Induced and spontaneous abortion and breast cancer risk: results from the E3N cohort study

Recent reviews reach conflicting conclusions on breast cancer risk after spontaneous or induced abortion. E3N is a large-scale cohort study collecting detailed information on environmental and reproductive factors. We investigated the relation between breast cancer and a history of induced and/or spontaneous abortion, using the data from the 100,000 women aged 40-65 at entrance in 1990. Among them, over 2,600 new invasive breast cancers had been diagnosed by June 2000. Multivariate analysis, adjusted for known potential confounders, showed no association between a history of induced abortion and breast cancer risk either in the whole population (relative risk [RR] = 0.91, 95% confidence interval [CI] 0.82-0.99) or in subgroups defined by parity or by menopausal status. Overall, the association between spontaneous abortion and breast cancer was not significant (RR = 1.05, 95% CI 0.95-1.15). However, there is a suggestion of increased risk with increased number of miscarriages (RR = 1.20, 95% CI 0.92-1.56 after 3 or more). Moreover, an interaction with menopausal status was observed. In premenopause, the risk decreased with increasing number of spontaneous abortions, whereas it increased in postmenopause. Among nulliparous and parous women, the relative risk estimates were respectively equal to 1.16 (95% CI 1.04-1.30, p trend < 0.0008) and 1.14 (95% CI 1.01-1.28, p trend = 0.005). Premenopausal breast cancer, on the other hand, appeared to be less frequent in women who had had repeated miscarriages. We conclude that there is no relationship between breast cancer and induced abortion but that an association with spontaneous abortion is possible and may depend on menopausal status.     

Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women

Objective: To examine the relationship between breast cancer risk and the cumulative number of cycles before a first full-term pregnancy (FTP) and lifetime, taking age at menarche and at onset of regular cycling, periodicity and regularity of cycles, duration of periods of pregnancy, and lactation, oral contraceptive (OC) use, and age at menopause into account. Methods: The data were taken from the E3N prospective cohort study of women aged 40–65 years in 1990. A total of 1718 breast cancer cases were identified during the 579,525 person-years of follow-up. Results: There was a highly significant linear relationship between breast cancer risk and both the cumulative number of cycles before a first FTP (p for trend < 0.0001) and lifetime (p for trend < 0.001), with multivariate relative risk (RR) of a similar magnitude for both variables. Compared to women with a lifetime number of cycles 402 ( 30 years), the RR for those with a lifetime total of 403–441, 442–480, 481–520, and 521 cycles were 0.95 (0.75–1.21), 1.21 (0.97–1.52), 1.23 (0.96–1.58), and 1.60 (1.25–2.04), respectively. Results restricted to never OC users were similar. Conclusions: Further investigation is needed to clarify whether the underlying factor is repeated exposure to fluctuating hormones, the number of anovular/ovular cycles, or the relative importance of the follicular and luteal phases.     

Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study.

PURPOSE: There is a need to investigate the type, duration, frequency, and intensity of physical activity that are critical to reduce the risk of breast cancer, and if this relation differs among subgroups of women.METHODS: We analyzed the relation between physical activity and breast cancer incidence between 1990 and 2002 (n=3,424 cases), among 90,509 women of the French E3N cohort, ages between 40 and 65 years in 1990. We gave special attention to effect modification by body mass index (BMI), family history of breast cancer, parity, and hormone replacement therapy (HRT).RESULTS: A linear decrease in risk of breast cancer was observed with increasing amounts of moderate (P(trend)<0.01) and vigorous (P(trend)<0.0001) recreational activities. Compared with women who reported no recreational activities, those with more than five weekly hours of vigorous recreational activity had a relative risk of 0.62 (0.49-0.78). This decrease was still observed among women who were overweight, nulliparous, had a family history of breast cancer, or used HRT. Compared with the whole cohort, among nulliparous women, the reduction of risk observed was of a higher magnitude, although the test for heterogeneity did not reach statistical significance.CONCLUSION: A risk reduction of breast cancer was particularly observed with vigorous recreational activity. Further investigations are needed to confirm that intensity is an important variable to consider in risk reduction and to identify the precise biological mechanisms involved in such a risk reduction.     

Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study

Large numbers of hormone replacement therapies (HRTs) are available for the treatment of menopausal symptoms. It is still unclear whether some are more deleterious than others regarding breast cancer risk. The goal of this study was to assess and compare the association between different HRTs and breast cancer risk, using data from the French E3N cohort study. Invasive breast cancer cases were identified through biennial self-administered questionnaires completed from 1990 to 2002. During follow-up (mean duration 8.1 postmenopausal years), 2,354 cases of invasive breast cancer occurred among 80,377 postmenopausal women. Compared with HRT never-use, use of estrogen alone was associated with a significant 1.29-fold increased risk (95% confidence interval 1.02–1.65). The association of estrogen–progestagen combinations with breast cancer risk varied significantly according to the type of progestagen: the relative risk was 1.00 (0.83–1.22) for estrogen–progesterone, 1.16 (0.94–1.43) for estrogen–dydrogesterone, and 1.69 (1.50–1.91) for estrogen combined with other progestagens. This latter category involves progestins with different physiologic activities (androgenic, nonandrogenic, antiandrogenic), but their associations with breast cancer risk did not differ significantly from one another. This study found no evidence of an association with risk according to the route of estrogen administration (oral or transdermal/percutaneous). These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone.     

C-reactive protein levels and subsequent cancer outcomes: results from a prospective cohort study

Chronic inflammation has been implicated in the pathogenesis of many common chronic diseases, including cancer. C-reactive protein (CRP) concentration is a non-specific serum marker of inflammation, and higher levels have been observed among individuals who go on to develop cardiovascular disease. Nested case-control studies were conducted within the CLUE II study, a community-based cohort, to examine the association between CRP concentrations and subsequent development of colorectal or prostate cancer. CRP concentrations were higher among individuals who went on to develop colon cancer, but not rectal or prostate cancer, compared with controls. The association between CRP concentrations and development of colon cancer is consistent with other evidence suggesting a role of inflammation and cancer. Preventive interventions that decrease systemic chronic inflammation have the potential to reduce certain types of cancer as well as cardiovascular disease. However, the potential benefits of anti-inflammatory chemopreventive agents must be weighed against their adverse effects before widespread use is recommended.     

Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study

We analysed the relation between adult breast cancer risk and adiposity in ages 8-25, and among 90 509 women included in the E3N cohort study, and investigated the potential modification effect of certain factors. Participants completed a questionnaire that included a set of eight silhouettes corresponding to body shape at different ages. During the follow-up (mean=11.4 years), 3491 breast cancer cases were identified. Negative trends in risk of breast cancer with increasing body silhouettes at age 8 and at menarche were observed, irrespective of menopausal status, with relative risks of 0.73 (0.53-0.99) and 0.82 (0.66-1.02) for women who reported a silhouette equal or greater than the fifth silhouette at age 8 and at menarche, respectively. We observed no clear effect modification by age at menarche, delay between age at menarche, regular cycling, regularity of cycles in adult life or body mass index at baseline.     

Fat consumption and breast cancer: preliminary results from the E3N-Epic cohort]

Recent reviews have concluded that a high consumption of total, saturated or animal, fat could possibly increase the risk of breast cancer. However these results are highly dependent on the type of study; indeed, most of the prospective studies do not support this association. In this paper, we investigated the relationship between fat consumption and breast cancer risk in the E3N-Epic cohort, the French component of the European Prospective Investigation into Cancer and Nutrition. Assessment of fat consumption was based on daily intakes of food items and nutrients using a food-frequency questionnaire. Relative risk (RR) estimates were calculated using Cox's proportional hazards model. After an average of 3.4 years of follow-up, 838 cases of incident breast cancer were recorded in a study population of 65,879 women. The mean caloric intake was 2,073 kcal (SD 540), with 37% of calories coming from fat intake. Milk products and vegetable oils were the main sources of fat in the diet. We found a small positive association between fat intake and breast cancer risk. Compared with the lowest, women in the highest quartile of fat intake had a 37% higher risk of breast cancer (RR 1.37, CI95% = 0.99-1.89). There was no detectable association between fatty acids or food items contributing to fat intake and breast cancer risk. These analyses suggest there is a need for longer follow-up time to increase statistical power and confirm these tendencies.     

Prediagnostic body size and breast cancer survival in the E3N cohort study

Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist‐to‐hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer‐specific, and disease‐free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)_{>100vs < 95 cm} = 1.38, 95% Confidence Interval (CI) = 1.02–1.86, P_trend = 0.02) and from breast cancer (HR_{>100vs < 95 cm} = 1.50, CI = 1.03–2.17, P_trend = 0.03), and of second invasive cancer event (HR_{>100vs < 95 cm} = 1.36, CI = 1.11–1.67, P_trend = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference.     

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925–1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05–4.69]; 4th quartile: OR = 2.33 [CI = 1.11–4.90]); P_trend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07–5.65]; 4th quartile: OR = 2.76 [CI = 1.21–6.30]; P_trend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER−: OR = 15.40 [CI = 1.84–129.19]; PR−: OR = 3.47 [CI = 1.29–9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER−: OR = 7.73 [CI = 1.46–41.08]; PR−: OR = 3.44 [CI = 1.30–9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.     

C-reactive protein and risk of breast cancer

Chronic inflammation is hypothesized to be associated with breast cancer development. However, data evaluating the association between C-reactive protein (CRP), a marker of systemic inflammation, and breast cancer risk are sparse. In the Women's Health Study, 27,919 apparently healthy women aged 45 years and older who were free of cancer and cardiovascular disease had plasma CRP levels measured at baseline. During a mean of 10 years of follow-up, a total of 892 women developed invasive breast cancer. All statistical tests were two-sided. Baseline plasma CRP level was not statistically significantly associated with breast cancer risk (highest versus lowest quintile of CRP, multivariable hazard ratio = 0.90, 95% confidence interval = 0.71 to 1.16; P(trend) = .19; crude incidence rates: 273 versus 305 per 100,000 person-years). Our data suggest that baseline plasma CRP levels are not associated with the increased risk of breast cancer in apparently healthy women.     

Mediterranean diet adherence and risk of postmenopausal breast cancer: results of a cohort study and meta‐analysis

The Mediterranean Diet (MD) has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between adherence to MD and risk of postmenopausal breast cancer (and estrogen/progesterone receptor subtypes, ER/PR). In the Netherlands Cohort Study, 62,573 women aged 55–69 years provided information on dietary and lifestyle habits in 1986. Follow‐up for cancer incidence until 2007 (20.3 years) consisted of record linkages with the Netherlands Cancer Registry and the Dutch Pathology Registry PALGA. Adherence to MD was estimated through the alternate Mediterranean Diet Score excluding alcohol. Multivariate case–cohort analyses were based on 2,321 incident breast cancer cases and 1,665 subcohort members with complete data on diet and potential confounders. We also conducted meta‐analyses of our results with those of other published cohort studies. We found a statistically significant inverse association between MD adherence and risk of ER negative (ER?) breast cancer, with a hazard ratio of 0.60 (95% Confidence Interval, 0.39–0.93) for high versus low MD adherence (p _trend = 0.032). MD adherence showed only nonsignificant weak inverse associations with ER positive (ER+) or total breast cancer risk. In meta‐analyses, summary HRs for high versus low MD adherence were 0.94 for total postmenopausal breast cancer, 0.98 for ER+, 0.73 for ER? and 0.77 for ER ? PR? breast cancer. Our findings support an inverse association between MD adherence and, particularly, receptor negative breast cancer. This may have important implications for prevention because of the poorer prognosis of these breast cancer subtypes.     

Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study

The ubiquitous food contaminant cadmium has features of an estrogen mimetic that may promote the development of estrogen-dependent malignancies, such as breast cancer. However, no prospective studies of cadmium exposure and breast cancer risk have been reported. We examined the association between dietary cadmium exposure (at baseline, 1987) and the risk of overall and estrogen receptor (ER)-defined (ER(+) or ER(-)) breast cancer within a population-based prospective cohort of 55,987 postmenopausal women. During an average of 12.2 years of follow-up, 2,112 incident cases of invasive breast cancer were ascertained (1,626 ER(+) and 290 ER(-)). After adjusting for confounders, including consumption of whole grains and vegetables (which account for 40% of the dietary exposure, but also contain putative anticarcinogenic phytochemicals), dietary cadmium intake was positively associated with overall breast cancer tumors, comparing the highest tertile with the lowest [rate ratio (RR), 1.21; 95% confidence interval (CI), 1.07-1.36; P(trend) = 0.02]. Among lean and normal weight women, statistically significant associations were observed for all tumors (RR, 1.27; 95% CI, 1.07-1.50) and for ER(+) tumors (RR, 1.25; 95% CI, 1.03-1.52) and similar, but not statistically significant associations were found for ER(-) tumors (RR, 1.22; 95% CI, 0.76-1.93). The risk of breast cancer increased with increasing cadmium exposure similarly within each tertile of whole grain/vegetable consumption and decreased with increasing consumption of whole grain/vegetables within each tertile of cadmium exposure (P(interaction) = 0.73). Overall, these results suggest a role for dietary cadmium in postmenopausal breast cancer development.     

Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women

Experimental and epidemiological studies suggest that calcium-regulating hormones--parathyroid hormone (PTH) and vitamin D--may be associated with breast cancer risk. No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7,847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders. In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2nd calcium quartile 0.91 (0.65-1.30), in the 3rd quartile 0.89 (0.60-1.31), and in the 4th quartile 0.56 (0.32-0.98), as compared to the 1st calcium quartile. In postmenopausal overweight women (BMI > 25), breast cancer risk was higher in calcium quartiles 2-4 as compared to the 1st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism.     

Modifiable risk factors for advanced vs. early breast cancer in the French E3N cohort

Advanced breast cancer (BC) is associated with heavier treatments and poorer prognosis than early BC. Despite mammographic screening, advanced BC incidence remains stable. Little is known about risk factors differentially associated with advanced BC. We analyzed factors predicting for postmenopausal advanced vs. early BC in the E3N cohort. E3N has been prospectively following 98,995 French women aged 50–65 years at baseline since 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for advanced and early invasive BC were estimated with multivariate Cox competing risk hazard models. With a median follow-up of 15.7 years, 4,941 postmenopausal BC were diagnosed, including 1,878 (38%) advanced BC. Compared to early BC, advanced BC was differentially associated with excess weight (HR 1.39 [95% CI = 1.26–1.53] vs. 1.08 [95% CI = 1.00–1.17], p_homogeneity < 0.0001) and living in a rural area (HR 1.14 [95% CI = 1.00–1.31] vs. 0.93 [95% CI = 0.82–1.04], p_homogeneity 0.02). Excess weight was the only differential risk factor for advanced BC for hormone-dependent BC and for women compliant with screening recommendations. Previous mammography was associated with reduced advanced BC risk (HR 0.86 [95% CI = 0.73–1.00]) and increased early BC risk (HR 1.36 [95% CI = 1.18–1.56], p_homogeneity < 0.0001), but only for hormone-dependent BC. Excess weight appears to be mostly associated with advanced BC, especially hormone-dependent BC. These results add to the evidence for maintaining weight within the recommended limits.     

Adiposity and breast cancer risk in postmenopausal women: Results from the UK Biobank prospective cohort

Body size is an important modifiable risk factor for postmenopausal breast cancer. However, it remains unclear whether direct measures of fat mass are better indicators of risk than anthropometric measures, or whether central adiposity may contribute to risk beyond overall adiposity. We analyzed data from 162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size was measured by trained technicians. Multivariable‐adjusted Cox regression was used to estimate relative risks. Analyses were stratified by age at recruitment, region and socioeconomic status, and adjusted for family history of breast cancer, age at menarche, age at first birth, parity, age at menopause, previous hormone replacement therapy use, smoking, alcohol intake, height, physical activity and ethnicity. We observed 2,913 incident invasive breast cancers during a mean 5.7 years of follow‐up. There was a continuous increase in risk of postmenopausal breast cancer with increasing adiposity, across all measures. The point estimate, comparing women in the top (median 37.6 kg) to bottom (median 17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52–1.90). The magnitudes of the associations between per SD increase in BMI and body fat mass with breast cancer risk were similar, suggesting impedance measures of fat were not substantially better indicators of risk than anthropometric measures. After adjusting for body fat mass, the associations between anthropometric measures of central adiposity and breast cancer risk were attenuated. The magnitude of risk, across all measures of adiposity, was greater in women who had been postmenopausal for 12 or more years.     

Chronic long-term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort

Cadmium, due to its estrogen-like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long-term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System-based metric, which included subject's residence-to-cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (OR_{Q5 vs. Q1} = 0.63; 95% CI: 0.41–0.95, p_trend = 0.043) and for ER−/PR− breast tumors (OR_{Q4 vs. Q1} = 0.62; 95% CI: 0.40–0.95, OR_{Q5 vs. Q1} = 0.68; 95% CI: 0.42–1.07, p_trend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.     

Cardiorespiratory fitness,C-reactive protein and lung cancer risk: A prospective population-based cohort study

BackgroundLittle is known about the joint impact of C-reactive protein (CRP) and cardiorespiratory fitness (CRF) in lung cancer risk. The aim of this study is to examine the joint impact of CRF and CRP in predicting lung cancer risk.MethodsA population-based cohort study of 2276 men with no history of cancer was carried out. Baseline measures of CRP and CRF were divided into median values and categorised. During an average follow-up of 21-years, 73 cases of lung cancer occurred.ResultsIn a multivariate model, men with the combination of high CRP (>50% 1.24 mg/l) and low CRF (maximal oxygen uptake (VO₂max) < 50% 30.08 ml/kg/min) had a fourfold (relative risk (RR) 4.19 95% confidence interval (CI) 1.66–10.57, p < 0.01) risk of lung cancer as compared to the reference group of low CRP (<50% 1.24 mg/l) and high CRF (VO₂max > 50% 30.08 ml/kg/min). Furthermore, men categorised in high CRP and combined with either low/high CRF, had an increased risk for lung cancer as compared to reference group. In further separate independent analysis for CRP and CRF, lung cancer risk was threefold for high CRP (RR 3.22, 95% CI 1.44–7.20, p < 0.01) and low CRF (RR 3.15, 95% CI 1.27–7.78, p = 0.01) as compared to reference CRP (>2.38 mg/l) and CRF (>35.15 ml/kg/min).ConclusionsIn this study, the joint impact of CRP and CRF is a strong risk marker for lung cancer. Furthermore, men with an increase in CRP were at higher risk for lung cancer than men with low CRP and high CRF may reduce the risk.