of freckles and nevi.
• Educational level and BMI were not correlated with melanoma risk.
• A personal history of endometriosis (n = 5949) was associated with an increased risk for melanoma (RR, 1.62; 95% CI, 1.15 – 2.29).
• A significantly increased risk for melanoma was found for women with a personal history of uterine fibroma (n = 24,375) vs those with no such history (RR, 1.33; 95% CI, 1.06 – 1.67).
• A history of ovarian cysts, uterine polyps, breast adenoma/fibroadenoma, or breast fibrocystic disease was not significantly associated with melanoma risk.
• Adjustment for infertility treatment, progestagen use, hormone use, parity, and menopausal status did not change the results.
• There was a significant association between endometriosis and red hair ( P = .02).
• The association between red hair and endometriosis and melanoma risk was not significant.
• In this cohort, nulliparity was not associated with melanoma risk.
• The authors concluded that this prospective study provided strong evidence of a link between a personal history of endometriosis and cutaneous melanoma.

Pearls for Practice

• A personal history of endometriosis or uterine fibroma is associated with higher risk for cutaneous melanoma in women.
• A history of ovarian cysts, uterine polyps, breast adenoma/fibroadenoma, or breast fibrocystic disease is not significantly associated with melanoma risk.