THYROID HORMONES (T3 AND T4) AS A MARKER OF UTERINE CANCER RISK FACTOR AFTER MENOPAUSE

Due to limited available information of the correla tion between T3 and T4 on uterine cancer. This stud y focused on the following: Possibility of T3 and T4 as a marker of uterine cancer by studying the relationship between T3 and T4 and uterine cancer t hrough a hormonal parameters. The study included collection of samples attending the Hospitals in Mo sul, divided to two groups (40 healthy women and 35 women diagnosed with uterine cancer only). Each pat ient was evaluated clinically and by a biochemical laboratory tests, which include estrogen, progester one, T3, T4, adiponectin and BMI in serum. The resu lts showed that T3 and T4 may increases the incidence o f uterine cancer especially after menopause because its increase significantly BMI and estrogen and decreas ed adiponectin lead to disorder in hormonal imbalan ce in women body. Novel of this research showed that t yroid hormones are a new risk factor for uterine cancer especially after menopause. Accordingly, wom en should pay attention for the level of thyroid hormones during menopausal age to reduce the risk o f uterine cancer.


INTRODUCTION
The concept that hormones can cause increase the incidence of human cancer is mainly seen in for the four hormone-related cancers which are numerically the most important, namely, breast, prostate, uterus and ovary. Even for these sites, large gaps remain in our knowledge of the responsible hormones and the conditions which create the optimal opportunity for carcinogenesis (Schottenfeld and Fraumeni, 2006). The thyroid hormones, Triiodothyronine (T3) and Thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland. Thyroid disease is commonly affecting women more than men in Iraq (Aljawadi and Altalib, 2000), thyroid dysfunction is associated with significant morbidity and mortality (Singh et al., 2008) The thyroid hormones are essential to proper development and differentiation of all cells of the human body (Fierabracci, 2011). Thyroid function may vary in obese women in association with body weight and fat mass (Reinehr, 2010), thus obesity can exacerbate the age-related decline in physical function and lead to frailty (Villareal et al., 2011). Monotonically increasing risks for excess body weight were also observed for deaths from cancer (Jiemin et al., 2011). Aim of the study is the possibility T3 and T4 as a marker of uterine cancer by studying the relationship between T3 and T4 and uterine cancer through a hormonal parameters and study the effect according to the age.

MATERIALS AND METHODS
The study included collection of samples attending the Hospitals in Mosul, from 75 women divided to two groups (40 healthy women and 35 women diagnosed with uterine cancer only). Each patient was evaluated clinically and by a biochemical laboratory tests, which include estrogen, progesterone, T 3 ,T 4 and adiponectin in serum by using commercial kits (BioMerieux Vitek, Inc., UAS), also BMI (weight (kg)/height (m) 2 ) was done.
The statistical methods used to analysis the data include mean, standard deviation, minimum and Science Publications AJAS maximum, while T-test and Anova analysis was used to compare between total control and total patients according to the occupation at p≤0.05, p≤0.01 and p≤0.001 (Kirkpatrick and Feeney, 2012). Table 1 showed a significant differs at p = 0.01, p = 0.05, p<0.001, p = 0.05 and p = 0.01 of biochemical parameters (Estrogen, Progesterone, T 3 , T 4, adiponectin and BMI) in uterine cancer women compared with control group.

DISCUSSION
Although the exact cause of uterine cancer is unknown, increased levels of estrogen appear to play a role. Estrogen helps to stimulate the buildup of the lining tissue of the uterus. Study have showed that high levels of estrogen at p = 0.01 result to excessive endometrial growth and cancer as seen in Table 1 and it was showed high correlation with thyriod hormones and utrrine cancer at 0.78. thus T3 and T4 was associated with uterine cancer at p = 0.01 and p<0.001, respectively. Thyroid disorders are common cause of abnormal bleeding thus increasing the risk of uterine cancer (Sweet et al., 2012) and lead to increase lipids, because adipose tissue is working on the production large quantities of estrogen hormone (Wright et al., 2012), thus increase BMI, The International Classification BMI according to WHO showed the normal range: 18.50-24.99 kg/m 2 , pre-obese: 25.00-29.99 kg/m 2 and obese ≥30.00 kg/m 2 (WHO, 2004), also thyroid hormones decreased production of adiponectin. Circulating levels of adiponectin, a hormone with insulin-sensitizing properties, are decreased in conditions related to obesity which are recognized risk factors for endometrial cancer, because its play an important role not only in glucose and lipid metabolism but also in the development and progression of several obesity-related malignancies (Maso et al., 2004;Kelesidis et al., 2006). as the result in Table 1 Low level of progesterone reduces the immunity of woman's body, because progesterone plays a critical role in suppressing the inflammatory signals (Singh et al., 2013). Accordingly, thyroid hormones may be serve as a novel and independent prognostic parameter for patients with uterine cancer.
Most cases of uterine cancer occur between the ages of 60 and ≤70 years, but a few cases may occur before age 40 as showed in Table 2 and this corresponding with other study which found increased uterine cancer after menopause (Park et al., 2008;Barlin et al., 2010). Because high levels of thyroid hormones lead to obesity and low levels of adiponectin, adiponectin found to be significantly associated with an increased risk for endometrial cancer postmenopausal in women (Luhn et al., 2013;Erdogan et al., 2013).
Therefore the primary prevention of cancer will probably depend on modification of the factors which affect the secretion and metabolism of the responsible hormones rather than on control of exposure to classical exogenous initiators. 0.01 *Significant differences at p = 0.05, ** Significant differences at p = 0.01, ***Significant differences at p<0.001

CONCLUSION
Novel of this research showed that high concentration of T3 and T4 especially after menopause is a risk factor for uterine cancer. Accordingly, women should pay attention for the level of thyroid hormones during menopause age and early diagnosis and treatment of thyroid disorders to reduce the risk of uterine cancer.