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Kwq513 1183.119

American Journal of Epidemiology ª The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of DOI: 10.1093/aje/kwq513 Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Advance Access publication: Original Contribution Long-Term Sedentary Work and the Risk of Subsite-specific Colorectal Cancer Terry Boyle*, Lin Fritschi, Jane Heyworth, and Fiona Bull * Correspondence to Terry Boyle, Western Australian Institute for Medical Research, University of Western Australia, B Block, QueenElizabeth II Medical Centre, Hospital Avenue, Nedlands, Western Australia 6009, Australia (e-mail: tboyle@waimr.uwa.edu.au).
Initially submitted September 27, 2010; accepted for publication December 22, 2010.
Research suggests that sedentary behavior may increase the risk of some chronic diseases. The aims of the study were to examine whether sedentary work is associated with colorectal cancer and to determine whetherthe association differs by subsite. A total of 918 cases and 1,021 controls participated in a population-basedcase-control study of colorectal cancer in Western Australia in 2005–2007. Data were collected on lifestyle,physical activity, and lifetime job history. The estimated effects of sedentary work on the risk of cancers of the proximal colon, distal colon, and rectum were analyzed by using multinomial logistic regression. Compared withparticipants who did not spend any time in sedentary work, participants who spent 10 or more years in sedentarywork had almost twice the risk of distal colon cancer (adjusted odds ratio ¼ 1.94, 95% confidence interval: 1.28,2.93) and a 44% increased risk of rectal cancer (adjusted odds ratio ¼ 1.44, 95% confidence interval: 0.96, 2.18).
This association was independent of recreational physical activity and was seen even among the most recrea-tionally active participants. Sedentary work was not associated with the risk of proximal colon cancer. These resultssuggest that long-term sedentary work may increase the risk of distal colon cancer and rectal cancer.
colorectal neoplasms; motor activity; occupations; sedentary lifestyle Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; MET, metabolic equivalent.
Research suggests that sedentary behavior may increase activity modified the effect of sedentary work on colorectal the risk of some chronic diseases (1). Sedentary behavior cancer risk. Additionally, few of these studies have inves- is characterized by prolonged sitting and other activities tigated the effect of long-term sedentary work on the risk of requiring very low energy expenditure (<1.5 metabolic colorectal cancer; most have examined only occupational equivalents (METs)) (1–3) and is considered to be an inde- activity at 1 point in time.
pendent exposure, distinct from low levels of physical Another unresolved issue is whether sedentary work has a activity (1). Research on the more well-recognized risk different effect on distal and proximal colon cancer risks. It factor of physical activity has shown that a low level of has been suggested that distal and proximal colon cancers work-related activity is associated with an increased risk may in fact be 2 different diseases: There are morphological, of colorectal cancer (4). However, these studies have mostly molecular, and epidemiologic differences between distal compared light-intensity occupations (or combined seden- and proximal colon cancers, and research suggests that they tary and light-intensity occupations) with physically active may have different environmental and genetic risk factors work. Physical activity and sedentary behavior (often called (5). Different effects by tumor subsite may have screening ‘‘too much sitting'') may act through different mechanisms implications (6) and may provide further clues into the eti- (1) and, as such, it is not clear if a low level of physical ology of colon cancer.
activity, a high level of sedentary behavior, or a combination We conducted a case-control study to investigate these of both is behind the associations seen. Previous studies issues. The aims of the study were as follows: to examine have generally not adjusted for recreational physical activity whether sedentary work was associated with colorectal and also have not investigated whether recreational physical cancer; to determine whether the association differed by Am J Epidemiol. 2011;173(10):1183–1191 Boyle et al.
Selected Characteristics of the Participants, by Outcome, the Western Australian Bowel Health Study, 2005–2007 Socioeconomic status 1 (most disadvantaged) 5 (least disadvantaged) Smoking, pack-years Body mass index at age 20 years, kg/m2a Body mass index at age 40 years, kg/m2a subsite; and to investigate whether recreational physical lanoma skin cancer, it is mandatory to register all cases of activity modified the effect of sedentary work on colorectal cancer in Australia. Carcinomas occurring in the hepatic cancer risk.
flexure, cecum, ascending colon, and transverse colon wereclassified as proximal colon cancers; carcinomas occurringin the splenic flexure, descending colon, and sigmoid colon MATERIALS AND METHODS were classified as distal colon cancers; and carcinomas oc-curring in the rectosigmoid junction and rectum were clas- The Western Australian Bowel Health Study sified as rectal cancers. Controls were randomly selected A case-control study called the Western Australian Bowel from the Western Australian electoral roll, which is consid- Health Study (WABOHS) took place in Western Australia ered to be virtually complete as registration on the electoral between 2005 and 2007. Details of this study have been roll is compulsory in Australia. Information on lifestyle, described previously (7). Briefly, all participants were aged diet, occupation, and medication use was collected by using between 40 and 79 years and resided in Western Australia.
self-administered questionnaires from 918 histopathologi- Incident cases of colorectal cancer occurring between June cally confirmed cases (59.5% response fraction) and 1,021 2005 and August 2007 were recruited through the Western age- and sex-matched controls (46.5% response fraction).
Australian Cancer Registry. With the exception of nonme- Forty-eight cases and 25 controls were excluded because of Am J Epidemiol. 2011;173(10):1183–1191 Sedentary Work and Colorectal Cancer Risk Diabetes and/or high Energy intake from food 10 years ago, kJ/day Alcohol consumption 10 years ago, g/day Total lifetime recreational physical activity lifetime recreationalphysical activity a Total case and control numbers do not add up because of missing data.
missing data on 1 or more covariates, leaving 996 controls professionals); 2) light (e.g., teachers, hairdressers, house- and 870 cases in this analysis. Ethics approval for the Western wives); 3) medium (e.g., mechanics, police officers, nurses); Australian Bowel Health Study was obtained from the Uni- 4) heavy (e.g., plumbers, farmers); and 5) very heavy (e.g., versity of Western Australia Human Research Ethics Commit- miners, fire fighters). The heavy and very heavy catego- tee and the Confidentiality of Health Information Committee ries were combined as there were few participants in the within the Western Australian Department of Health, and writ- very heavy category. Jobs classified as sedentary by the Dic- ten informed consent was obtained from all participants.
tionary of Occupational Titles involve sitting most ofthe time, while light jobs involve activity of a light intensity Exposure measurement The number of years that a participant spent in each level Participants were asked to complete their lifetime occu- of occupational activity was calculated. Part time, casual, pational history, from their first job to retirement. For each and seasonal occupations were considered to be equivalent job that a participant held, he/she was required to record the to 0.5, 0.25, and 0.25 years of full-time work, respectively. A job title and duties, company, location, age started and stop- lifetime occupational activity variable was created by as- ped, and whether the job was full time, part time, casual, or signing participants to the occupational activity category seasonal. Occupational physical activity was calculated by in which they spent the most time. As more than half of classifying each job (based on job title and duties) that a the participants were in the ‘‘light'' category, this was used participant held into one of 5 categories of Physical as the reference level in the model that assessed the effect Demands Strength Rating, according to the US Department of lifetime occupational activity on colorectal cancer. To of Labor's Dictionary of Occupational Titles (8). The 5 further quantify the effect of sedentary work on colorectal categories are 1) sedentary (e.g., bookkeepers, computing cancer, we categorized the number of years spent in Am J Epidemiol. 2011;173(10):1183–1191 Boyle et al.
sedentary work as none, more than zero but less than 10 included an interaction term in the full model. Recreational years, and 10 or more years. The latter 2 categories were physical activity was considered to be a potential effect modi- determined from the distribution among controls that led to fier and is an established risk factor for colorectal cancer. We 2 groups of roughly equal size.
also examined whether vigorous recreational physical activityor body mass index at age 40 years modified the effect of Statistical analysis sedentary work on colorectal cancer risk. Postestimation com-mands were used to generate odds ratios and confidence in- Polytomous logistic regression models were used to esti- tervals for the models that included an interaction term.
mate the odds ratio for the risk of proximal colon cancer, Chi-square tests were used to assess the differences be- distal colon cancer, and rectal cancer. Postestimation com- tween outcomes for the selected characteristics in Table 1.
mands were used to test whether the effect of each exposure All P values were 2 sided.
differed significantly by subsite (9). As this was an imputed The controls were selected from the electoral roll, but we data set (see below), the command ‘‘MIM'' was used to did not exclude the cases who were not on the electoral roll.
generate parameter estimates (10). All analyses were per- We therefore conducted a sensitivity analysis, in which we formed by using STATA, version 11.1, statistical software repeated all analyses without cases who were not on the (StataCorp LP, College Station, Texas).
electoral roll (n ¼ 54) and compared the effect sizes with Sex and age group (5 year) were included in all models, those from the original models.
as the control distribution was matched to the case distribu- There was no statistically significant interaction by sex in tion on these variables. Energy intake 10 years ago, cigarette any of the analyses, and the associations observed were use, alcohol intake 10 years ago, diabetes, socioeconomic similar in both sexes, so all results are presented for males status, body mass index at ages 20 and 40 years, and lifetime and females combined.
recreational physical activity were included in the final anal-yses as they are established risk factors for colorectal cancer and were considered to be potential confounders (11).
The model assessing the effect of years in sedentary work The demographic and various dietary and lifestyle char- additionally adjusted for combined years in heavy and very acteristics of the participants by cancer status are shown in heavy occupational activity. Energy intake (kJ/day from Table 1. There was a higher proportion of females among food) and alcohol intake (g/day) were categorized on the the proximal colon cancer cases than the distal colon or basis of the control quartiles. Cigarette use was categorized rectal cancers. The age distribution among participants with into 3 groups (0, 1–19, 20 pack-years). Diabetes was proximal colon cancer was significantly different from that classified as having diabetes, high blood sugar level only, of participants with distal colon cancer or rectal cancer, with or neither. Socioeconomic status was classified by using 79% of proximal colon cancer aged over 60 years compared the Index of Relative Socio-economic Disadvantage from with 65% of distal colon cancer cases and 68% of rectal the Socio-Economic Indexes for Areas (12) and was cate- cancer cases. Participants from more disadvantaged areas gorized into 5 groups. Body mass index was classified as were more likely to have rectal cancer than distal colon under or normal weight (<25 kg/m2), overweight (25–29.9 cancer. Compared with all cases, controls were less likely kg/m2), and obese (30 kg/m2). Body mass index at ages to be 20 pack-year smokers and were also less likely to 20 years and 40 years was imputed by using the multiple have diabetes. Proximal colon cancer cases were less likely imputation command ‘‘ICE'' (13), as there were 8% missing than distal colon or rectal cancer cases to be overweight or data for these variables.
obese at 20 years of age.
Information on recreational physical activity performed Compared with participants who spent the most time in a over the adult lifetime was collected by using a question- light job, participants who spent the most time in a sedentary naire based upon others that have been shown to be reliable occupation had 2 times the risk of distal colon cancer (ad- (14–16). Participants were asked to record the recreational justed odds ratio (AOR) ¼ 2.07, 95% confidence interval physical activity that they performed regularly (>10 times) (CI): 1.25, 3.44) (Table 2). Participants who spent 10 or during 3 periods of their life (up to the date of their partic- more years in sedentary work had almost twice the risk of ipation in the study): 19–34 years; 35–50 years; and 51 years distal colon cancer (AOR ¼ 1.94, 95% CI: 1.28, 2.93) and or more. For each age period, a MET-hours per week total nearly 1.5 times the risk of rectal cancer (AOR ¼ 1.44, 95% was calculated. This total was then categorized as no phys- CI: 0.96, 2.18) compared with participants who never held a ical activity (i.e., 0 MET-hours per week), and the remaining sedentary occupation (Table 2). When the interaction term active participants were split into 3 groups of roughly equal between total recreational physical activity and sedentary size (0.1–11.9, 12–29.9, and 30 MET-hours per week). A work was included in the model (Table 3), it was not statisti- lifetime recreational physical activity score was created by cally significant (P ¼ 0.29). The risk of distal colon cancer summing the category (0, 1, 2, or 3) from each age period.
and rectal cancer increased with increasing duration of sed- The total score was then split into 2 groups (0–4, 5–9 for entary work among both the most recreationally active and participants aged 51 years or older; 0–2, 3–6 for participants least recreationally active participants (Table 3). The risk of aged <51 years). This was also done for vigorous activities proximal colon cancer was not linked with sedentary work (activities with a MET value of 6 or more) only.
in the whole population (Table 2), the most recreationally To determine whether recreational physical activity modi- active participants, or the least recreationally active partic- fied the effect of sedentary work on colorectal cancer risk, we ipants (Table 3). Neither vigorous recreational physical Am J Epidemiol. 2011;173(10):1183–1191 Association Among Lifetime Occupational Activity, Years in Sedentary Work, and Site-specific Colorectal Cancer Risk, the Western Australian Bowel Health Study, 2005–2007 occupational activity Years in sedentary work Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; OR, odds ratio.
a Adjusted for age group and sex.
b Adjusted for age group, sex, lifetime recreational physical activity level, cigarette smoking (pack-year tertiles), diabetes, educational level, energy intake from food, alcohol intake, body mass index at age 20 years, body mass index at age 40 years, and socioeconomic status. The AOR in the ‘‘years in sedentary work'' analysis is additionally adjusted for years in a heavy or veryheavy occupation.
c P < 0.05 for the difference between the proximal colon and the distal colon.
d P < 0.05 for the difference between the proximal colon trend and the distal colon trend.
by guest on August 8, 2016 Boyle et al.
Effects of Lifetime Recreational Physical Activity and Body Mass Index on the Association Between Years in Sedentary Work and Site- specific Colorectal Cancer Risk, the Western Australian Bowel Health Study, 2005–2007 Proximal Colon Cancer by Distal Colon Cancer by Lifetime Recreational Lifetime Recreational Lifetime Recreational Physical Activity Physical Activity Physical Activity Abbreviations: AOR, adjusted odds ratio; CI, confidence interval.
a Adjusted for age group, sex, lifetime recreational physical activity level, cigarette smoking (pack-year tertiles), diabetes, educational level, energy intake from food, alcohol intake, body mass index at age 20 years, body mass index at age 40 years, socioeconomic status, and years in aheavy or very heavy occupation.
activity nor body mass index at age 40 years modified the occupation in the past year involved mainly sitting had a association between years in sedentary work and colorectal 67% greater risk of colon cancer and a 41% increased risk of cancer (data not shown).
rectal cancer than those who reported ‘‘walking quite a lot'' Participants who spent the most time in jobs requiring in their occupation, although neither of these associations heavy or very heavy activity had a significantly reduced risk reached statistical significance, and the authors did not find of proximal colon cancer (AOR ¼ 0.56, 95% CI: 0.32, 0.96) an association between sedentary behavior in leisure time compared with participants who spent the most time in a and colon or rectal cancer risk. Finally, Steindorf et al. (28) light job (Table 2).
found that those who spent more than 2 hours a day watch- There were no meaningful changes to the effect estimates ing television more than doubled their risk of colorectal in the above analyses when the cases that were not on the cancer compared with those who spent less than 1.14 hours electoral roll were excluded.
a day watching television.
The positive association found between sedentary work and colorectal cancer in this study was independent of rec-reational physical activity and was seen among the most In this study, we found that participants who spent the recreationally active participants. Indeed, even a high level most time in sedentary work had a risk of distal colon cancer of vigorous recreational physical activity did not modify the that was 2 times higher than those who spent the most time effect of sedentary work. This finding fits with the ‘‘Active in a job requiring light activity. Similarly, participants who Couch Potato'' phenomenon, in which high amounts of sed- spent 10 or more years in sedentary work had almost twice entary behavior and physical activity coexist, and lends sup- the risk of distal colon cancer and almost 1.5 times the port to the notion that sedentary behavior affects disease risk risk of rectal cancer, of those who did not do any sedentary independently of physical activity (1).
work. Proximal colon cancer risk was not associated with There are several plausible biologic mechanisms through sedentary work, although the risk was significantly reduced which sedentary work and sedentary behavior in general among participants who spent the most time in jobs requir- may increase the risk of colorectal cancer (refer to reference ing heavy or very heavy activity.
30 for a review of the evidence and proposed mechanisms Previous research that has investigated the association linking sedentary behavior and cancer). Sedentary behavior between long-term exposure to a low level of work-related has been shown to increase blood glucose levels and to activity and colorectal cancer has generally found an decrease insulin sensitivity, independently of physical activ- increased risk (17–25), although these studies have in the ity (31). Increased blood glucose and decreased insulin re- main compared light-intensity work with more physically sistance are both thought to promote colorectal cancer active work. The 4 studies that have investigated the effect carcinogenesis (32, 33). Sedentary behavior has also been of time spent sitting, or a proxy measure, on colorectal linked to an increased risk of diabetes and obesity (again cancer risk have all revealed an increased risk (26–29).
independently of exercise level) (34), both of which are Howard et al. (27) found that participants who spent 9 or established risk factors for colorectal cancer (11). Bed-rest more hours per day sitting had a 25% greater risk of colon studies and experiments on mice provide some evidence that cancer than those who spent less than 3 hours per day sitting.
sedentary behavior is associated with markers of inflamma- Whittemore et al. (29) found that, compared with Chinese- tion and mitochondrial function (30). Other proposed mech- American men who spent less than 5 hours sitting, those anisms through which sedentary behavior may increase the who spent 5–9 hours sitting had 2.4 times the risk of colo- risk of colorectal cancer include increasing levels of proin- rectal cancer, and participants who spent 10 or more hours flammatory factors, decreasing levels of antiinflammatory sitting had 3.9 times the risk of colorectal cancer. Colbert factors, and decreasing levels of vitamin D (30). Although et al. (26) found that participants who reported that their several of these mechanisms are the same as those proposed Am J Epidemiol. 2011;173(10):1183–1191 Sedentary Work and Colorectal Cancer Risk for the inverse relation between physical activity and color- uals who are physically active in their leisure time. Some ectal cancer (35), many of them appear to act independently countries, including Australia (54), Canada (55), and the of physical activity. It has also been proposed that the loss of United Kingdom, have or are developing sedentary behavior local contractile activity caused by sitting results in unique recommendations for early years (<5 years of age), chil- gene expressions that may be involved in disease etiology dren, and/or adults.
(36). Sitting has been shown to suppress the regulation of This study had several limitations. Selection bias is a skeletal muscle lipoprotein lipase, which plays an important possible explanation for the results, especially given the role in lipid metabolism and may have a positive effect on low response fraction among the controls (46.5%). Basing diet-induced adiposity and insulin resistance (36).
occupational activity level on job title is not an ideal assess- Our finding that sedentary work is associated with the risk ment and may have led to nondifferential exposure misclas- of distal colon cancer but not proximal colon cancer adds to sification. Recreational activity was determined by self- the evidence suggesting that lifestyle factors may play a report of activities; however, this approach to measuring larger role in distal colon carcinogenesis than in proximal physical activity has been found to be reliable and valid colon carcinogenesis (37). Fruit and vegetable intake (38), (56). We had data on only sedentary behavior in 1 domain calcium intake (39), and meat consumption (40) all appear to (occupation) and were not able to take into account seden- be more strongly associated with distal colon cancer than tary behavior during leisure time, at home, or during trans- proximal colon cancer, although the literature concerning port. This study also had several strengths. It was a physical activity and distal and proximal colon cancer is population-based study with histopathologically confirmed inconsistent (41). There is no clear mechanistic explanation, cases, and we were able to control for many potential con- however, for why sedentary behavior would increase the risk founders including lifetime recreational physical activity.
of distal colon and rectal cancers but not proximal colon We were also able to investigate whether recreational phys- cancer. Obesity is one possibility: An increased body mass ical activity modified the effect of sedentary work on color- index may have a greater effect on distal colon cancer (37), ectal cancer risk.
and there is evidence that obesity has a greater effect on Aside from the increased risk of distal colon cancer microsatellite-stable tumors (42), which are more likely to and rectal cancer seen among those who worked in a occur in the distal colon than the proximal colon (5). There is sedentary occupation for 10 or more years in this study, some evidence that vitamin D has a stronger protective effect an increasing level of sedentary behavior has been linked on distal colon and rectal cancers than proximal colon cancer to an increased risk of several other chronic diseases, as (43); however, there is little evidence that insulin affects well as increased mortality (57, 58). Sedentary behavior proximal and distal colon cancers differently (44–47), and appears to be a novel and important risk factor for many antiinflammatories may have a more pronounced protective chronic diseases (59).
effect on proximal tumors than distal tumors (48, 49). Fur-ther mechanistic evidence is needed to understand why the association between sedentary behavior (and lifestyle factorsin general) and colon cancer may differ by subsite.
The findings of this study have occupational health im- Author affiliations: School of Population Health, the Uni- plications, especially given that advances in technology versity of Western Australia, Perth, Australia (Terry Boyle, have led to increasing amounts of sedentary behavior at Jane Heyworth, Fiona Bull); and Western Australian Insti- work and in other settings. Findings from the National tute for Medical Research, the University of Western Health and Nutrition Examination Survey suggest that the Australia, Perth, Australia (Terry Boyle, Lin Fritschi).
average American adult spends 55% (7.7 hours) of his/her This work was supported by the Australian National waking time sedentary (50). This percentage increases to Health and Medical Research Council (grant 353568).
more than 60% (8 hours) among adults aged 60 years or T. B. is supported by an Australian Postgraduate Award from more. Sedentary work is unlikely to be eliminated from the University of Western Australia and a scholarship from modern life. However, strategies to minimize the amount the Lions Cancer Institute of Western Australia. L. F. is of time spent sitting, especially long bouts of sitting, have supported by an Australian National Health and Medical been suggested (1). For example, it has been suggested that Research Council fellowship.
new occupational regulations could be introduced to break The authors thank Barry Iacopetta, Cameron Platell, up prolonged sedentary time by taking regular nonsitting Kieran McCaul, David Crawford, Cassandra Clayforth, Jenny ‘‘breaks'' (1), which have been shown to have a beneficial Landrigan, Jen Girschik, Clare Tran, Beatriz Cuesta-Briand, effect on metabolic biomarkers (51). A recent systematic and Anna Timperio for their contributions to this study.
review, however, found that there is a lack of evidence con- Conflict of interest: none declared.
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Progesterone level and progesterone/estradiol ratio on the day of hcg administration: detrimental cutoff levels and new treatment strategy

Progesterone level and progesterone/estradiol ratio onthe day of hCG administration: detrimental cutofflevels and new treatment strategy Eman A. Elgindy, M.D. Department of Obstetrics and Gynecology, Zagazig University School of Medicine; and Al-Banoon Fertility Center, Zagazig,Egypt Objective: To identify if there are certain cutoff levels for P and or the P/E2 ratio on the day of hCG that would bedefined as detrimental for occurrence of pregnancy in women with normal ovarian reserve undergoing cleavage-stage embryo transfer (ET). Secondarily, to determine if these same cutoffs might have the same potentialnegative effect in women undergoing blastocyst ET.Design: Prospective cohort study including two randomized cohorts.Setting: Private and university fertility centers.Participant(s): A total of 240 women undergoing long agonist protocol with at least four grade 1 day 3 embryos.Intervention(s): Women were randomized in a 1:1 ratio to undergo day 3 or day 5 embryo transfer.Main Outcome Measure(s): Clinical pregnancy rate (CPR) was the primary outcome.Result(s): Using receiver operator characteristics, cutoffs for P and P/E2 ratio were 1.5 ng/mL and 0.55, respec-tively. Patients with P %1.5 ng/mL and P/E %