Reproductive, menstrual, and other hormone‐related factors and risk of renal cell cancer

Abstract

A role of hormone-related factors in renal cell cancer (RCC) etiology has been hypothesized, but the epidemiological evidence is inconsistent. The present study aimed at evaluating the effect of reproductive, menstrual and other gender-specific variables on RCC risk among women. This study is part of a larger hospitalbased, case-control study on RCC risk, conducted in northern, central and southern Italy. Cases were 273 women, below age 80, with histologically confirmed, incident RCC. Controls were 546 women hospitalized for acute, nonneoplastic conditions, frequency-matched to cases by age and center. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression models. RCC risk was inversely related to age at first birth (OR 5 0.7, 95% CI 0.5-1.0, for ≥25 years vs. <25 years). Hysterectomy was found to double RCC risk (OR 5 2.3, 95% CI 1.3-4.2). A negative association of borderline-statistical significance emerged for age at menarche, whereas, no associations were found between RCC risk and parity, menopausal status, age at menopause and use of hormone replacement therapy or oral contraceptives. Our findings give support to a role of hysterectomy in increasing RCC risk without corroborating, however, a major role of female hormone-related factors. ' 2008 Wiley-Liss, Inc.Key words: kidney cancer; reproductive and menstrual factors; hormones; hysterectomy; case-control study The kidney is among the 10 most common cancer sites in more developed countries. Worldwide, incidence rates are lower in women than in men, with 1:2 ratio. Such difference is recorded in Italy also, where the world-standardized incidence rates per 100,000 person-years are 11.5 and 4.6 among men and women, respectively. 1 Cigarette smoking, obesity and hypertension are the only established risk factors for renal cell cancer (RCC) (i.e., the most common type of kidney cancer) in both sexes. 2-5 Among potential risk factors, a role of hormone-related dynamics on RCC development has been hypothesized. To our knowledge, human studies have never examined endogenous estrogens with RCC risk. However, steroid hormone receptors have been found in normal and cancerous renal cell tissue, indicating possible hormonal regulations 6 ; this line of reasoning is strengthened by the observation that polymorphisms of the estrogen receptor gene were hypothesized to play a role in the pathogenesis of RCC. 7 Animal studies have shown that estrogens can promote or induce kidney cancer development. 8 In addition, obesity, which is consistently associated to RCC, provides a major source of estrogens in postmenopausal women. 9 To evaluate the role of menstrual and reproductive history, exogenous hormone use, and gynecologic surgery in RCC etiology in women, we conducted a multicentre, case-control study in Italy. Material and methodsThis study is part of a hospital-based, case-control study on RCC risk in both sexes, which has been described in details elsewhere. 10,11 The study was conducted between 1992 and 2004 in 4 Italian a...

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

“…In classic epidemiological studies, it was defined that, for women, ccRCC risk was inversely related to age at first given birth (OR=0.7; for ≥25 vs. <25 years), and that hysterectomies doubled ccRCC risk (OR=2.3). A negative association between ccRCC and age at menarche was also shown, suggesting a link between steroid sex hormones and ccRCC (17). Moreover, high parity was shown to be associated with an increased risk of ccRCC, while oral contraceptive use was associated with a reduced risk.…”

Parity and Kidney Cancer Risk: Evidence from Epidemiologic Studies

“…The number of cases enrolled in these studies ranged from 56 (25) to 608 (21), and the number of control subjects varied from 227 (22) to 5,619 (25). Control subjects were drawn from the general population in 5 studies (13,(21)(22)(23)28), hospitals in 3 studies (16,25,26). The highest parity number varied from 3 (16) to more than 6 (21).…”

“…Four prospective (15,(17)(18)(19)) and 7 case-control studies (13,16,21,22,25,26,28) were included in the doseresponse analysis. The summary relative risk per live birth was 1.08 (95% CI, 1.05-1.10), with none of heterogeneity (Q ¼ 9.34; P ¼ 0.500; I 2 ¼ 0%; Table 2 and Fig.…”

Epidemiologic characteristics and risk factors for renal cell cancer

“…Reductions in risk of renal cell cancer have been reported among users of oral contraceptives in some, 76,148 but not all studies, 149,150 and in the large international case-control study protection was restricted to nonsmokers. 76 Several studies have reported an almost two-fold increased risk among women with high parity compared with nulliparous women, after adjustment for obesity, 76,148,151 and an inverse association between age at fi rst birth and risk of renal cell cancer has been reported in some 28,39,149,151 but not all studies.…”

“…76 Several studies have reported an almost two-fold increased risk among women with high parity compared with nulliparous women, after adjustment for obesity, 76,148,151 and an inverse association between age at fi rst birth and risk of renal cell cancer has been reported in some 28,39,149,151 but not all studies. 148,150 Hormones have induced renal tumors in laboratory animals; however, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited and not entirely consistent to date.…”