Skip to main content

Table 1 Smoking status at diagnosisa and colorectal cancer mortality stratified by tumor LINE-1 methylation levels in the Nurses’ Health Study and Health Professionals Follow-up Study

From: Smoking and colorectal cancer survival in relation to tumor LINE-1 methylation levels: a prospective cohort study

 

No. of cases

No. of events

Colorectal cancer-specific mortality

No. of events

Overall mortality

Multivariable

HRb,c (95% CI)

Multivariable

HRb,c (95% CI)

LINE-1 methylation level

< 60% (low)

 Never smoker

167

53

1 (referent)

110

1 (referent)

 Past smoker

  < 19 packyears

94

35

1.05 (0.66–1.68)

56

0.91 (0.64–1.31)

  ≥ 20 packyears

103

37

1.16 (0.75–1.81)

75

1.17 (0.84–1.62)

 Current smoker

37

19

1.55 (0.94–2.56)

32

1.80 (1.19–2.73)

 Ptrendd

  

0.14

 

0.024

LINE-1 methylation level

60–67.9% (intermediate)

 Never smoker

161

43

1 (referent)

101

1 (referent)

 Past smoker

  < 19 packyears

98

20

0.54 (0.30–0.95)

55

0.66 (0.47–0.93)

  ≥ 20 packyears

100

28

0.68 (0.42–1.10)

77

0.95 (0.70–1.28)

 Current smoker

44

14

0.77 (0.37–1.59)

35

1.01 (0.64–1.60)

 Ptrendcd

  

0.24

 

0.91

LINE-1 methylation level

≥ 68% (high)

 Never smoker

156

44

1 (referent)

93

1 (referent)

 Past smoker

  < 19 packyears

93

16

0.83 (0.44–1.57)

44

0.89 (0.60–1.32)

  ≥ 20 packyears

111

21

0.77 (0.47–1.24)

68

0.92 (0.68–1.25)

 Current smoker

44

13

0.93 (0.50–1.73)

30

1.33 (0.85–2.08)

 Ptrendd

  

0.55

 

0.47

 Pinteractione

  

0.017

 

0.050

  1. Abbreviations: CI confidence interval, HR hazard ratio, LINE-1 long interspersed nucleotide element-1
  2. aAs most current smokers (86%) had a smoking history of ≥20 packyears at diagnosis, we did not examine associations by packyears of smoking in current smokers. Of the 599 past smokers, 285 (47.6%) had a smoking history of 1–19 packyears and 314 cases (52.4%) had a history of ≥20 packyears. Past smokers who quit ≥10 years prior to diagnosis were more likely to have a smoking history of 1–19 packyears than those who quit <10 years prior to diagnosis (201 out of 322 or 62% vs. 84 out of 277 or 30%); therefore, for past smokers, we did not further stratify by time since quitting smoking (Additional file 1: Supplementary Table 1)
  3. bInverse probability weighting was applied to reduce selection bias due to tissue data availability
  4. cThe multivariable Cox regression model initially included age, sex, year of diagnosis, family history of colorectal cancer, body mass index, alcohol consumption at diagnosis, empirical dietary inflammatory pattern (EDIP) score at diagnosis, dietary fiber intake at diagnosis, folate intake at diagnosis, regular aspirin intake at diagnosis, physical activity status at diagnosis, tumor location, tumor differentiation, microsatellite instability, CpG island methylator phenotype, KRAS mutation, BRAF mutation, and PIK3CA mutation. A backward elimination with a threshold of P = 0.05 was used to select variables in the final models
  5. dThe trend test was conducted using an ordinal smoking variable (never smoker [0], past smoker with 1–19 packyears [1], past smoker with ≥20 packyears [2], and current smoker [3])
  6. ePinteraction was calculated using the Wald test for the cross-product term of smoking status at diagnosis [ordinal; never smoker, past smoker (<19 packyears, ≥20 packyears), current smoker] and LINE-1 methylation level (continuous) in Cox regression models
Back to article page

Epigenetics Communications

ISSN: 2730-7034