Risk Factors for Thyroid Cancer in Females Using a Logit Model in Lahore, Pakistan

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Introduction
Thyroid cancer is a relatively rare cancer than other but it is the most common endocrine malignancy worldwide.It is mostly found in females of almost all the geographic areas (Iftikhar et al., 2011).It is a disease in which the cancer cells are found in the tissues of thyroid gland.It is diagnosed after its symptoms appearing in patient (Thyroid Cancer Survivors Association, 2014).Thyroid cancer is more common endocrine tumor.It is mostly found in females as compared to males (Haselkorn et al., 2000;Hodgson et al., 2004;Hussain et al., 2005).According to American Cancer Society, the ratio between female and male may be high as 6:1.Approximately 2,700 new cases were found in UK each year with the female male ratio of 3:1 (Cancer Research UK, 2014).In 2014, 62,980 new cases were estimated in US and the estimated deaths RESEARCH ARTICLE Risk Factors for Thyroid Cancer in Females Using a Logit Model in Lahore, Pakistan Faiza Asif1 *, Muhammad Riaz Ahmad2 , Arshia Majid3 these cases, papillary carcinoma was found to be most common tumor (Albasri et al., 2014).Overall percentage of thyroid cancer in Pakistan is 1.2%.Similarly, the ratio of male to female patients in whole Karachi, Pakistan is 2.6 to (Shah et al., 1999).During the study in Aga Khan University Hospital, Karachi the ratio of female to male patients was 2.2 to 1 (Zuberi et al., 2004).Papillary thyroid cancer more significantly found in females and iodine excess or deficit is a big cause of papillary and follicular thyroid cancer (Verkooijen et al., 2012).The 6235 (72.5%) female cases were found among the 8603 registered cases in Florida which was three times more than males.This study was concluded that radiation exposure, occupational exposure, reproductive factors often increase the risk of thyroid cancer (Hodgson et al., 2004).The possible risk factors of the higher ratio of thyroid cancer in women may be high dose ionizing radiation, excess or shortage of iodine, hormone replacement therapy and other hormonal factors (Haselkorn et al., 2005).Smoking and use of alcohol is inversely associated with papillary and follicular carcinoma (Kitahara et al, 2012).

Materials and Methods
This case and control study of thyroid cancer was carried out in the Sheikh Zayed Hospital and INMOL Hospital, Lahore, Pakistan with the help of self-designed questionnaire.Reliability of the questionnaire was checked by Cronbach's Alpha test which was 0.74.The sample of 232 females was obtained from the selected hospitals in different visits between the months of January to May, 2013.All the requisite information was collected from the females about the characteristics like age, gender, family history of thyroid cancer, use of iodine diet, radiation therapy, etc.The dependent variable of this study was binary while the independent variables were nominal, ordinal and quantitative type.For the descriptive and analytical purpose, SPSS (Statistical Package for Social Sciences) version 16.0 was used.For the analysis, bivariate analysis and binary logistic regression model were used.All the regression coefficients, odds ratio, p-value and 95% confidence interval for odds ratio were computed.P-value is used to compare the significance of the variables with the predefined value.For the adequacy of the model, Omnibus test and Hosmer and Lemeshow (HL) test are used (Hosmer and Lemeshow, 2000).
It was observed that 97 (76.4%) patients with thyroid cancer and 75 (751.4%)patients without thyroid cancer were correctly predicted.But 38 (23.8%) cases and 39 (24.3%) controls were misclassified as 30 (23.6%) patients were not having thyroid cancer and similarly 30 (23.6%) patients were observed as having thyroid cancer, respectively.The total numbers (percentages) of correctly classified and misclassified patients were 172 (74.1%) and 60 (25.9%), respectively.As the value of correctly classified was much higher, so the fitted model was adequate.
The significant risk factors and their predictive strengths are observed in The subject having oxidative stress was observed as a highly significant factor of thyroid cancer.It had 4.115 times higher risk of thyroid cancer (OR: 4.115, 95% CI: 2.185-7.750,p=0.000).Similarly intake of fast food more than 2 days in a week was 3.656 time higher positively significant with thyroid cancer (OR: 3.656, 95% CI: 1.851-7.223,p=0.000).Same as the subject used fried food more than 2 days in a week had 2.360 times higher risk of thyroid cancer (OR: 2.360, 95% CI: 1.199-4.643,p=0.013).Family history of cancer was significantly associated with thyroid cancer (OR: 2.630, 95% CI: 1.416-4.887,p=0.002).Marital status was also positively significant with thyroid cancer (OR: 2.152, 95% CI: 1. 104-4.198, p=0.024).

Discussion
Thyroid cancer is found to be one of the most common and rapidly increased cancer in the world.It is mostly found in women than men.According to the study of Albasri, thyroid cancer has become the second most common tumor in the Saudi women.The male to female ratio in this region is 4:29 (Albasri et al., 2014).The ratio of thyroid cancer in male to female is 1:4 in Pakistan and in Karachi this ratio is 2.2:1.It is mostly observed between the age group of 30 to 60 years (Zuberi et al., 2004).The incidence of thyroid cancer was found high among the females of Baluchistan than males.Among 87 cases, 58 were females and among these 58 females, 53% cases belonged to 21-40 years age group (Iftikhar et al., 2011).
The main objective of this study is to identify the significant risk factors which cause of thyroid cancer.According to present study, oxidative stress is found to be the highest risk factor of the thyroid cancer as compared to the other risk factor.The odd ratio and 95% CI indicates that the oxidative stress had 4.115 times higher risk of thyroid cancer as compared to the other.Another study showed that the increased levels of oxidants and decreased As, it represent the instability between the production of oxidants and removal of the anti-oxidative molecule in the body (Xing, 2012).The oxidation level disturbance in the blood of the thyroid cancer patients is due to the superoxide anion (free radical which produce during psychological cellular metabolism and inflammation).
The excess of superoxide anion damage the DNA badly and also it showed the clearly involvement of oxidative stress in thyroid cancer (Metere et al., 2012).
According to this study, consumption of low and high iodine diet has 2.391 times higher risk of thyroid cancer, as it is directly related to thyroid cancer.Maso (2013) investigated low level Iodine is, in fact, strongly associated with thyroid cancer incidence, via benign thyroid conditions such as goiter and nodules, which are the cause of thyroid cancer.Excess and deficiency of iodine become the cause of autoimmune thyroid disorder like goiter and nodules (Prummel et al., 2004).Papillary carcinoma is mostly found in high iodide intake areas and low in areas with low dietary iodide (Williams et al., 1997).Like the other countries, iodine deficiency is the well recognized problem in Pakistan.Due to lack knowledge of consumption and intake of iodine nutrition thyroid hormones are affected.It also becomes the cause of pregnancy loss (Elahi et al., 2003).Different types of thyroid carcinoma are related to low and high iodine diet.Low iodine diet becomes the cause of follicular and anaplastic cancer and high iodine diet becomes the cause of papillary thyroid carcinoma.The incidence of thyroid cancer is similar to in iodine deficiency regions (Rasmussen, 2001).Thyroid cancer is directly significant to family history of thyroid cancer and intake of low iodine diet (Xhaard et al., 2014).Iodine is necessary for the production of thyroxine.Low level of iodine reduces the production of hormones.In such situation thyroid work harder to produce hormone which become the cause of enlargement and as well as goiter.In pregnancy iodine deficiency increased the risk of miscarriage (Park et al., 2005).
This study indicate the use of fast food items is positively significantly associated with thyroid cancer and the subject who are using fast food items more than 2 days per week have 3.656 times high risk of thyroid cancer.The use of butter and cheese in diet is positively associated with increasing the risk of thyroid cancer having OR=1.6,CI, 1.1-2.5 and OR=1.5, 1.0-2.4(Galanti et al, 1997).The use of whole wheat and rye also contain iodine and the quantity of iodine among in these things depend on soil where these grown.Moreover the sea fish, shellfish, salad and pasta dishes have sufficient iodine intake (Vegetarian and Vegan Foundation, 2013).This study shows that consumption of fried food more than 2 days per week has 2.360 times higher risk of thyroid cancer with the CI (1.199, 4.643).The role of diet is positively associated with the thyroid cancer.Mostly nutritional factors are related with the risk of thyroid cancer (Galanti et al., 1997).
It is also seen from that study, thyroid cancer is common among those whose has family history of cancer with 2.630 odds ratio (1.416-4.887),which indicated that the a person having family history of disease having 2.630 times risk of getting disease.According to the study of Martin et al, 1993 the most of the cases whose reported has a first degree relative suffered from thyroid disease.The genetic transformation is also responsible for the thyroid cancer incidence (Perrier et al., 1998).Genetics factors are 20-25% responsible for all the type of thyroid cancer.There is also a strong association among thyroid cancer and history of benign nodules and goiter (Maso et al., 2009).
In conclusion, thyroid cancer becomes a common cancer in Pakistan.It is mostly found among the female patients of age group (15-60).The ratio of papillary carcinoma is very high among all the types.It is concluded that oxidative stress, use of high and low iodine diet, genetic cancer history, excess of fast and fried food increase the risk of thyroid cancer.

Table 2 . Variables in the Equation
Wang et al., 2011).High oxidative stress is a new and strongly associated risk factor of thyroid cancer.