May 16, 2011 / 3 notes

Obesity: A Risk Factor for Ovarian and Endometrial Cancer

This is a paper that I had to write for a Women’s Epidemiology class this past spring. I thought I would share it (even though it’s long and potentially boring) due to the fact that so many women have no idea that obesity can be a risk factor for ovarian and endometrial cancer. I hope this will shed some light on the health consequences of obesity that are not widely publicized. 

Introduction

A popular descriptive term coined for the United States is ‘fast food nation’, implying that Americans as a whole consume ‘fast food’ which is broadly characterized as unhealthy, greasy, food of low nutritional value. The consumption of ‘fast food’ may be expanding our wallets with the cash not used on more expensive, albeit more nutritional meals, but it is also expanding our waists as well. Over the past few decades as ‘fast food’ has become more accessible, and Americans have slowly morphed into more sedentary beings, obesity has shown a great increase in prevalence across the country. While obesity is a concern for an individual’s general health, studies have linked obesity specific negative health outcomes and disease such as: coronary heart disease, Type II diabetes, hypertension, sleep apnea, liver/gallbladder disease, along with endometrial, breast, colon, and ovarian cancer.  Endometrial and ovarian cancer are two types of aggressive cancers with high morbidity/mortality rates, and which solely effect women. With the increasing prevalence of obesity, and its link to endometrial and ovarian cancers, obesity continues to grow more threatening in terms of the public health impact on women if it is not mitigated. This paper will describe obesity and how it is associated with both endometrial and ovarian cancer using research articles, and epidemiologic studies to solidify the association.

Obesity

Worldwide, obesity is on the rise, but it is gaining prevalence within the United Sates at an increasingly alarming rate. The obesity epidemic that society is witnessing today has been attributed to the social, economic, and technological advances that have come about over the last decades [8]. In order to be characterized as obese, one needs to have a body mass index (BMI) over 30. An individual’s BMI is calculated from an individual’s weight and height, and is a good predictor of body fat content [5]. This guideline varies slightly between individuals, especially within children, but it is generally a good measurement and is used to determine the healthy weight of an individual. Other measurements that are used to determine if an individual is obese are: waist circumference, calculation of waist-to-hip circumference ratios. Imaging techniques to assess obesity include ultrasounds, and magnetic resonance images (MRIs) [5].

Many studies have looked at the etiology of obesity to determine if an individual is predisposed by a gene to become obese, or if environment plays a major role. The general consensus is that between 30-40% of obesity can be attributed to genetics, while the remaining percentage is attributable to environmental factors [8]. Obesity amplifies the risk for diseases with high morbidity/mortality rates, and it has been shown that the pattern of fat distribution also plays an important role in diseases associated with obesity [8]. It is important to note the difference in disease risk based on adipose tissue distribution due to the fact that the gender of an individual plays an important role in body fat distribution: men generally have abdominal/upper-body obesity, while women are likely to have lower-body fat distribution [8]. 

Over recent decades, obesity has grown in prevalence across both genders within society; however, the National Health and Nutrition Examination Surveys (NHANES) studies have noted that the highest prevalence of obesity was found in women, especially those from minority groups [8]. A recent study conducted in 2002 by the CDC discovered that the frequency of obesity among women stands at more than 35%. Studies that have attempted to identify the age and duration of obesity which is most detrimental have determined that, although short-term obesity can be harmful, long-term obesity increases a women’s risk for a number of cancers such as: endometrial, breast, and ovarian. Ordinarily, although breast cancer is widespread, endometrial and ovarian cancer have not been as common but are witnessing an increased incidence in past decades, which has been attributed to the increase in obesity incidence among women. Women need to have a focused intervention with respects to obesity and cancer because women have a higher mortality rate from cancer when obese compared to men. A prospective study that evaluated 750,000 mean and women after a 12-year follow-up period found that women who were at least 40% overweight were 55% more likely to die from cancer, while men were only 33% more likely [8].

Ovarian Cancer

Today, ovarian cancer is the 8th leading cause of death among women in the world. However, this does not mean that it is also the 8th most common disease in women [5]. In reality, ovarian cancer accounts for 21,880 new cancer diagnoses in 2010, compared to 202,964 new breast cancer diagnoses, and accounts for 13,850 deaths [9]. Surprisingly, this seems contrary to most diseases in that there is an increased prevalence in higher socioeconomic populations, with white women having a higher incidence compared to black women, 13.5 to 10 per 100,000 women respectively [9]. However, while more white women die from ovarian cancer, the mortality rates of white compared to black women are closer than the incidence rates suggesting that there is a healthcare gap and black women aren’t getting the proper care, or are being diagnosed at a later stage when the cancer is less treatable. If diagnosed with ovarian cancer, grim statistics show that the 5-year survival rate is about 37% [7]. 

Like most cancers, it is hypothesized that damage to DNA causes cells to proliferate uninhibited, and because the body cannot repair the damaged DNA, the abnormal cells spread throughout the area causing cancer.  The damage to the DNA could be either genetic or environmental. In the past, researchers have had difficulty pinpointing the exact cause of ovarian cancer, however, there are a number of known risk factors for ovarian cancer. Risk factors for ovarian cancer include: age, family history, menopausal hormone therapy (MHT), and cancer history [3]. Recent studies have also found protective factors for ovarian cancer including parity, and oral contraceptive use.

The association between obesity and ovarian cancer is not as well established as the protective effects of oral contraceptive use. Studies conducted in the past have often found varying evidence to suggest a causal path, with varying degrees of certainty, so it is important that more studies are conducted to confirm the etiology and association of obesity with ovarian cancer. One study conducted using the California Teachers Study cohort, found evidence to suggest a causal pathway. This study followed 56,091 women, and investigated whether hormone therapy and obesity were associated with ovarian cancer risk. Researchers used a Cox proportional hazards regression model with a time-scale of age in order to estimate relative risks and 95% confidence intervals [4]. Authors also adjusted for confounders such as: race/ethnicity, oral contraceptive use (along with duration), parity, wine consumption, physical activity, smoking history, and height [4]. After confounding effects were accounted for researchers found that overall obesity did not increase a women’s risk for ovarian cancer, but that abdominal adiposity and weight gain did. Researchers also saw an increase in risk in those who used hormone therapy for greater than five years, but did not see an increased risk in women who were obese and used hormone therapy [4]. This study helped to solidify the proposed biological mechanism that obesity increases estrogen levels, and it is therefore the estrogen levels that are a risk for ovarian cancer. Unfortunately, there is the potential for some limitations within this study in that researchers used self-reported anthropometric measurements, which could introduce information bias. There were also a small number of cases, which made it difficult for researchers to have enough power to make solid associations, and this study never updated women’s anthropometric measurements over the course of the ten-year study period [4]. Lastly, the confidence intervals within the study often encompassed one, which could mean that no real association was observed, and once again, this could be due to the small sample size of cases.

Another study, conducted by Lietzmann et al, attempted to take a closer look at the association between obesity and ovarian cancer, and was also able to find a positive association putting obesity on the causal pathway for ovarian cancer. This was a prospective cohort, following 94,525 women from 1996 to 2003, and looked specifically at obese women and the use of menopausal hormone therapy (MHT). Researchers looked at menopausal hormone therapy due to the fact that obese women have higher levels of endogenous estrogen, because of the “conversion of adrostenedione to estrone and the aromatization of androgens to estradiol in peripheral adipose tissue”, and women who utilize MHT have higher levels of circulating estrogen [6]. It was expected that MHT nonusers would exhibit a more obvious association between adiposity and obesity, while MHT users would show a weaker association. In this study, researchers wanted to look further into the question about whether or not the main biological mechanism of obesity, causing ovarian cancer, was its effect on hormones and from there determine the etiology of the disease [7].  This study took into consideration MHT use along with family history of ovarian cancer, and divided women into three different BMI groups to determine which group had the highest risk of ovarian cancer and used Cox regression to estimate hazard ratios and 95% confidence intervals; the groups were: normal weight (18.5-24.9 kg/), overweight (25-29.9 kg/, and obese (³30 kg/[7]. After adjusting for age, researchers found that obesity had a positive association with ovarian cancer in normal weight women compared to obese women (RR=1.26; 95% CI, 0.94-1.68), and the association was even greater when comparing normal weight women to obese women (RR=1.38; 95% CI, 0.92-2.09).  However, researchers found there was no association for women who used MHT when comparing obese women to normal weight women, suggesting that the adverse effects of excess body weight on ovarian cancer risk is due to low exposure to exogenous hormones, therefore alluding to estrogen levels as being the biological mechanism that increases risk for ovarian cancer in obese women. Unfortunately, this study also had some limitations in that it used self-reported weight and height, although the correlation between self-reported and researcher measured height/weight was upwards of 0.80, and there was also the chance for misclassification of women into their respective case/control groups since weight/height measurements were reported before the ovarian cancer diagnosis [7]. However, the misclassification of women was nondifferential, which would have attenuated results towards the null, so it can be assumed that the reported results are likely close to an actual representation of there being a positive association.

Endometrial Cancer

Compared to ovarian cancer, endometrial cancer is much more prevalent in that it is the fourth most common cancer in women [6]. Over the past decades, the incidence of ovarian cancer has slowly increased each year, while mortality rates have doubled between 1987 and 1998 [6]. Almost all studies that have looked at the association between obesity and endometrial cancer have unanimously concluded that there is a strong positive association, with as much as a 3-fold increase in risk of endometrial cancer among morbidly obese women [2]. Estimates suggest that about 90% of “Type 1 endometrial cancer patients are obese”; compared to women with breast cancer, this is almost double the percentage. Currently, the strongest biological mechanism that links obesity to endometrial cancer involves the ‘metabolic and endocrine effects of obesity’ and the induced alterations in the production of the peptide and steroid hormones [6].

One study that looked at the effects of obesity on endometrial cancer was conducted using a case-control study design, and included 168 cases and 384 controls; this study attempted to “distinguish between the independent effects of the amount of body fat and it’s distribution on [endometrial cancer] risk” [2]. Researchers used an exposure odds ratio as an estimate of the relative risk using an unconditional logistic regression. The final result of the study supported previous studies that evidenced an increase in risk among obese women for endometrial cancer, and found that excess risk is associated and confined mostly to morbidly obese women. A strength of this study was that all anthropometric measurements were taken by a certified dietician, so women were unable to misclassify themselves into a lower weight group, but there could potentially be an introduction of bias in that subjects were interviewed about their reproductive history, medical history, and other background information including lifestyle which was not confirmed using medical charts, or any other confirmation technique. It is likely that these results hold value in the association that was measured, however, due to the non-diverse population of its participants (Cases: White: 153, Black: 15; controls: White: 312 Black: 21 Asian: 1) it could not be generalized to Black or Asian women.  

While many women who are diagnosed with endometrial or ovarian cancer may be genetically predisposed, which is not a modifiable trait, there are many ways for a woman to reduce her risk by behaviors associated with increased risks. A meta-analysis of different studies have concluded that the most significant risk factors for endometrial cancer are: unopposed estrogen, sedentary lifestyle and obesity; of these risk factors, all are modifiable [6]. Due to the fact that obesity has also been positively associated with ovarian cancer, and oral contraceptive use has been shown to have a protective effect, these women can also modify their behaviors to decrease their risk. It has been estimated that the use of combination oral contraceptives could potentially prevent almost 2,000 endometrial cancer diagnoses each year [6]. Unfortunately, there is inadequate evidence to point in the direction that weight loss alone will reduce a women’s risk for endometrial or ovarian cancer, but many studies have suggested that baseline recreational physical activity can reduce a women’s risk by up to 33%, and that profound weight loss caused by bariatric surgery can help reduce cancer risk in morbidly obese women [6]. Research has not been conducted yet to determine whether profound weight-loss through exercise could also have the decreased risk like bariatric surgery, however, it can be assumed that it would based on the continually documented health benefits of fitness in preventing disease, especially those associated with obesity.

Conclusion

Obesity is an increasing public health threat as it is causally associated with the morbidity/mortality of many different cancers and diseases (e.g. Type II diabetes), and because it decreases an individual’s quality of life, and survival rates after operations [6]. It is important to further explore the associations between obesity and different types of diseases within women due to growing gap between men and women that have shown women to have a higher incidence of obesity. It is also important to alert women to the known associations between obesity and diseases such as endometrial cancer because unfortunately, the majority of women outside of the healthcare sphere do not know that obesity can increase their risks for less well-known diseases. It can be postulated that knowledge of the higher risks for serious, life-threatening cancers with high mortality rates, and an increased risk of perioperative morbidity, could encourage women to choose healthier lifestyles to combat these obesity-associated cancer, and make easy behavior modifications, like increasing physical activity and healthier nutritional habits, in order to help fight obesity. 

References

1.     Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I 

 

(2005) Endometrial cancer. The Lancet 366: 491-505

2.     Austin H, Austin JM, Edward EP, Hatch KD, Shingleton MH (1991) Endometrial cancer, obesity, and body fat distribution. Cancer Research 51: 568-572

3.     Butler C (2009) Obesity and ovarian cancer: What’s the link? American Fitness: 62-63.

4.     Canchola, AJ, Chang ET, Bernstein L et al. (2010). Body size and the risk of ovarian cancer by hormone therapy use in the California teachers study cohort. Cancer Causes Control 21: 2241-2248

5.     Division of Cancer Prevention and Control (2010). CDC – Gynecological 

 

cancers. Retrieved from Center for Disease Control and Prevention website: 

 

http://www.cdc.gov/cancer/gynecologic

6.     Fader AN, Arriba LN, Frasure HE, von Gruenigen VE (2009) Endometrial 

 

cancer and obesity: Epidemiology, biomarkers, prevention, and survivorship. 

 

Gynecologic Oncology 114: 121-127

7.     Leitzmann MF, Koebnick C, Danforth KN, Brinton LA, Moore SC, Hollenbeck AR, Schatzkin A, Lacey JV (2009). Body mass index and risk of ovarian cancer. Cancer: 812-822. doi: 10.1002/cncr.24086

8.     Pi-Sunyer FX (2002) The obesity epidemic: Pathophysiology and 

 

consequences of obesity. Obesity Research 10: 97S-104S

9.     National Cancer Institute (2006) What you need to know about: Ovarian cancer. Retrieved from National Cancer Institute at the National Institutes of Health website: http://www.cancer.gov/cancertopics/wyntk/ovary

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